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Antibiotics, Volume 9, Issue 6 (June 2020) – 85 articles

Cover Story (view full-size image): Invasive fungal infections still constitute a major health problem, especially when affecting immunocompromised patients. A microbial natural products research program focused on the discovery of new antifungal compounds led to the identification and isolation of TKR 2999 from cultures of the fungus Foliophoma fallens, isolated from Pinus sp. using a dilution to extinction method. The structure of this lipodepsipeptide has been solved by spectroscopic and chemical methods and disclosed more than 20 years after its first report in a Japanese patent. The potent antifungal bioactivity of the molecule against Candida and Aspergillus species, the main pathogens causing fungal infections, has also been confirmed in our studies. Based on our results, Foliophoma has been identified as a genus to be added to the extensive list of fungal genera which are producers of interesting bioactive [...] Read more.
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Article
N-Nonyloxypentyl-l-Deoxynojirimycin Inhibits Growth, Biofilm Formation and Virulence Factors Expression of Staphylococcus aureus
Antibiotics 2020, 9(6), 362; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060362 - 26 Jun 2020
Cited by 4 | Viewed by 854
Abstract
Staphylococcus aureus is one of the major causes of hospital- and community-associated bacterial infections throughout the world, which are difficult to treat due to the rising number of drug-resistant strains. New molecules displaying potent activity against this bacterium are urgently needed. In this [...] Read more.
Staphylococcus aureus is one of the major causes of hospital- and community-associated bacterial infections throughout the world, which are difficult to treat due to the rising number of drug-resistant strains. New molecules displaying potent activity against this bacterium are urgently needed. In this study, d- and l-deoxynojirimycin (DNJ) and a small library of their N-alkyl derivatives were screened against S. aureus ATCC 29213, with the aim to identify novel candidates with inhibitory potential. Among them, N-nonyloxypentyl-l-DNJ (l-NPDNJ) proved to be the most active compound against S. aureus ATCC 29213 and its clinical isolates, with the minimum inhibitory concentration (MIC) value of 128 μg/mL. l-NPDNJ also displayed an additive effect with gentamicin and oxacillin against the gentamicin- and methicillin-resistant S. aureus isolate 00717. Sub-MIC values of l-NPDNJ affected S. aureus biofilm development in a dose-dependent manner, inducing a strong reduction in biofilm biomass. Moreover, real-time reverse transcriptase PCR analysis revealed that l-NPDNJ effectively inhibited at sub-MIC values the transcription of the spa, hla, hlb and sea virulence genes, as well as the agrA and saeR response regulator genes. Full article
(This article belongs to the Special Issue Novel Strategies to Control Antimicrobial Resistance)
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Article
In Vitro Azole and Amphotericin B Susceptibilities of Malassezia furfur from Bloodstream Infections Using E-Test and CLSI Broth Microdilution Methods
Antibiotics 2020, 9(6), 361; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060361 - 26 Jun 2020
Cited by 2 | Viewed by 869
Abstract
The number of reports of Malassezia furfur bloodstream infections is constantly increasing and there is a need for more simple antifungal susceptibility methods for their management. In this study, a total of 39 M. furfur isolates collected from hospitalized patients with fungemia were [...] Read more.
The number of reports of Malassezia furfur bloodstream infections is constantly increasing and there is a need for more simple antifungal susceptibility methods for their management. In this study, a total of 39 M. furfur isolates collected from hospitalized patients with fungemia were screened for antifungal susceptibility to azole and amphotericin B (AmB) using Clinical and Laboratory Standards Institute broth microdilution (CLSI BMD) and E-test in Sabouraud dextrose agar + 1% Tween80 (SDAt) and mDixon agar (DIX). Essential agreement (EA) and discrepancies between the two methods were evaluated after 48 h and 72 h reading times. Itraconazole (ITZ) and posaconazole (POS) displayed the lowest MIC values whereas fluconazole (FLZ) and AmB the highest, regardless of the methods and the reading time. The EA between BMD was >95% for FLZ and voriconazole (VOR) regardless of the media in the E-tests and reading time. The EA between BMD with E-test for AmB was >97% only when E-test in SDAt was used. The EA between BMD and E-test for ITZ and POS varied according to the media in E-test procedures and the reading time and was higher than 66.6% (POS) or 72% (ITZ) only when SABt was used. Substantial discrepancies for ITZ and POS were >5.1% regardless of the media and the reading time. This study suggests that the E-test in SABt represents an alternative method to CLSI BMD to evaluate the susceptibility of M. furfur to FLZ, VOR and AmB and not for ITZ and POS. Full article
Article
Development of a Tailored, Complex Intervention for Clinical Reflection and Communication about Suspected Urinary Tract Infections in Nursing Home Residents
Antibiotics 2020, 9(6), 360; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060360 - 25 Jun 2020
Cited by 2 | Viewed by 1415
Abstract
Background: Inappropriate antibiotic treatments for urinary tract infections (UTIs) in nursing homes cause the development of resistant bacteria. Nonspecific symptoms and asymptomatic bacteriuria are drivers of overtreatment. Nursing home staff provide general practice with information about ailing residents; therefore, their knowledge and communication [...] Read more.
Background: Inappropriate antibiotic treatments for urinary tract infections (UTIs) in nursing homes cause the development of resistant bacteria. Nonspecific symptoms and asymptomatic bacteriuria are drivers of overtreatment. Nursing home staff provide general practice with information about ailing residents; therefore, their knowledge and communication skills influence prescribing. This paper describes the development of a tailored, complex intervention for a cluster-randomised trial that targets the knowledge of UTI and communication skills in nursing home staff to reduce antibiotic prescriptions. Methods: A dialogue tool was drafted, drawing on participatory observations in nursing homes, interviews with stakeholders, and a survey in general practice. The tool was tailored through a five-phase process that included stakeholders. Finally, the tool and a case-based educational session were tested in a pilot study. Results: The main barriers were that complex patients were evaluated by healthcare staff with limited knowledge about disease and clinical reasoning; findings reported to general practice were insignificant and included vague descriptions; there was evidence of previous opinion bias; nonspecific symptoms were interpreted as UTI; intuitive reasoning led to the inappropriate suspicion of UTI. Conclusion: Sustainable change in antibiotic-prescribing behaviour in nursing homes requires a change in nursing home staff’s beliefs about and management of UTIs. Full article
(This article belongs to the Special Issue Antimicrobial Stewardship in Primary Care)
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Article
Determination of Delafloxacin in Pharmaceutical Formulations Using a Green RP-HPTLC and NP-HPTLC Methods: A Comparative Study
Antibiotics 2020, 9(6), 359; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060359 - 25 Jun 2020
Cited by 9 | Viewed by 818
Abstract
In this work; delafloxacin (DLFX) was determined using a validated green RP-HPTLC and NP-HPTLC methods in commercial tablets and in-house developed solid lipid nanoparticles (SLNs). RP-HPTLC determination of DLFX was performed using “RP-18 silica gel 60 F254S HPTLC plates”. However; NP-HPTLC estimation of [...] Read more.
In this work; delafloxacin (DLFX) was determined using a validated green RP-HPTLC and NP-HPTLC methods in commercial tablets and in-house developed solid lipid nanoparticles (SLNs). RP-HPTLC determination of DLFX was performed using “RP-18 silica gel 60 F254S HPTLC plates”. However; NP-HPTLC estimation of DLFX was performed using “silica gel 60 F254S HPTLC plates”. For a green RP-HPTLC method; the ternary combination of ethanol:water:ammonia solution (5:4:2 v/v/v) was used as green mobile phase. However; for NP-HPTLC method; the ternary mixture of ethyl acetate: methanol: ammonia solution (5:4:2 v/v/v) was used as normal mobile phase. The analysis of DLFX was conducted in absorbance/reflectance mode of densitometry at λmax = 295 nm for both methods. RP-HPTLC method was found more accurate, precise, robust and sensitive for the analysis of DLFX compared with the NP-HPTLC method. The % assay of DLFX in commercial tablets and in-house developed SLNs was determined as 98.2 and 101.0%, respectively, using the green RP-HPTLC technique, however; the % assay of DLFX in commercial tablets and in-house developed SLNs was found to be 94.4 and 95.0%, respectively, using the NP-HPTLC method. Overall, the green RP-HPTLC method was found superior over the NP-HPTLC. Therefore, the proposed green RP-HPTLC method can be successfully applied for analysis of DLFX in commercial tablets, SLNs and other formulations containing DLFX. Full article
(This article belongs to the Special Issue Challenges in Antibiotics Analysis)
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Article
Anti-Bacterial Effects of Essential Oils against Uropathogenic Bacteria
Antibiotics 2020, 9(6), 358; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060358 - 25 Jun 2020
Cited by 3 | Viewed by 1339
Abstract
Given the increasing antimicrobial resistance in urinary tract infections (UTI), alternative strategies need to be investigated. Determination of minimal inhibitory and bactericidal concentrations of essential oils from cajeput, lemongrass, tea tree, and thyme in artificial urine, revealed bactericidal activity of all four tested [...] Read more.
Given the increasing antimicrobial resistance in urinary tract infections (UTI), alternative strategies need to be investigated. Determination of minimal inhibitory and bactericidal concentrations of essential oils from cajeput, lemongrass, tea tree, and thyme in artificial urine, revealed bactericidal activity of all four tested essential oils against seven uropathogenic species with values ranging between 0.78–50 mg/mL. Tea tree and thyme essential oils were more efficient than lemongrass and cajeput. In addition, antibiotic-resistant strains showed similar susceptibility as antibiotic-sensitive strains, suggesting no cross-resistance between antibiotics and these essential oils. Checkerboard assays revealed a synergistic activity of the combination of thyme and tea tree. Furthermore, the combination with thyme and tea tree essential oils increased the activity of fosfomycin and pivmecillinam, but not nitrofurantoin, against Escherichia coli. This study provides a basis for further investigation of the potential of thyme and tea tree oil as an alternative or additional treatment of UTI. Full article
(This article belongs to the Special Issue Antibacterial Activity of Plant Extracts and Essential Oils)
Article
Perioperative Antibiotic Prophylaxis: Knowledge and Attitudes among Resident Physicians in Italy
Antibiotics 2020, 9(6), 357; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060357 - 25 Jun 2020
Cited by 3 | Viewed by 708
Abstract
The aim of this study is to evaluate knowledge and attitudes on the perioperative antibiotic prophylaxis (PAP) among surgery and anesthesiology resident physicians in Italy. A Web-based national survey of Italian surgery and anesthesiology resident physicians was conducted between March 2018 and January [...] Read more.
The aim of this study is to evaluate knowledge and attitudes on the perioperative antibiotic prophylaxis (PAP) among surgery and anesthesiology resident physicians in Italy. A Web-based national survey of Italian surgery and anesthesiology resident physicians was conducted between March 2018 and January 2019. Participants completed a questionnaire and three case vignettes for each specialty. Of the 1282 resident physicians selected, 466 completed the online questionnaire for a response rate of 36.3%. More than half of the sample were female (52.9%), and the mean age was 30 years. A total of 36.3% of the participants had an adequate knowledge score about PAP. Multiple logistic regression analysis showed that resident physicians in general surgery compared to those in anesthesiology, those who agreed that PAP must be performed within 60 min before surgical incision, and those who were aware regarding the availability about the availability of national guidelines on PAP, were significantly more likely to have adequate knowledge about PAP. Moreover, 14% of participants were very concerned that patients may contract surgical site infections during hospitalization. These findings should be useful to promote educational intervention specifically targeted for surgery and anesthesiology resident physicians organizing training course on PAP, to improve the correct antibiotic use and to prevent healthcare-associated infections. Full article
Brief Report
Structural Modifications of 3-Triazeneindoles and Their Increased Activity Against Mycobacterium tuberculosis
Antibiotics 2020, 9(6), 356; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060356 - 24 Jun 2020
Viewed by 831
Abstract
We synthesized 100 novel indole-based compounds with polyaza-functionalities, including 3-triazeneindoles, and tested their activity in vitro against laboratory M. tuberculosis H37Rv and clinical izoniazid-resistant CN-40 isolates, using gross and fine titration approaches. Here we present a few 3-triazeneindoles with the highest anti-mycobacterial activity. [...] Read more.
We synthesized 100 novel indole-based compounds with polyaza-functionalities, including 3-triazeneindoles, and tested their activity in vitro against laboratory M. tuberculosis H37Rv and clinical izoniazid-resistant CN-40 isolates, using gross and fine titration approaches. Here we present a few 3-triazeneindoles with the highest anti-mycobacterial activity. Introduction of short lipid tails into the 3-triazeneindole core additionally increased their activity against mycobacteria engulfed by murine macrophages. We also demonstrate that the compound TU112, one of the most active in our previous study, being not bioavailable after administration in mice per os, manifests prominent anti-mycobacterial activity after intravenous or aerosol delivery, as assessed by the mouse serum and lung supernatant titration assays. Full article
(This article belongs to the Special Issue Mycobacterial Infections and Therapy)
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Communication
Helicobacter pylori Biofilm Confers Antibiotic Tolerance in Part via A Protein-Dependent Mechanism
Antibiotics 2020, 9(6), 355; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060355 - 24 Jun 2020
Cited by 5 | Viewed by 1387
Abstract
Helicobacter pylori, a WHO class I carcinogen, is one of the most successful human pathogens colonizing the stomach of over 4.4 billion of the world’s population. Antibiotic therapy represents the best solution but poor response rates have hampered the elimination of H. [...] Read more.
Helicobacter pylori, a WHO class I carcinogen, is one of the most successful human pathogens colonizing the stomach of over 4.4 billion of the world’s population. Antibiotic therapy represents the best solution but poor response rates have hampered the elimination of H. pylori. A growing body of evidence suggests that H. pylori forms biofilms, but the role of this growth mode in infection remains elusive. Here, we demonstrate that H. pylori cells within a biofilm are tolerant to multiple antibiotics in a manner that depends partially on extracellular proteins. Biofilm-forming cells were tolerant to multiple antibiotics that target distinct pathways, including amoxicillin, clarithromycin, and tetracycline. Furthermore, this tolerance was significantly dampened following proteinase K treatment. These data suggest that H. pylori adapts its phenotype during biofilm growth resulting in decreased antibiotic susceptibility but this tolerance can be partially ameliorated by extracellular protease treatment. Full article
(This article belongs to the Special Issue Antibiotic Tolerance of Bacterial Biofilms)
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Article
Antifungal In Vitro Activity of Pilosulin- and Ponericin-Like Peptides from the Giant Ant Dinoponera quadriceps and Synergistic Effects with Antimycotic Drugs
Antibiotics 2020, 9(6), 354; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060354 - 23 Jun 2020
Cited by 3 | Viewed by 967
Abstract
Venoms from ants comprise a rich source of bioactive peptides, including antimicrobial peptides. From the proteome and peptidome of the giant ant Dinoponera quadriceps venom, members of five known classes of antimicrobial peptides were disclosed (e.g., dermaseptin-, defensin-, ICK-, pilosulin- and ponericin-like types). [...] Read more.
Venoms from ants comprise a rich source of bioactive peptides, including antimicrobial peptides. From the proteome and peptidome of the giant ant Dinoponera quadriceps venom, members of five known classes of antimicrobial peptides were disclosed (e.g., dermaseptin-, defensin-, ICK-, pilosulin- and ponericin-like types). Based on comparative analysis, these family members have structural determinants that indicate they could display antimicrobial activities. In previous works, pilosulin- and ponericin-like peptides were demonstrated to be active against bacteria, fungi, and parasites. Herein, the antifungal activity of ponericin- and pilosulin-like peptides were assessed, aiming at the expansion of the knowledge about AMPs in predatory ants and the development of new microbicide strategies to deal with difficult-to-treat fungal infections. Synthetic pilosulin- (Dq-2562, Dq-1503, and Dq-1319) and ponericin-like (Dq-3162) peptides were evaluated for their fungicide and fungistatic activities against different species of Candida, including a drug-resistant clinical strain. The MICs and MLCs were determined for all peptides individually and in combination with general antifungal drugs by the microdilution method. The time-kill kinetic curves were set up by means of a luminescent reagent, of which the light signal is proportional to the number of viable cells. The candicidal synergism observed by the combination of subinhibitory concentrations of peptides and general antimycotic drugs were quantified by the checkerboard test and fluorescent dye permeation assay. The influence of ergosterol on the antifungal activity was verified by supplementation of culture medium. The pilosulin- (Dq-2562 and Dq-1503) and ponericin-like (Dq-3162) were the most active peptides, displaying a broad spectrum of antifungal activity in vitro, with MICs in the range of 0.625 to 10 µM. The combination of peptides and conventional antimycotic drugs displayed a synergistic reduction in the MIC values of individual peptides and drugs, while soluble ergosterol in the culture medium increased the MICs. The fungicide and fungistatic activity of the individual peptides and peptides in combination with antimycotics were time-dependent with a rapid onset of action and long-lasting effect, which involved membrane disruption as an underlying mechanism of their action. Altogether, pilosulin- and ponericin-like peptides from the giant ant D. quadriceps venom display a broad-spectrum of candicidal activity, what allows their inclusion in the row of the antifungal peptides and gives support for further studies on the development of strategies to fight candidiasis. Full article
(This article belongs to the Special Issue Peptide Antibiotics from Microbes and Venomous Animals)
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Review
Bioactive Compounds, Pharmacological Actions, and Pharmacokinetics of Wormwood (Artemisia absinthium)
Antibiotics 2020, 9(6), 353; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060353 - 23 Jun 2020
Cited by 14 | Viewed by 2213
Abstract
Plants have been used since ancient times to cure certain infectious diseases, and some of them are now standard treatments for several diseases. Due to the side effects and resistance of pathogenic microorganisms to antibiotics and most drugs on the market, a great [...] Read more.
Plants have been used since ancient times to cure certain infectious diseases, and some of them are now standard treatments for several diseases. Due to the side effects and resistance of pathogenic microorganisms to antibiotics and most drugs on the market, a great deal of attention has been paid to extracts and biologically active compounds isolated from plant species used in herbal medicine. Artemisia absinthium is an important perennial shrubby plant that has been widely used for the treatment of several ailments. Traditionally, A. absinthium has always been of pharmaceutical and botanical importance and used to manage several disorders including hepatocyte enlargement, hepatitis, gastritis, jaundice, wound healing, splenomegaly, dyspepsia, indigestion, flatulence, gastric pain, anemia, and anorexia. It has also been documented to possess antioxidant, antifungal, antimicrobial, anthelmintic, anti-ulcer, anticarcinogenic, hepatoprotective, neuroprotective, antidepressant, analgesic, immunomodulatory, and cytotoxic activity. Long-term use of A. absinthium essential oil may cause toxic and mental disorders in humans with clinical manifestations including convulsions, sleeplessness, and hallucinations. Combination chemotherapies of artemisia extract or its isolated active constituents with the currently available antibabesial or anti-malarial drugs are now documented to relieve malaria and piroplasmosis infections. The current review examines the phytoconstituents, toxic and biological activities of A. absinthium. Full article
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Article
Isolation and Characterization of Pectobacterium Phage vB_PatM_CB7: New Insights into the Genus Certrevirus
Antibiotics 2020, 9(6), 352; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060352 - 21 Jun 2020
Cited by 5 | Viewed by 1459
Abstract
To date, Certrevirus is one of two genera of bacteriophage (phage), with phages infecting Pectobacterium atrosepticum, an economically important phytopathogen that causes potato blackleg and soft rot disease. This study provides a detailed description of Pectobacterium phage CB7 (vB_PatM_CB7), which specifically infects [...] Read more.
To date, Certrevirus is one of two genera of bacteriophage (phage), with phages infecting Pectobacterium atrosepticum, an economically important phytopathogen that causes potato blackleg and soft rot disease. This study provides a detailed description of Pectobacterium phage CB7 (vB_PatM_CB7), which specifically infects P. atrosepticum. Host range, morphology, latent period, burst size and stability at different conditions of temperature and pH were examined. Analysis of its genome (142.8 kbp) shows that the phage forms a new species of Certrevirus, sharing sequence similarity with other members, highlighting conservation within the genus. Conserved elements include a putative early promoter like that of the Escherichia coli sigma70 promoter, which was found to be shared with other genus members. A number of dissimilarities were observed, relating to DNA methylation and nucleotide metabolism. Some members do not have homologues of a cytosine methylase and anaerobic nucleotide reductase subunits NrdD and NrdG, respectively. Furthermore, the genome of CB7 contains one of the largest numbers of homing endonucleases described in a single phage genome in the literature to date, with a total of 23 belonging to the HNH and LAGLIDADG families. Analysis by RT-PCR of the HNH homing endonuclease residing within introns of genes for the large terminase, DNA polymerase, ribonucleotide reductase subunits NrdA and NrdB show that they are splicing competent. Electrospray ionization-tandem mass spectrometry (ESI-MS/MS) was also performed on the virion of CB7, allowing the identification of 26 structural proteins—20 of which were found to be shared with the type phages of the genera of Vequintavirus and Seunavirus. The results of this study provide greater insights into the phages of the Certrevirus genus as well as the subfamily Vequintavirinae. Full article
(This article belongs to the Special Issue Phage Diversity for Research and Application)
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Article
Chalcones Isolated from Arrabidaea brachypoda Flowers as Inhibitors of NorA and MepA Multidrug Efflux Pumps of Staphylococcus aureus
Antibiotics 2020, 9(6), 351; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060351 - 20 Jun 2020
Cited by 7 | Viewed by 1202
Abstract
Bacterial resistance to antibiotics has become a public health issue around the world. The present study aimed to evaluate the antibacterial activity of chalcones isolated from flowers of Arrabidaea brachypoda, and their potential as efflux pump inhibitors of Staphylococcus aureus efflux pumps. [...] Read more.
Bacterial resistance to antibiotics has become a public health issue around the world. The present study aimed to evaluate the antibacterial activity of chalcones isolated from flowers of Arrabidaea brachypoda, and their potential as efflux pump inhibitors of Staphylococcus aureus efflux pumps. Microdilution assays were performed with natural products from A. brachypoda. Chalcones 1, 3, 4, and 5 did not show intrinsic antimicrobial activity against all S. aureus strains tested, but they were able to potentiate the Norfloxacin action against the SA1199-B (norA) strain, with a better modulating action for the 4 trimethoxylated chalcone. All chalcones were also able to potentiate the action of EtBr against SA1199-B strain, suggesting a potential NorA inhibition. Moreover, chalcone 4 was able to interfere in the activity of MepA, and interfered weakly in the QacA/B activity. Molecular docking analyzes showed that tested chalcones are capable of binding in the hydrophobic cavity of NorA and MepA, in the same Norfloxacin binding site, indicating that chalcone 4 compete with the antibiotic for the same NorA and MepA binding sites. Association of chalcone 4 with Norfloxacin could be an alternative against multidrug resistant S. aureus over-productive of NorA or MepA. Full article
(This article belongs to the Special Issue The Role of Efflux Pump Inhibitor in Bacterial Multidrug Resistance)
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Article
Crystallography, in Silico Studies, and In Vitro Antifungal Studies of 2,4,5 Trisubstituted 1,2,3-Triazole Analogues
Antibiotics 2020, 9(6), 350; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060350 - 20 Jun 2020
Cited by 3 | Viewed by 1176
Abstract
A series of 2,4,5 trisubstituted-1,2,3-triazole analogues have been screened for their antifungal activity against five fungal strains, Candida parapsilosis, Candida albicans, Candida tropicalis, Aspergillus niger, and Trichophyton rubrum, via a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) microdilution assay. Compounds GKV10, GKV11, [...] Read more.
A series of 2,4,5 trisubstituted-1,2,3-triazole analogues have been screened for their antifungal activity against five fungal strains, Candida parapsilosis, Candida albicans, Candida tropicalis, Aspergillus niger, and Trichophyton rubrum, via a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) microdilution assay. Compounds GKV10, GKV11, and GKV15 emerged as promising antifungal agents against all the fungal strains used in the current study. One of the highly active antifungal compounds, GKV10, was selected for a single-crystal X-ray diffraction analysis to unequivocally establish its molecular structure, conformation, and to understand the presence of different intermolecular interactions in its crystal lattice. A cooperative synergy of the C-H···O, C-H···N, C-H···S, C-H···π, and π···π intermolecular interactions was present in the crystal structure, which contributed towards the overall stabilization of the lattice. A molecular docking study was conducted for all the test compounds against Candida albicans lanosterol-14α-demethylase (pdb = 5 tzl). The binding stability of the highly promising antifungal test compound, GKV15, from the series was then evaluated by molecular dynamics studies. Full article
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Article
University Students’ Antibiotic Use and Knowledge of Antimicrobial Resistance: What Are the Common Myths?
Antibiotics 2020, 9(6), 349; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060349 - 20 Jun 2020
Cited by 3 | Viewed by 1516
Abstract
We aimed to assess antibiotic usage and knowledge regarding antibiotics and antimicrobial resistance (AMR) among undergraduate students of the Universiti Brunei Darussalam (UBD), public university located in Brunei Darussalam. A cross-sectional study was performed using a self-administered questionnaire. The questionnaire was adapted from [...] Read more.
We aimed to assess antibiotic usage and knowledge regarding antibiotics and antimicrobial resistance (AMR) among undergraduate students of the Universiti Brunei Darussalam (UBD), public university located in Brunei Darussalam. A cross-sectional study was performed using a self-administered questionnaire. The questionnaire was adapted from the World Health Organization’s (WHO) “Antibiotic resistance: Multi-country public awareness” survey distributed online. Students at the UBD were invited to participate in the online survey through internal email. The questionnaire consisted of five sections: demographic information, antibiotic usage, knowledge on antibiotics, antibiotic resistance (AMR), and use of antibiotics in agriculture. The data were analyzed descriptively and appropriate inferential statistics were used accordingly. A total of 130 students returned a completed questionnaire. The result of the study found that 51% (n = 66) of the students had good level of knowledge of antibiotic and antimicrobial resistance with a mean total knowledge score of nine out of 14. Of note, 76% (n = 99) of the respondents mistakenly believed that antibiotic resistance is the result of the body becoming resistant to antibiotics. Only 14% (n = 18) of the respondents were found to have poor knowledge on antibiotics and antimicrobial resistance in the study. Misconceptions in regards to the use of antibiotics for conditions related to viral illnesses like cold and flu (41%, n = 53) were noticed among the respondents in our study. Thus, improving knowledge on antibiotics is crucial to address these beliefs. Full article
(This article belongs to the Special Issue Surveillance of Antimicrobial Use on Different Levels)
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Article
Label-Free Electrochemical Microfluidic Chip for the Antimicrobial Susceptibility Testing
Antibiotics 2020, 9(6), 348; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060348 - 20 Jun 2020
Cited by 4 | Viewed by 1203
Abstract
The emergence and spread of antibiotic-resistant bacteria is a global threat to human health. An accurate antibiotic susceptibility test (AST) before initiating the treatment is paramount in the treatment and bacterial resistance control. However, the current AST methods either are complex, use chemical [...] Read more.
The emergence and spread of antibiotic-resistant bacteria is a global threat to human health. An accurate antibiotic susceptibility test (AST) before initiating the treatment is paramount in the treatment and bacterial resistance control. However, the current AST methods either are complex, use chemical and biological labels, lack multiplexing, are expensive, or are too slow to be used for routine screening. The primary objective of the current study is to develop an automated electrochemical microfluidic chip (EMC) for simple and rapid AST. The microfluidic channels and gold microelectrodes were designed for the automation of antibiotic mixing and distribution in multiple test chambers and for electrical signal measurements. The designed chip was tested for AST with E. coli samples, and the results were compared with conventional broth microdilution. The presented EMC provided rapid bacterial count and AST in 170 and 150 min, respectively, while the conventional broth microdilution evaluates in 450 and 240 min, respectively. The rapid AST capability of the EMC was further demonstrated with the artificial urine samples, and the results were obtained in 270 min, which was 90 min faster than the broth microdilution method. Additionally, the minimum inhibitory concentration (MIC) was evaluated on the EMC and compared with the results from an AlamarBlue assay. The experimental results indicate the sensitivity of the chip, minimum loss of antibiotics, and eventually, reduction in the evolution of antibiotic resistance. Cumulatively, we have developed an automated, label-free, economical, rapid, robust, and user-friendly EMC for the evaluation of AST in urine samples. Full article
(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)
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Article
Antibacterial Properties of Nano-Ag Coating on Healing Abutment: An In Vitro and Clinical Study
Antibiotics 2020, 9(6), 347; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060347 - 19 Jun 2020
Cited by 3 | Viewed by 984
Abstract
Peri-implantitis is an inflammatory disease with a relevant focus on the long-term success of dental implants and implant-supported prostheses. The present study focuses on the antibacterial effect of the silver nanoparticle and investigated the suppression of dental plaque adhesion on implant abutment and/or [...] Read more.
Peri-implantitis is an inflammatory disease with a relevant focus on the long-term success of dental implants and implant-supported prostheses. The present study focuses on the antibacterial effect of the silver nanoparticle and investigated the suppression of dental plaque adhesion on implant abutment and/or superstructure by micro-wave assistant nanosilver coating in vivo and in vitro. Nanosilver coating on pure titanium was prepared by microwave-assisted synthesis, and characterized by scanning electron microscopy and energy-dispersive X-ray spectroscopy. In vitro studies were conducted to analyze biocompatibility using MTS assay and fluorescence microscopy with human gingival fibroblasts to evaluate antibacterial activity. During the in vivo study, nanosilver coating was applied to the healing abutments, and the prevention of plaque accumulation on nanosilver coating was confirmed by a split-mouth randomized clinical trial. The aggregation of nano-sized particles was found on the titanium surface with an antibacterial effect. The coating had no cytotoxic effect on human gingival fibroblasts. The result of the clinical trial showed that the coating suppressed the dental plaque adhesion on the healing abutments. Nanosilver coating is a promising material with antibacterial properties and can be used for implant abutments and prostheses for preventing peri-implantitis. Full article
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Editorial
Humans, Animals, Food and Environment: One Health Approach against Global Antimicrobial Resistance
Antibiotics 2020, 9(6), 346; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060346 - 19 Jun 2020
Viewed by 1072
Abstract
Antimicrobial resistance represents one of the most relevant threats to global public health and food security, affecting anyone, of any age, in any country and is responsible for longer hospital stays, higher medical costs and increased mortality. Resistant microorganisms are present in humans, [...] Read more.
Antimicrobial resistance represents one of the most relevant threats to global public health and food security, affecting anyone, of any age, in any country and is responsible for longer hospital stays, higher medical costs and increased mortality. Resistant microorganisms are present in humans, animals, food and the environment, and, therefore, the One Health approach is very promising to counteract antimicrobial resistance, since human health and animal health are connected to each other and with the environment and the latter a potential source of resistant microorganisms. In this context, the need for novel antimicrobial drugs has stimulated the exploration of plant products as a source of novel phytotherapeutics able to reverse antimicrobial resistance when used in combination with conventional antibiotic drugs. Full article
(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals)
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Article
Clinical Findings and Antimicrobial Susceptibility of Anaerobic Bacteria Isolated in Bloodstream Infections
Antibiotics 2020, 9(6), 345; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060345 - 19 Jun 2020
Cited by 3 | Viewed by 902
Abstract
The objectives of this study were to report on the antimicrobial susceptibility of 141 clinically significant anaerobic bacteria isolated from bloodstream infections between January 2016 and April 2020 in a tertiary-care hospital in Granada (Spain) and to describe the main clinical features of [...] Read more.
The objectives of this study were to report on the antimicrobial susceptibility of 141 clinically significant anaerobic bacteria isolated from bloodstream infections between January 2016 and April 2020 in a tertiary-care hospital in Granada (Spain) and to describe the main clinical features of the patients. Species identification was performed by MALDI-TOF MS (Bruker Daltonics, Billerica, MA, USA). Antimicrobial susceptibility tests were performed against penicillin, amoxicillin-clavulanic acid, imipenem, moxifloxacin, clindamycin, metronidazole, and piperacillin-tazobactam using the gradient diffusion technique and EUCAST breakpoints, except for moxifloxacin (CLSI breakpoints). The most frequent anaerobes were Bacteroides (43.9%, n = 62), Clostridium (24.1%, n = 34) and Gram-positive anaerobic cocci (GPACs) (15.6%, n = 22). Almost all tested anaerobes were susceptible to imipenem and amoxicillin-clavulanic acid, except for Bacteroides. High overall resistance rates to clindamycin were observed, especially for Gram-positive anaerobic cocci (GPACs) (54.5%) and for Bacteroides spp. (45.1%). Overall, low resistance rates to almost all antibiotics were observed for Clostridium. High resistance rates to penicillin were also observed for Gram-positive anaerobic bacilli (GPABs) (44.4%), as well as to metronidazole (22.2%), although only nine isolates were included. Antimicrobial susceptibility testing for anaerobes should always be performed in severe infections, such as those localized in the bloodstream. The information obtained contributes to selecting empirical treatments according with local data on resistance. Full article
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Article
In Vitro Efficacy of Essential Oils from Melaleuca Alternifolia and Rosmarinus Officinalis, Manuka Honey-based Gel, and Propolis as Antibacterial Agents Against Canine Staphylococcus Pseudintermedius Strains
Antibiotics 2020, 9(6), 344; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060344 - 19 Jun 2020
Cited by 1 | Viewed by 1056
Abstract
Essential oils (EOs) and honeybee products (e.g., honey and propolis) are natural mixtures of different volatile compounds that are frequently used in traditional medicine and for pathogen eradication. The aim of this study was to evaluate the antibacterial properties of tea tree ( [...] Read more.
Essential oils (EOs) and honeybee products (e.g., honey and propolis) are natural mixtures of different volatile compounds that are frequently used in traditional medicine and for pathogen eradication. The aim of this study was to evaluate the antibacterial properties of tea tree (Melaleuca alternifolia) EO (TTEO), Rosmarinus officinalis EO (ROEO), manuka-based gel, and propolis against 23 strains of Staphylococcus pseudintermedius (SP) isolated from canine pyoderma. Antimicrobial resistance screening was assessed using a panel of nine antimicrobial agents coupled with a PCR approach. An aromatogram was done for both EOs, using the disk diffusion method. The minimum inhibitory concentration (MIC) was determined for all the compounds. Among the 23 SP strains, 14 (60.9%) were multidrug-resistant (MDR), 11 strains (47.8%) were methicillin-resistant (MRSP), and 9 (39.1%) were non-MDR. The mean diameter of the inhibition zone for Melaleuca and Rosmarinus were 24.5 ± 8.8 mm and 15.2 ± 8.9 mm, respectively, resulting as statistically different (p = 0.0006). MIC values of TTEO and ROEO were similar (7.6 ± 3.2% and 8.9 ± 2.1%, respectively) and no statistical significances were found. Honeybee products showed lower MIC compared to those of EOs, 0.22 ± 0.1% for Manuka and 0.8 ± 0.5% for propolis. These findings reveal a significant antibacterial effect for all the tested products. Full article
(This article belongs to the Special Issue Bacterial Pathogens Resistance and Virulence)
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Article
Studying the Gene Expression of Penicillium rubens Under the Effect of Eight Essential Oils
Antibiotics 2020, 9(6), 343; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060343 - 19 Jun 2020
Cited by 1 | Viewed by 995
Abstract
Essential oils (EOs) are well-known for their beneficial properties against a broad range of microorganisms. For the better understanding of their mechanism of action in fungi, a microarray approach was used in order to evaluate the gene expression of Penicillium chrysogenum (recently renamed [...] Read more.
Essential oils (EOs) are well-known for their beneficial properties against a broad range of microorganisms. For the better understanding of their mechanism of action in fungi, a microarray approach was used in order to evaluate the gene expression of Penicillium chrysogenum (recently renamed P. rubens) exposed to the indirect contact (vapors) of eight EOs. The selection of assayed EOs was based on their antifungal activity. The extraction of RNA and the microarray hybridization procedure were optimized for the analysis of P. rubens. Gene ontology annotation was performed to investigate the functional analysis of the genes. To uncover the metabolic pathway of these differentially expressed genes, they were mapped into the KEGG BRITE pathway database. The transcriptomic analysis showed that, from a total of 12,675 genes, only 551 genes are annotated, and the other 12,124 genes encoded hypothetical proteins. Further bioinformatic analysis demonstrated that 1350 genes were upregulated and 765 downregulated at least with half (four) of the utilizing EOs. A microarray investigation has confirmed the main impact of EOs to metabolic processes in P. rubens involved in vital functions. Presumably, this is the first time that a microarray hybridization analysis was performed in order to evaluate the gene expression of P. rubens exposed to various EOs. Full article
(This article belongs to the Special Issue Chemical Composition and Biological Activities of Essential Oils)
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Article
Antibiotic Resistance in Nosocomial Bacteria Isolated from Infected Wounds of Hospitalized Patients in Czech Republic
Antibiotics 2020, 9(6), 342; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060342 - 18 Jun 2020
Cited by 3 | Viewed by 1018
Abstract
Hospitalized patients with wounds face an increased risk of infection with multi-drug-resistant nosocomial bacteria. In this study, samples from almost 10,000 patients from big hospitals in Czech Republic with infected wounds were analyzed for the presence of bacterial pathogens. In 7693 patients (78.8%), [...] Read more.
Hospitalized patients with wounds face an increased risk of infection with multi-drug-resistant nosocomial bacteria. In this study, samples from almost 10,000 patients from big hospitals in Czech Republic with infected wounds were analyzed for the presence of bacterial pathogens. In 7693 patients (78.8%), bacterial etiological agents were identified. Members of the Enterobacterales (37.1%) and Staphyloccus aureus (21.1%) were the most prevalent pathogens. Staphyloccus aureus showed methicillin resistance in 8.6%. Almost half of the Klebsiella pneumoniae isolates were ESBL-positive and 25.6% of the Enterobacter spp. isolates were AmpC-positive. The third most prevalent Pseudomonas aeruginosa showed resistance to 19–32% of the antipseudomonal antibiotics tested. Based on the results, amoxicillin/clavulanic acid, ampicillin/sulbactam or piperacillin/tazobactam combined with gentamicin can be recommended for antibiotic treatment of infected wounds. Once the etiological agent is identified, the therapy should be adjusted according to the species and its resistance. Full article
(This article belongs to the Special Issue Antimicrobial Alternatives against Antimicrobial-Resistant Pathogens)
Article
Breast Abscesses Caused by Anaerobic Microorganisms: Clinical and Microbiological Characteristics
Antibiotics 2020, 9(6), 341; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060341 - 18 Jun 2020
Cited by 3 | Viewed by 833
Abstract
The objectives of this study were to report the antimicrobial susceptibility of 35 clinically significant anaerobic bacteria isolated from breast abscesses between March 2017 and February 2020 in a tertiary hospital in Granada (Spain) and to describe key clinical features of the patients. [...] Read more.
The objectives of this study were to report the antimicrobial susceptibility of 35 clinically significant anaerobic bacteria isolated from breast abscesses between March 2017 and February 2020 in a tertiary hospital in Granada (Spain) and to describe key clinical features of the patients. Species identification was performed mainly by MALDI-TOF MS. Antimicrobial susceptibility tests were carried out against benzylpenicillin, amoxicillin–clavulanic acid, imipenem, moxifloxacin, clindamycin, metronidazole, and piperacillin–tazobactam using the gradient diffusion technique and European Committee on Antimicrobial Susceptibility Testing EUCAST breakpoints (except for moxifloxacin). The most frequent anaerobes were Finegoldia magna (31.4%; n = 11), Actinomyces spp. (17.1%; n = 6), Propionibacterium spp. (17.1%; n = 6), and Prevotella spp. (14.2%; n = 5). Imipenem, amoxicillin–clavulanic acid, and piperacillin–tazobactam were universally active against all genera tested. High overall resistance rates to clindamycin were observed, especially for Gram-positive anaerobic cocci (56.2%) and Gram-positive anaerobic bacilli (38.4%). High resistance rates to metronidazole were also observed for Gram-positive (76.9%) and Gram-negative anaerobic bacilli (50%). High resistance rates to moxifloxacin were found for Gram-negative anaerobic bacilli (50%) and Gram-positive anaerobic cocci (31.2%). No breast abscess cases of Bacteroides spp. were detected. Routine antimicrobial susceptibility testing for anaerobes in breast abscesses may contribute to allow empirical therapies to be selected in accordance with local data on resistant strains. Full article
Review
Alkaloids from Marine Fungi: Promising Antimicrobials
Antibiotics 2020, 9(6), 340; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060340 - 18 Jun 2020
Cited by 4 | Viewed by 1552
Abstract
Resistance of pathogenic microorganisms against antimicrobials is a major threat to contemporary human society. It necessitates a perpetual influx of novel antimicrobial compounds. More specifically, Gram pathogens emerged as the most exigent danger. In our continuing quest to search for novel antimicrobial [...] Read more.
Resistance of pathogenic microorganisms against antimicrobials is a major threat to contemporary human society. It necessitates a perpetual influx of novel antimicrobial compounds. More specifically, Gram pathogens emerged as the most exigent danger. In our continuing quest to search for novel antimicrobial molecules, alkaloids from marine fungi show great promise. However, current reports of such newly discovered alkaloids are often limited to cytotoxicity studies and, moreover, neglect to discuss the enigma of their biosynthesis. Yet, the latter is often a prerequisite to make them available through sufficiently efficient processes. This review aims to summarize novel alkaloids with promising antimicrobial properties discovered in the past five years and produced by marine fungi. Several discovery strategies are summarized, and knowledge gaps in biochemical production routes are identified. Finally, links between the structure of the newly discovered molecules and their activity are proposed. Since 2015, a total of 35 new antimicrobial alkaloids from marine fungi were identified, of which 22 showed an antibacterial activity against Gram microorganisms. Eight of them can be classified as narrow-spectrum Gram antibiotics. Despite this promising ratio of novel alkaloids active against Gram microorganisms, the number of newly discovered antimicrobial alkaloids is low, due to the narrow spectrum of discovery protocols that are used and the fact that antimicrobial properties of newly discovered alkaloids are barely characterized. Alternatives are proposed in this review. In conclusion, this review summarizes novel findings on antimicrobial alkaloids from marine fungi, shows their potential as promising therapeutic candidates, and hints on how to further improve this potential. Full article
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Article
The Basis for Natural Multiresistance to Phage in Pseudomonas aeruginosa
Antibiotics 2020, 9(6), 339; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060339 - 18 Jun 2020
Cited by 5 | Viewed by 1556
Abstract
Pseudomonas aeruginosa is responsible for long-term infections and is particularly resistant to treatments when hiding inside the extracellular matrix or biofilms. Phage therapy might represent an alternative to antibiotic treatment, but up to 10% of clinical strains appear to resist multiple phages. We [...] Read more.
Pseudomonas aeruginosa is responsible for long-term infections and is particularly resistant to treatments when hiding inside the extracellular matrix or biofilms. Phage therapy might represent an alternative to antibiotic treatment, but up to 10% of clinical strains appear to resist multiple phages. We investigated the characteristics of P. aeruginosa clinical strains naturally resistant to phages and compared them to highly susceptible strains. The phage-resistant strains were defective in lipopolysaccharide (LPS) biosynthesis, were nonmotile and displayed an important degree of autolysis, releasing phages and pyocins. Complete genome sequencing of three resistant strains showed the existence of a large accessory genome made of multiple insertion elements, genomic islands, pyocins and prophages, including two phages performing lateral transduction. Mutations were found in genes responsible for the synthesis of LPS and/or type IV pilus, the major receptors for most phages. CRISPR-Cas systems appeared to be absent or inactive in phage-resistant strains, confirming that they do not play a role in the resistance to lytic phages but control the insertion of exogenous sequences. We show that, despite their apparent weakness, the multiphage-resistant strains described in this study displayed selective advantages through the possession of various functions, including weapons to eliminate other strains of the same or closely related species. Full article
(This article belongs to the Special Issue Phage Diversity for Research and Application)
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Article
Antibiotic Stewardship in Staphylococcus aureus Bloodstream Infection Treatment—Analysis Based on 29,747 Patients from One Hospital
Antibiotics 2020, 9(6), 338; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060338 - 18 Jun 2020
Cited by 1 | Viewed by 920
Abstract
Some of the most serious healthcare-associated infections (HAI) are highly deadly bloodstream infections (BSIs) caused by Staphylococcus aureus. The aim of the study was to analyse compliance of treatment practice with clinical guidelines in patients with S. aureus BSIs. The study was [...] Read more.
Some of the most serious healthcare-associated infections (HAI) are highly deadly bloodstream infections (BSIs) caused by Staphylococcus aureus. The aim of the study was to analyse compliance of treatment practice with clinical guidelines in patients with S. aureus BSIs. The study was conducted at the Sosnowiec Hospital, Poland in 2019. During the study, 29,747 patients were hospitalized and 41 S. aureus BSIs (only HAIs) episodes were observed. According to local clinical practice guidelines, each case of BSI required blood cultures, echocardiography and control culture after the implementation of the targeted therapy. Incidence rate of S. aureus BSI was 0.8/1000 admissions; the greatest department admission rates were in the ICU (19.3/1000 admissions) and in the Nephrology Department (8.7/1000 admissions). Only 2 patients were treated following the protocol (4.8%); the most common errors were the use of an inappropriate drug or incorrect duration of antibiotic treatment. No patient underwent echocardiography, and control cultures were performed in 70% of cases. The case fatality rate was 7.3%. A satisfactorily low case fatality rate was found despite the poor antibiotic stewardship. Lack of discipline concerning antibiotic use can strongly impact the observed high drug resistance in HAIs and high Clostridioides difficile incidence rate in the studied hospital. Full article
(This article belongs to the Special Issue Surveillance of Antimicrobial Use on Different Levels)
Review
Metal–Peptide Complexes as Promising Antibiotics to Fight Emerging Drug Resistance: New Perspectives in Tuberculosis
Antibiotics 2020, 9(6), 337; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060337 - 18 Jun 2020
Cited by 5 | Viewed by 1130
Abstract
In metal-peptide interactions, cations form stable complexes through bonds with coordinating groups as side chains of amino acids. These compounds, among other things, exert a wide variety of antimicrobial activities through structural changes of peptides upon metal binding and redox chemistry. They exhibit [...] Read more.
In metal-peptide interactions, cations form stable complexes through bonds with coordinating groups as side chains of amino acids. These compounds, among other things, exert a wide variety of antimicrobial activities through structural changes of peptides upon metal binding and redox chemistry. They exhibit different mechanisms of action (MOA), including the modification of DNA/RNA, protein and cell wall synthesis, permeabilization and modulation of gradients of cellular membranes. Nowadays, the large increase in antibiotic resistance represents a crucial problem to limit progression at the pandemic level of the diseases that seemed nearly eradicated, such as tuberculosis (Tb). Mycobacterium tuberculosis (Mtb) is intrinsically resistant to many antibiotics due to chromosomal mutations which can lead to the onset of novel strains. Consequently, the maximum pharmaceutical effort should be focused on the development of new therapeutic agents and antimicrobial peptides can represent a valuable option as a copious source of potential bioactive compounds. The introduction of a metal center can improve chemical diversity and hence specificity and bioavailability while, in turn, the coordination to peptides of metal complexes can protect them and enhance their poor water solubility and air stability: the optimization of these parameters is strictly required for drug prioritization and to obtain potent inhibitors of Mtb infections with novel MOAs. Here, we present a panoramic review of the most recent findings in the field of metal complex-peptide conjugates and their delivery systems with the potential pharmaceutical application as novel antibiotics in Mtb infections. Full article
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Review
Stilbenoids: A Natural Arsenal against Bacterial Pathogens
Antibiotics 2020, 9(6), 336; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060336 - 18 Jun 2020
Cited by 7 | Viewed by 1189
Abstract
The escalating emergence of resistant bacterial strains is one of the most important threats to human health. With the increasing incidence of multi-drugs infections, there is an urgent need to restock our antibiotic arsenal. Natural products are an invaluable source of inspiration in [...] Read more.
The escalating emergence of resistant bacterial strains is one of the most important threats to human health. With the increasing incidence of multi-drugs infections, there is an urgent need to restock our antibiotic arsenal. Natural products are an invaluable source of inspiration in drug design and development. One of the most widely distributed groups of natural products in the plant kingdom is represented by stilbenoids. Stilbenoids are synthesised by plants as means of protection against pathogens, whereby the potential antimicrobial activity of this class of natural compounds has attracted great interest in the last years. The purpose of this review is to provide an overview of recent achievements in the study of stilbenoids as antimicrobial agents, with particular emphasis on the sources, chemical structures, and the mechanism of action of the most promising natural compounds. Attention has been paid to the main structure modifications on the stilbenoid core that have expanded the antimicrobial activity with respect to the parent natural compounds, opening the possibility of their further development. The collected results highlight the therapeutic versatility of natural and synthetic resveratrol derivatives and provide a prospective insight into their potential development as antimicrobial agents. Full article
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Article
Using GFP-Tagged Escherichia coli to Investigate the Persistence of Fecal Bacteria in Vegetated Wetlands: An Experimental Approach
Antibiotics 2020, 9(6), 335; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060335 - 18 Jun 2020
Viewed by 872
Abstract
The contamination of surface water by pathogenic bacteria of human origin is an important public health issue. Wetlands can be contaminated with fecal bacteria by water originating from different sources, such as wastewater treatment plants and agriculture. Escherichia coli is a commensal of [...] Read more.
The contamination of surface water by pathogenic bacteria of human origin is an important public health issue. Wetlands can be contaminated with fecal bacteria by water originating from different sources, such as wastewater treatment plants and agriculture. Escherichia coli is a commensal of the human gut flora and the major indication of fecal contamination in surface water. Little is known about the association between fecal bacteria and submerged macrophytes and how this may influence the water quality. We questioned whether macrophytes enhance or inhibit the bacterial growth in wetlands. For this purpose, we grew four different species of macrophytes (Mentha aquatica, Baldellia ranunculoides, Sparganium emersum and Elodea canadensis, in mono- or multispecies cultures) in aquatic rhizotrons and inoculated the devices with a fluorescent strain of Escherichia coli (producing a green fluorescent protein) to simulate the fecal contamination of wetlands. Bacterial survival was monitored by measuring the fluorescence for 19 days. We found (i) that contaminated sediments did not release E. coli in the water column in lentic conditions and (ii) that monocultures of E. canadensis, M. aquatica and S. emersum reduced the E. coli concentration in the water column. This suggests that aquatic plant species may be used in constructed wetlands to clear surface freshwater from bacteria of fecal origin. Full article
(This article belongs to the Special Issue Antibacterial Activity of Plant Extracts and Essential Oils)
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Article
Phytochemical Compositions and Biological Activities of Essential Oils from the Leaves, Rhizomes and Whole Plant of Hornstedtia bella Škorničk
Antibiotics 2020, 9(6), 334; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060334 - 18 Jun 2020
Cited by 28 | Viewed by 1114
Abstract
The rapid emergence of drug-resistant strains and novel viruses have motivated the search for new anti-infectious agents. In this study, the chemical compositions and cytotoxicity, as well as the antibacterial, antifungal, antitrichomonas, and antiviral activities of essential oils from the leaves, rhizomes, and [...] Read more.
The rapid emergence of drug-resistant strains and novel viruses have motivated the search for new anti-infectious agents. In this study, the chemical compositions and cytotoxicity, as well as the antibacterial, antifungal, antitrichomonas, and antiviral activities of essential oils from the leaves, rhizomes, and whole plant of Hornstedtia bella were investigated. The GC/MS analysis showed that β-pinene, E-β-caryophyllene, and α-humulene were found at high concentrations in the essential oils. The essential oils exhibited (i) inhibition against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis with minimum inhibitory concentrations (MIC) and minimum lethal concentration (MLC) values from 1 to 4% (v/v); (ii) MIC and MLC values from 2 to 16% (v/v) in Candida tropicalis and Candida parapsilosis; (iii) MIC and MLC values from 4 to 16% in Enterococcus faecalis; and (iv) MIC and MLC values from 8 to greater than or equal to 16% (v/v) in the remaining strains, including Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Candida albicans, and Candida glabrata. In antitrichomonas activity, the leaves and whole-plant oils of Hornstedtia bella possessed IC50, IC90, and MLC values of 0.008%, 0.016%, and 0.03% (v/v), respectively, whilst those of rhizomes oil had in turn, 0.004%, 0.008%, and 0.016% (v/v).Besides, the leaf oil showed a weak cytotoxicity against Vero 76 and MRC-5; meanwhile, rhizomes and whole-plant oils did not exert any toxic effects on cell monolayers. Finally, these oils were not active against EV-A71. Full article
Article
In Vitro Toxicity, Antioxidant, Anti-Inflammatory, and Antidiabetic Potential of Sphaerostephanos unitus (L.) Holttum
Antibiotics 2020, 9(6), 333; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9060333 - 18 Jun 2020
Cited by 3 | Viewed by 926
Abstract
Pteridophytes have been widely used in several systems of medicine. Several reports have increasingly assessed their bioactive effects, but for Sphaerostephanos unitus (L.) Holttum, only its antibacterial potential has been assessed. In this sense, the present study was carried out to reveal the [...] Read more.
Pteridophytes have been widely used in several systems of medicine. Several reports have increasingly assessed their bioactive effects, but for Sphaerostephanos unitus (L.) Holttum, only its antibacterial potential has been assessed. In this sense, the present study was carried out to reveal the phytochemical profile and to determine the toxicity, antioxidant, antidiabetic, and anti-inflammatory potential of S. unitus. Brine shrimp lethality, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, phosphomolybdenum assay, superoxide radical scavenging activity, 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) assay (ABTS), and in vitro α-amylase inhibitory and membrane stabilization assays were applied. S. unitus extract toxicity showed variable mortality percentages, with LC50 values ranging from 4 to 30 mg/mL. DPPH radical scavenging effects of S. unitus extracts were as follows: methanol > acetone > petroleum ether > chloroform. S. unitus acetone extract displayed the strongest phosphomolybdenum reduction (10 ± 2 mg Ascorbic Acid Equivalent/g). The studied extracts also revealed efficient, superoxide scavenging effects in a dose-dependent manner. In S. unitus, the highest ABTS radical scavenging rate was observed in the chloroform extract (3000 ± 40 µmol/g). The S. unitus anti-inflammatory effect was as follows: petroleum ether > chloroform > methanol > acetone. In S. unitus extract, the highest percentage of α-amylase activity (80%) was observed for the petroleum ether extract (25 µg/mL). Faced with these findings, further studies should be performed to isolate and identify the S. unitus compounds responsible for their antioxidant, antidiabetic and anti-inflammatory effects. Full article
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