Antibacterial Resistance and Novel Strategies to Eradicate Bacterial Biofilms

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Mechanism and Evolution of Antibiotic Resistance".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 22915

Special Issue Editor


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Guest Editor
Infection Immunity and Inflammation theme, Sydney Institute for Infectious Diseases, Charles Perkins Centre, School of Medical Sciences, The University of Sydney, Sydney, NSW, Australia
Interests: bacterial biofilm; quorum sensing in bacteria; antimicrobial drug development; host-pathogen interactions
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Bacterial resistance to existing and commonly used antibiotics, disinfectants, and detergents have raised a global alarm in regards to public health and economy. Bacteria which prefer to exist in biofilm state have greater resistance to antibacterial agents in comparison to those in planktonic state. Understanding the exact mechanisms by which bacteria develop resistance to antibacterial agents and the development of novel and innovative strategies to eradicate bacteria/biofilms and their associated infections are of the highest priority.

The Special Issue will primarily focus on antibacterial resistance mechanisms in bacteria and the development of new antibacterial agents targeting biofilm disruption. This Issue will consist of manuscripts, including original research articles, review articles, case series, and opinion papers. Specifically, work from the following fields of research will be included in this Issue:

Antibiotic resistance mechanisms in bacteria;

Antibiotic stewardship—use and misuse;

Bacterial virulence factors and their role in pathogenicity and infection;

Bacterial extracellular substances and their role in biofilm formation;

Host immunological response against bacteria;

Novel molecules targeting quorum-sensing inhibition in bacteria;

New antibacterial agents and their mode of action against bacterial biofilms;

Antibacterial coatings for biomedical applications;

Enzymatic degradation of bacterial biofilms;

Biofilm removal from the environment (e.g., water sources);

Food pathogens and control strategies.

Dr. Theerthankar Das
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (7 papers)

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Editorial

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3 pages, 174 KiB  
Editorial
Editorial for Special Issue “Antibacterial Resistance and Novel Strategies to Eradicate Bacterial Biofilms”
by Theerthankar Das
Antibiotics 2022, 11(9), 1184; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11091184 - 01 Sep 2022
Cited by 1 | Viewed by 1638
Abstract
Bacterial resistance to antimicrobial agents, including antibiotics, disinfectants, and detergents, is on the rise, with consequences associated with morbidity, mortality, and economic loss in the healthcare sector [...] Full article

Research

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17 pages, 1335 KiB  
Article
A Ternary Copper (II) Complex with 4-Fluorophenoxyacetic Acid Hydrazide in Combination with Antibiotics Exhibits Positive Synergistic Effect against Salmonella Typhimurium
by Guilherme Paz Monteiro, Roberta Torres de Melo, Micaela Guidotti-Takeuchi, Carolyne Ferreira Dumont, Rosanne Aparecida Capanema Ribeiro, Wendell Guerra, Luana Munique Sousa Ramos, Drielly Aparecida Paixão, Fernanda Aparecida Longato dos Santos, Dália dos Prazeres Rodrigues, Peter Boleij, Patrícia Giovana Hoepers and Daise Aparecida Rossi
Antibiotics 2022, 11(3), 388; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11030388 - 15 Mar 2022
Cited by 3 | Viewed by 2559
Abstract
Salmonella spp. continues to figure prominently in world epidemiological registries as one of the leading causes of bacterial foodborne disease. We characterised 43 Brazilian lineages of Salmonella Typhimurium (ST) strains, characterized drug resistance patterns, tested copper (II) complex as control options, and proposed [...] Read more.
Salmonella spp. continues to figure prominently in world epidemiological registries as one of the leading causes of bacterial foodborne disease. We characterised 43 Brazilian lineages of Salmonella Typhimurium (ST) strains, characterized drug resistance patterns, tested copper (II) complex as control options, and proposed effective antimicrobial measures. The minimum inhibitory concentration was evaluated for seven antimicrobials, isolated and combined with the copper (II) complex [Cu(4-FH)(phen)(ClO4)2] (4-FH = 4-fluorophenoxyacetic acid hydrazide and phen = 1,10-phenanthroline), known as DRI-12, in planktonic and sessile ST. In parallel, 42 resistance genes were screened (PCR/microarray). All strains were multidrug resistant (MDR). Resistance to carbapenems and polymyxins (86 and 88%, respectively) have drawn attention to the emergence of the problem in Brazil, and resistance is observed also to CIP and CFT (42 and 67%, respectively), the drugs of choice in treatment. Resistance to beta-lactams was associated with the genes blaTEM/blaCTX-M in 39% of the strains. Lower concentrations of DRI-12 (62.7 mg/L, or 100 μM) controlled planktonic and sessile ST in relation to AMP/SUL/TET and AMP/SUL/TET/COL, respectively. The synergistic effect provided by DRI-12 was significant for COL/CFT and COL/AMP in planktonic and sessile ST, respectively, and represents promising alternatives for the control of MDR ST. Full article
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18 pages, 3512 KiB  
Article
Transcriptome Analysis of the Response of Mature Helicobacter pylori Biofilm to Different Doses of Lactobacillus salivarius LN12 with Amoxicillin and Clarithromycin
by Fang Jin and Hong Yang
Antibiotics 2022, 11(2), 262; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11020262 - 17 Feb 2022
Cited by 5 | Viewed by 2105
Abstract
Helicobacter pylori is a gastrointestinal pathogen with a high infection rate. Probiotics are clinically used as an adjuvant to improve the cure rate and reduce the side effects of antibiotic treatment for H. pylori. This study is the first to explore the [...] Read more.
Helicobacter pylori is a gastrointestinal pathogen with a high infection rate. Probiotics are clinically used as an adjuvant to improve the cure rate and reduce the side effects of antibiotic treatment for H. pylori. This study is the first to explore the effects of a cell-free supernatant of high- or low-dose Lactobacillus salivarius LN12 combined with amoxicillin (AMX) and clarithromycin (CLR) on H. pylori 3192 biofilms in terms of the biofilm biomass, survival rates, biofilm structure, and transcriptome. The results showed that the combination of the CFS of high-dose LN12 with AMX and CLR had stronger effects on the biofilm biomass, survival rate, and structure of H. pylori 3192 biofilms. H. pylori 3192 biofilms may increase the expression of NADH-related genes and downregulate flagellar assembly and quorum sensing-related receptor genes to deal with the stronger stress effects of high-dose LN12 with AMX and CLR. In conclusion, the biofilm biomass, survival rate, structure, and transcriptome results showed that the combination of LN12 CFS with AMX and CLR had dose effects. We recommend that compared with low doses, high doses of L. salivarus LN12 combined with AMX and CLR may be more effective for H. pylori biofilm than low doses. Full article
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17 pages, 4076 KiB  
Article
N-Acetylcysteine Protects Bladder Epithelial Cells from Bacterial Invasion and Displays Antibiofilm Activity against Urinary Tract Bacterial Pathogens
by Arthika Manoharan, Samantha Ognenovska, Denis Paino, Greg Whiteley, Trevor Glasbey, Frederik H. Kriel, Jessica Farrell, Kate H. Moore, Jim Manos and Theerthankar Das
Antibiotics 2021, 10(8), 900; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10080900 - 23 Jul 2021
Cited by 13 | Viewed by 5235
Abstract
Introduction: Urinary tract infections (UTIs) affect more than 150 million individuals annually. A strong correlation exists between bladder epithelia invasion by uropathogenic bacteria and patients with recurrent UTIs. Intracellular bacteria often recolonise epithelial cells post-antibiotic treatment. We investigated whether N-acetylcysteine (NAC) could prevent [...] Read more.
Introduction: Urinary tract infections (UTIs) affect more than 150 million individuals annually. A strong correlation exists between bladder epithelia invasion by uropathogenic bacteria and patients with recurrent UTIs. Intracellular bacteria often recolonise epithelial cells post-antibiotic treatment. We investigated whether N-acetylcysteine (NAC) could prevent uropathogenic E. coli and E. faecalis bladder cell invasion, in addition to its effect on uropathogens when used alone or in combination with ciprofloxacin. Methods: An invasion assay was performed in which bacteria were added to bladder epithelial cells (BECs) in presence of NAC and invasion was allowed to occur. Cells were washed with gentamicin, lysed, and plated for enumeration of the intracellular bacterial load. Cytotoxicity was evaluated by exposing BECs to various concentrations of NAC and quantifying the metabolic activity using resazurin at different exposure times. The effect of NAC on the preformed biofilms was also investigated by treating 48 h biofilms for 24 h and enumerating colony counts. Bacteria were stained with propidium iodide (PI) to measure membrane damage. Results: NAC completely inhibited BEC invasion by multiple E. coli and E. faecalis clinical strains in a dose-dependent manner (p < 0.01). This was also evident when bacterial invasion was visualised using GFP-tagged E. coli. NAC displayed no cytotoxicity against BECs despite its intrinsic acidity (pH ~2.6), with >90% cellular viability 48 h post-exposure. NAC also prevented biofilm formation by E. coli and E. faecalis and significantly reduced bacterial loads in 48 h biofilms when combined with ciprofloxacin. NAC visibly damaged E. coli and E. faecalis bacterial membranes, with a threefold increase in propidium iodide-stained cells following treatment (p < 0.05). Conclusions: NAC is a non-toxic, antibiofilm agent in vitro and can prevent cell invasion and IBC formation by uropathogens, thus providing a potentially novel and efficacious treatment for UTIs. When combined with an antibiotic, it may disrupt bacterial biofilms and eliminate residual bacteria. Full article
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15 pages, 1142 KiB  
Article
Novel Nitro-Heteroaromatic Antimicrobial Agents for the Control and Eradication of Biofilm-Forming Bacteria
by Heidi N. Koenig, Gregory M. Durling, Danica J. Walsh, Tom Livinghouse and Philip S. Stewart
Antibiotics 2021, 10(7), 855; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10070855 - 14 Jul 2021
Cited by 4 | Viewed by 2563
Abstract
The synthesis and biological activity of several novel nitrothiazole, nitrobenzothiazole, and nitrofuran containing antimicrobial agents for the eradication of biofilm-forming Gram-negative and Gram-positive pathogens is described. Nitazoxanide (NTZ), nitrofurantoin, and furazolidone are commercial antimicrobials which were used as models to show how structural [...] Read more.
The synthesis and biological activity of several novel nitrothiazole, nitrobenzothiazole, and nitrofuran containing antimicrobial agents for the eradication of biofilm-forming Gram-negative and Gram-positive pathogens is described. Nitazoxanide (NTZ), nitrofurantoin, and furazolidone are commercial antimicrobials which were used as models to show how structural modification improved activity toward planktonic bacteria via minimum inhibitory concentration (MIC) assays and biofilms via minimum biofilm eradication concentration (MBEC) assays. Structure–activity relationship (SAR) studies illustrate the ways in which improvements have been made to the aforementioned antimicrobial agents. It is of particular interest in this regard that the introduction of a chloro substituent at the 5-position of NTZ (analog 1b) resulted in marked activity enhancement, as did the replacement of the 2-acetoxy substituent in the latter compound with a basic amine group (analog 7b). It is also of importance that analog 4a, which is a simple methacrylamide, displayed noteworthy activity against S. epidermidis biofilms. These lead compounds identified to have high activity towards biofilms provide promise as starting points in future pro-drug studies. Full article
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Review

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20 pages, 1696 KiB  
Review
Classic vs. Novel Antibacterial Approaches for Eradicating Dental Biofilm as Adjunct to Periodontal Debridement: An Evidence-Based Overview
by Ali Abdulkareem, Hayder Abdulbaqi, Sarhang Gul, Mike Milward, Nibras Chasib and Raghad Alhashimi
Antibiotics 2022, 11(1), 9; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11010009 - 22 Dec 2021
Cited by 9 | Viewed by 4332
Abstract
Periodontitis is a multifactorial chronic inflammatory disease that affects tooth-supporting soft/hard tissues of the dentition. The dental plaque biofilm is considered as a primary etiological factor in susceptible patients; however, other factors contribute to progression, such as diabetes and smoking. Current management utilizes [...] Read more.
Periodontitis is a multifactorial chronic inflammatory disease that affects tooth-supporting soft/hard tissues of the dentition. The dental plaque biofilm is considered as a primary etiological factor in susceptible patients; however, other factors contribute to progression, such as diabetes and smoking. Current management utilizes mechanical biofilm removal as the gold standard of treatment. Antibacterial agents might be indicated in certain conditions as an adjunct to this mechanical approach. However, in view of the growing concern about bacterial resistance, alternative approaches have been investigated. Currently, a range of antimicrobial agents and protocols have been used in clinical management, but these remain largely non-validated. This review aimed to evaluate the efficacy of adjunctive antibiotic use in periodontal management and to compare them to recently suggested alternatives. Evidence from in vitro, observational and clinical trial studies suggests efficacy in the use of adjunctive antimicrobials in patients with grade C periodontitis of young age or where the associated risk factors are inconsistent with the amount of bone loss present. Meanwhile, alternative approaches such as photodynamic therapy, bacteriophage therapy and probiotics showed limited supportive evidence, and more studies are warranted to validate their efficiency. Full article
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18 pages, 1758 KiB  
Review
Anti-Biofilm Molecules Targeting Functional Amyloids
by Leticia Matilla-Cuenca, Alejandro Toledo-Arana and Jaione Valle
Antibiotics 2021, 10(7), 795; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10070795 - 29 Jun 2021
Cited by 13 | Viewed by 3364
Abstract
The choice of an effective therapeutic strategy in the treatment of biofilm-related infections is a significant issue. Amyloids, which have been historically related to human diseases, are now considered to be prevailing structural components of the biofilm matrix in a wide range of [...] Read more.
The choice of an effective therapeutic strategy in the treatment of biofilm-related infections is a significant issue. Amyloids, which have been historically related to human diseases, are now considered to be prevailing structural components of the biofilm matrix in a wide range of bacteria. This assumption creates the potential for an exciting research area, in which functional amyloids are considered to be attractive targets for drug development to dissemble biofilm structures. The present review describes the best-characterized bacterial functional amyloids and focuses on anti-biofilm agents that target intrinsic and facultative amyloids. This study provides a better understanding of the different modes of actions of the anti-amyloid molecules to inhibit biofilm formation. This information can be further exploited to improve the therapeutic strategies to combat biofilm-related infections. Full article
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