Special Issue "Systems Involved in Antimicrobial Resistance and Virulence of Clinically Important Pathogens"

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: closed (31 January 2021).

Special Issue Editors

Dr. Costas C. Papagiannitsis
E-Mail Website
Guest Editor
Department of Microbiology, Faculty of Medicine, University of Thessaly, Larissa, Greece
Interests: antimicrobial resistance; resistance mechanisms; carbapenemase; mobile genetic elements (MGEs); whole-genome sequencing (WGS)
Special Issues, Collections and Topics in MDPI journals
Dr. Ibrahim Bitar
E-Mail Website
Guest Editor
Department of Microbiology, Faculty of Medicine, University Hospital in Pilsen, Charles University, 32300 Pilsen, Czech Republic
Interests: whole genome sequencing (WGS); mobile elements; plasmids; antimicrobial resistance; Enterobacterales; Candida albicans; Acinetobacter baumannii; Streptococcus pneumoniae; virulence

Special Issue Information

Dear Colleagues,

The spread of multidrug resistant (MDR) microbes has caused a public health crisis of global dimensions. MDR bacteria, and more specifically the carbapenemase-producing Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii, have already been detected all over the globe. Genes encoding carbapenemases are usually associated with mobile genetic elements (MGEs) such as integrons, insertion sequences, transposons, and plasmids. Plasmids play an important role in the epidemiology of antibiotic resistance, since acquisition of various resistance genes on a replicon can result in resistance to multiple antibiotics of the host bacterial cell. Additionally, plasmids harbor various genes encoding virulence or adhesion factors, which offer an advantage to the bacterium for successful invasion and survival within the infected host.

Furthermore, bacteria like A. baumannii and P. aeruginosa show a great propensity to form biofilms on medical devices. It is widely accepted that pathogens within biofilm communities have increased tolerance to extracellular stress. Biofilms have become important virulence factors for A. baumannii, as they provide an insulation that allows bacteria to survive under harsh environmental conditions. Eventually, this makes the organisms tolerant to multiple antimicrobials, giving them multidrug resistance. Additionally, P. aeruginosa is known to produce a variety of cell-associated factors and secreted toxins such as exoenzymes, toxins, and secondary metabolites. These factors help the bacterium to facilitate successful infection and colonization across a wide range of environments. The synthesis of these factors is regulated by a cell-to-cell signaling mechanism referred to as quorum-sensing. Quorum sensing signifies the mode of communication among bacteria to maintain the population density via signal molecules called ‘auto-inducers’. Such cell-to-cell communication has been associated with processes such as bioluminescence, swarming, twitching, antibiotic production, conjugative DNA transfer, sporulation, production of virulence markers, biofilm formation, and biosurfactant production.

Finally, many clones of bacterial strains process a CRISPR/Cas system, which is an adaptive immune system that allows bacteria to limit the entry of genetic elements such as bacteriophages and plasmids. Interestingly, several recent studies have pointed at direct links of CRISPR/Cas systems to regulation of stress-related phenomena. Thus, exploring the role of those systems in bacterial infections is important for fighting MDR pathogens.

The scope of this Special Issue is to collect original contributions on the systems involved in antimicrobial resistance and virulence of clinically important pathogens. It is our pleasure to invite you to submit research articles, short communications, or review articles related to these topics.

Dr. Costas C. Papagiannitsis
Dr. Ibrahim Bitar
Guest Editors

Manuscript Submission Information

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Keywords

  • Antimicrobial resistance
  • Mobile elements
  • Plasmids
  • Biofilm formation
  • Virulence
  • Enterobacterales
  • Yeast
  • Acinetobacter baumannii
  • Pseudomonas aeruginosa
  • Quorum-sensing
  • CRISPR/Cas system

Published Papers (12 papers)

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Research

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Article
Extensive Comparative Genomic Analysis of Enterococcus faecalis and Enterococcus faecium Reveals a Direct Association between the Absence of CRISPR–Cas Systems, the Presence of Anti-Endonuclease (ardA) and the Acquisition of Vancomycin Resistance in E. faecium
Microorganisms 2021, 9(6), 1118; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9061118 - 21 May 2021
Viewed by 902
Abstract
Here, we performed a comparative genomic analysis of all available genomes of E. faecalis (n = 1591) and E. faecium (n = 1981) and investigated the association between the presence or absence of CRISPR-Cas systems, endonuclease/anti-endonuclease systems and the acquisition of [...] Read more.
Here, we performed a comparative genomic analysis of all available genomes of E. faecalis (n = 1591) and E. faecium (n = 1981) and investigated the association between the presence or absence of CRISPR-Cas systems, endonuclease/anti-endonuclease systems and the acquisition of antimicrobial resistance, especially vancomycin resistance genes. Most of the analysed Enterococci were isolated from humans and less than 14% of them were from foods and animals. We analysed and detected CRISPR–Cas systems in 75.36% of E. faecalis genomes and only 4.89% of E. faecium genomes with a significant difference (p-value < 10−5). We found a negative correlation between the number of CRISPR–Cas systems and genome size (r = −0.397, p-value < 10−5) and a positive correlation between the genome %GC content and the number of CRISPR–Cas systems (r = 0.215, p-value < 10−5). Our findings showed that the presence of the anti-endonuclease ardA gene may explain the decrease in the number of CRISPR–Cas systems in E. faecium, known to deactivate the endonucleases’ protective activities and enable the E. faecium genome to be versatile in acquiring mobile genetic elements, including carriers of antimicrobial resistance genes, especially vanB. Most importantly, we observed that there was a direct association between the absence of CRISPR–Cas, the presence of the anti-CRISPR ardA gene and the acquisition of vancomycin resistance genes. Full article
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Article
Genomic and Phenotypic Analysis of Linezolid-Resistant Staphylococcus epidermidis in a Tertiary Hospital in Innsbruck, Austria
Microorganisms 2021, 9(5), 1023; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9051023 - 10 May 2021
Cited by 1 | Viewed by 800
Abstract
Whole genome sequencing is a useful tool to monitor the spread of resistance mechanisms in bacteria. In this retrospective study, we investigated genetic resistance mechanisms, sequence types (ST) and respective phenotypes of linezolid-resistant Staphylococcus epidermidis (LRSE, n = 129) recovered from a cohort [...] Read more.
Whole genome sequencing is a useful tool to monitor the spread of resistance mechanisms in bacteria. In this retrospective study, we investigated genetic resistance mechanisms, sequence types (ST) and respective phenotypes of linezolid-resistant Staphylococcus epidermidis (LRSE, n = 129) recovered from a cohort of patients receiving or not receiving linezolid within a tertiary hospital in Innsbruck, Austria. Hereby, the point mutation G2603U in the 23S rRNA (n = 91) was the major resistance mechanism followed by the presence of plasmid-derived cfr (n = 30). The majority of LRSE isolates were ST2 strains, followed by ST5. LRSE isolates expressed a high resistance level to linezolid with a minimal inhibitory concentration of ≥256 mg/L (n = 83) in most isolates, particularly in strains carrying the cfr gene (p < 0.001). Linezolid usage was the most prominent (but not the only) trigger for the development of linezolid resistance. However, administration of linezolid was not associated with a specific resistance mechanism. Restriction of linezolid usage and the monitoring of plasmid-derived cfr in LRSE are potential key steps to reduce linezolid resistance and its transmission to more pathogenic Gram-positive bacteria. Full article
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Article
Elevated Incidences of Antimicrobial Resistance and Multidrug Resistance in the Maumee River (Ohio, USA), a Major Tributary of Lake Erie
Microorganisms 2021, 9(5), 911; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9050911 - 24 Apr 2021
Viewed by 658
Abstract
Maumee River, the major tributary in the western basin of Lake Erie, serves as one of major sources of freshwater in the area, supplying potable, recreational, and industrial water. In this study we collected water samples from four sites in the Maumee River [...] Read more.
Maumee River, the major tributary in the western basin of Lake Erie, serves as one of major sources of freshwater in the area, supplying potable, recreational, and industrial water. In this study we collected water samples from four sites in the Maumee River Bay between 2016–2017 and E. coli was isolated, enumerated, and analyzed for antimicrobial resistance (AMR) and multidrug resistance (MDR). Strikingly, 95% of the total isolates were found to be resistant to at least one antibiotic. A very high resistance to the drugs cephalothin (95.3%), ampicillin (38.3%), tetracycline (8.8%), gentamicin (8.2%), ciprofloxacin (4.2%), cefoperazone (4%), and sulfamethoxazole (1.5%) was observed within isolates from all four sampling sites. Percentages of AMR and MDR was consistently very high in the summer and fall months, whereas it was observed to be lowest in the winter. A remarkably high number of the isolates were detected to be MDR—95% resistant to ≥1 antibiotic, 43% resistant to ≥2 antibiotics, 15% resistant to ≥3 antibiotics, 4.9% resistant to ≥4 antibiotic and 1.2% resistant to ≥5 antibiotics. This data will serve in better understanding the environmental occurrence and dissemination of AMR/MDR in the area and assist in improving and establishing control measures. Full article
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Article
Multi-Drug Resistant Plasmids with ESBL/AmpC and mcr-5.1 in Paraguayan Poultry Farms: The Linkage of Antibiotic Resistance and Hatcheries
Microorganisms 2021, 9(4), 866; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9040866 - 17 Apr 2021
Cited by 1 | Viewed by 771
Abstract
Poultry represents a common source of bacteria with resistance to antibiotics including the critically important ones. Selective cultivation using colistin, cefotaxime and meropenem was performed for 66 chicken samples coming from 12 farms in Paraguay while two breeding companies supplied the farms. A [...] Read more.
Poultry represents a common source of bacteria with resistance to antibiotics including the critically important ones. Selective cultivation using colistin, cefotaxime and meropenem was performed for 66 chicken samples coming from 12 farms in Paraguay while two breeding companies supplied the farms. A total of 62 Escherichia coli and 22 Klebsiella pneumoniae isolates were obtained and representative isolates were subjected to whole-genome sequencing. Relatively high prevalence of phylogenetic group D and F was observed in E. coli isolates and several zoonotic sequence types (STs) including ST457 (14 isolates), ST38 (5), ST10 (2), ST117 (2) or ST93 (4) were detected. Isolates from three farms, which purchased chicken from a Paraguayan hatchery showed higher prevalence of mcr-5.1 and blaCTX-M-8 compared to the other nine farms, which purchased chickens from a Brazilian hatchery. Moreover, none of the K. pneumoniae isolates were linked to the Paraguayan hatchery. ESBL/AmpC and mcr-5-carrying multi-drug resistant (MDR) plasmids were characterized, and complete sequences were obtained for eight plasmids. The study shed light on Paraguayan poultry farms as a reservoir of antibiotic resistance commonly conferred via MDR plasmids and showed linkage between resistance and origin of the chickens at the hatcheries level. Full article
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Communication
Culture-Independent Genotyping, Virulence and Antimicrobial Resistance Gene Identification of Staphylococcus aureus from Orthopaedic Implant-Associated Infections
Microorganisms 2021, 9(4), 707; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9040707 - 30 Mar 2021
Cited by 1 | Viewed by 845
Abstract
Our culture-independent nanopore shotgun metagenomic sequencing protocol on biopsies has the potential for same-day diagnostics of orthopaedic implant-associated infections (OIAI). As OIAI are frequently caused by Staphylococcus aureus, we included S. aureus genotyping and virulence gene detection to exploit the protocol to [...] Read more.
Our culture-independent nanopore shotgun metagenomic sequencing protocol on biopsies has the potential for same-day diagnostics of orthopaedic implant-associated infections (OIAI). As OIAI are frequently caused by Staphylococcus aureus, we included S. aureus genotyping and virulence gene detection to exploit the protocol to its fullest. The aim was to evaluate S. aureus genotyping, virulence and antimicrobial resistance genes detection using the shotgun metagenomic sequencing protocol. This proof of concept study included six patients with S. aureus-associated OIAI at Akershus University Hospital, Norway. Five tissue biopsies from each patient were divided in two: (1) conventional microbiological diagnostics and genotyping, and whole genome sequencing (WGS) of S. aureus isolates; (2) shotgun metagenomic sequencing of DNA from the biopsies. Consensus sequences were analysed using spaTyper, MLST, VirulenceFinder, and ResFinder from the Center for Genomic Epidemiology (CGE). MLST was also compared using krocus. All spa-types, one CGE and four krocus MLST results matched Sanger sequencing results. Virulence gene detection matched between WGS and shotgun metagenomic sequencing. ResFinder results corresponded to resistance phenotype. S. aureus spa-typing, and identification of virulence and antimicrobial resistance genes are possible using our shotgun metagenomics protocol. MLST requires further optimization. The protocol has potential application to other species and infection types. Full article
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Article
An Update on Wastewater Multi-Resistant Bacteria: Identification of Clinical Pathogens Such as Escherichia coli O25b:H4-B2-ST131-Producing CTX-M-15 ESBL and KPC-3 Carbapenemase-Producing Klebsiella oxytoca
Microorganisms 2021, 9(3), 576; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9030576 - 11 Mar 2021
Cited by 2 | Viewed by 821
Abstract
Wastewater treatment plants (WWTPs) are significant reservoirs of bacterial resistance. This work aims to identify the determinants of resistance produced by Gram-negative bacteria in the influent and effluent of two WWTPs in Portugal. A total of 96 wastewater samples were obtained between 2016 [...] Read more.
Wastewater treatment plants (WWTPs) are significant reservoirs of bacterial resistance. This work aims to identify the determinants of resistance produced by Gram-negative bacteria in the influent and effluent of two WWTPs in Portugal. A total of 96 wastewater samples were obtained between 2016 and 2019. The numbers of total aerobic and fecal contamination bacteria were evaluated, and genomic features were searched by polymerase chain reaction (PCR) and Next-Generation Sequencing (NGS). Enterobacteriaceae corresponded to 78.6% (n = 161) of the 205 isolates identified by 16sRNA. The most frequent isolates were Escherichia spp. (57.1%, n = 117), followed by Aeromonas spp. (16.1%, n = 33) and Klebsiella spp. (12.7%, n = 26). The remaining 29 isolates (14.1%) were distributed across 10 different genera. Among the 183 resistant genes detected, 54 isolates produced extended spectrum β-lactamases (ESBL), of which blaCTX-M-15 was predominant (37 isolates; 68.5%). A KPC-3 carbapenemase-producing K. oxytoca was identified (n = 1), with blaKPC-3 included in a transposon Tn4401 isoform b. A higher number of virulence genes (VG) (19 genes) was found in the E. coli 5301 (O25b-ST131-B2) isolate compared with a commensal E. coli 5281 (O25b-ST410-A) (six genes). Both shared five VG [Enterobactin; Aerobactin, CFA/1 (clade α); Type1 (clade γ1); Type IV]. In conclusion, this work highlights the role of relevant clinical bacteria in WWTPs, such as KPC-3-producing K. oxytoca, and, for the first time, a CTX-M-15-producing Ochromobactrum intermedium, a human opportunistic pathogen, and a SED-1-producing Citrobacter farmeri, an uncommon CTX-M-type extended-spectrum beta-lactamase. Full article
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Communication
Genomic Analysis of Antimicrobial Resistance Genotype-to-Phenotype Agreement in Helicobacter pylori
Microorganisms 2021, 9(1), 2; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9010002 - 22 Dec 2020
Cited by 5 | Viewed by 1280
Abstract
Antimicrobial resistance (AMR) in Helicobacter pylori is increasing and can result in treatment failure and inappropriate antibiotic usage. This study used whole genome sequencing (WGS) to comprehensively analyze the H. pylori resistome and phylogeny in order to characterize Israeli H. pylori. Israeli [...] Read more.
Antimicrobial resistance (AMR) in Helicobacter pylori is increasing and can result in treatment failure and inappropriate antibiotic usage. This study used whole genome sequencing (WGS) to comprehensively analyze the H. pylori resistome and phylogeny in order to characterize Israeli H. pylori. Israeli H. pylori isolates (n = 48) underwent antimicrobial susceptibility testing (AST) against five antimicrobials and WGS analysis. Literature review identified 111 mutations reported to correlate with phenotypic resistance to these antimicrobials. Analysis was conducted via our in-house bioinformatics pipeline targeting point mutations in the relevant genes (pbp1A, 23S rRNA, gyrA, rdxA, frxA, and rpoB) in order to assess genotype-to-phenotype correlation. Resistance rates of study isolates were as follows: clarithromycin 54%, metronidazole 31%, amoxicillin 10%, rifampicin 4%, and levofloxacin 2%. Genotype-to-phenotype correlation was inconsistent; for every analyzed gene at least one phenotypically susceptible isolate was found to have a mutation previously associated with resistance. This was also observed regarding mutations commonly used in commercial kits to diagnose AMR in H. pylori cases. Furthermore, 11 novel point mutations associated with a resistant phenotype were detected. Analysis of a unique set of H. pylori isolates demonstrates that inferring resistance phenotypes from WGS in H. pylori remains challenging and should be optimized further. Full article
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Article
Unravelling the Features of Success of VIM-Producing ST111 and ST235 Pseudomonas aeruginosa in a Greek Hospital
Microorganisms 2020, 8(12), 1884; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8121884 - 28 Nov 2020
Cited by 3 | Viewed by 834
Abstract
The objective of this study was to analyze the characteristics that contribute to the successful dissemination of VIM-producing Pseudomonas aeruginosa (P. aeruginosa), belonging to ST111 and ST235, in a Greek hospital. A total of 120 non-repetitive P. aeruginosa, which had [...] Read more.
The objective of this study was to analyze the characteristics that contribute to the successful dissemination of VIM-producing Pseudomonas aeruginosa (P. aeruginosa), belonging to ST111 and ST235, in a Greek hospital. A total of 120 non-repetitive P. aeruginosa, which had meropenem minimal inhibitory concentrations (MICs) greater than 2 mg/L, were studied. VIM-encoding genes were amplified and sequenced within their integrons. Isolates were typed by multilocus sequence typing (MLST). Six VIM-producers, representative of different integron structures and sequence types (STs), were completely sequenced using Illumina platform. Sixty-one P. aeruginosa were confirmed to produce VIM-type carbapenemases. ST111 dominated (n = 34) among VIM-producers, while 15 VIM-producers belonged to ST235. The blaVIM-like genes were located in three integron types, including In59, In595 and In1760, which were integrated into P. aeruginosa chromosomes. Whole genome sequencing (WGS) data demonstrated that ST111 and ST235 MBL producers carried several resistance and virulence genes. Additionally, the presence of type I-C and type I-E clustered regularly interspaced short palindromic repeats (CRISPR)/Cas locus was observed in ST235 and ST395 isolates, respectively. In conclusion, our findings confirmed the clonal spread of ST111 P. aeruginosa, carrying the VIM-2-encoding integron In59, in the University Hospital of Larissa (UHL). In addition, they highlighted the important role of high-risk clones, ST111 and ST235, in the successful dissemination and establishment into hospital settings of clinically important pathogens carrying resistance determinants. Full article
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Article
Antimicrobial Resistance Gene Detection and Plasmid Typing Among Multidrug Resistant Enterococci Isolated from Freshwater Environment
Microorganisms 2020, 8(9), 1338; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8091338 - 02 Sep 2020
Cited by 2 | Viewed by 927
Abstract
In this study, mechanisms of antimicrobial resistance (AR) as well as the abundance and diversity of plasmids were determined among multidrug resistant (MDR) enterococci from surface water in GA, USA. A total of 51 enterococci isolates were screened for the presence of 27 [...] Read more.
In this study, mechanisms of antimicrobial resistance (AR) as well as the abundance and diversity of plasmids were determined among multidrug resistant (MDR) enterococci from surface water in GA, USA. A total of 51 enterococci isolates were screened for the presence of 27 AR genes conferring resistance to ciprofloxacin, erythromycin, tylosin, kanamycin, streptomycin, lincomycin, Quinupristin/Dalfopristin (Q/D), and tetracycline. A plasmid classification system based on replication genes was used to detect 19 defined Gram-positive plasmid replicon families. Twelve genes were identified as conferring resistance to erythromycin and tylosin (erm(B) and erm(C)), kanamycin (aph(3′)-IIIa), streptomycin (ant(6)-Ia), lincomycin (lnu(B)), Q/D (vat(E)), ciprofloxacin (qnrE. faecalis), and tetracycline (tet(K), tet(L), tet(M), tet(O) and tet(S)). Twelve different rep-families were identified in two-thirds of the isolates. While AR genes commonly found in human and animals were detected in this study among environmental enterococci, resistance genes could not be determined for many of the isolates, which indicates that diverse AR mechanisms exist among enterococci, and the understanding of AR mechanisms for environmental enterococci is limited. Diverse rep-families were identified among the enterococci recovered from the aquatic environment, and these rep-families appear to be quite different from those recovered from other sources. This work expands knowledge of AR gene reservoirs and enterococcal plasmids across a wider range of environments. Full article

Review

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Review
The History of Colistin Resistance Mechanisms in Bacteria: Progress and Challenges
Microorganisms 2021, 9(2), 442; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9020442 - 20 Feb 2021
Cited by 7 | Viewed by 1268
Abstract
Since 2015, the discovery of colistin resistance genes has been limited to the characterization of new mobile colistin resistance (mcr) gene variants. However, given the complexity of the mechanisms involved, there are many colistin-resistant bacterial strains whose mechanism remains unknown and [...] Read more.
Since 2015, the discovery of colistin resistance genes has been limited to the characterization of new mobile colistin resistance (mcr) gene variants. However, given the complexity of the mechanisms involved, there are many colistin-resistant bacterial strains whose mechanism remains unknown and whose exploitation requires complementary technologies. In this review, through the history of colistin, we underline the methods used over the last decades, both old and recent, to facilitate the discovery of the main colistin resistance mechanisms and how new technological approaches may help to improve the rapid and efficient exploration of new target genes. To accomplish this, a systematic search was carried out via PubMed and Google Scholar on published data concerning polymyxin resistance from 1950 to 2020 using terms most related to colistin. This review first explores the history of the discovery of the mechanisms of action and resistance to colistin, based on the technologies deployed. Then we focus on the most advanced technologies used, such as MALDI-TOF-MS, high throughput sequencing or the genetic toolbox. Finally, we outline promising new approaches, such as omics tools and CRISPR-Cas9, as well as the challenges they face. Much has been achieved since the discovery of polymyxins, through several innovative technologies. Nevertheless, colistin resistance mechanisms remains very complex. Full article
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Review
Diversity and Distribution of Resistance Markers in Pseudomonas aeruginosa International High-Risk Clones
Microorganisms 2021, 9(2), 359; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9020359 - 12 Feb 2021
Cited by 3 | Viewed by 798
Abstract
Pseudomonas aeruginosa high-risk clones are disseminated worldwide and they are common causative agents of hospital-acquired infections. In this review, we will summarize available data of high-risk P. aeruginosa clones from confirmed outbreaks and based on whole-genome sequence data. Common feature of high-risk clones [...] Read more.
Pseudomonas aeruginosa high-risk clones are disseminated worldwide and they are common causative agents of hospital-acquired infections. In this review, we will summarize available data of high-risk P. aeruginosa clones from confirmed outbreaks and based on whole-genome sequence data. Common feature of high-risk clones is the production of beta-lactamases and among metallo-beta-lactamases NDM, VIM and IMP types are widely disseminated in different sequence types (STs), by contrast FIM type has been reported in ST235 in Italy, whereas GIM type in ST111 in Germany. In the case of ST277, it is most frequently detected in Brazil and it carries a resistome linked to blaSPM. Colistin resistance develops among P. aeruginosa clones in a lesser extent compared to other resistance mechanisms, as ST235 strains remain mainly susceptible to colistin however, some reports described mcr positive P. aeurigonsa ST235. Transferable quinolone resistance determinants are detected in P. aeruginosa high-risk clones and aac(6′)-Ib-cr variant is the most frequently reported as this determinant is incorporated in integrons. Additionally, qnrVC1 was recently detected in ST773 in Hungary and in ST175 in Spain. Continuous monitoring and surveillance programs are mandatory to track high-risk clones and to analyze emergence of novel clones as well as novel resistance determinants. Full article
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Other

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Brief Report
Cell Wall Proteome Profiling of a Candida albicans Fluconazole-Resistant Strain from a Lebanese Hospital Patient Using Tandem Mass Spectrometry—A Pilot Study
Microorganisms 2021, 9(6), 1161; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9061161 - 28 May 2021
Viewed by 1377
Abstract
Candida albicans is an opportunistic pathogenic fungus responsible for high mortality rates in immunocompromised individuals. Azole drugs such as fluconazole are the first line of therapy in fungal infection treatment. However, resistance to azole treatment is on the rise. Here, we employ a [...] Read more.
Candida albicans is an opportunistic pathogenic fungus responsible for high mortality rates in immunocompromised individuals. Azole drugs such as fluconazole are the first line of therapy in fungal infection treatment. However, resistance to azole treatment is on the rise. Here, we employ a tandem mass spectrometry approach coupled with a bioinformatics approach to identify cell wall proteins present in a fluconazole-resistant hospital isolate upon drug exposure. The isolate was previously shown to have an increase in cell membrane ergosterol and cell wall chitin, alongside an increase in adhesion, but slightly attenuated in virulence. We identified 50 cell wall proteins involved in ergosterol biosynthesis such as Erg11, and Erg6, efflux pumps such as Mdr1 and Cdr1, adhesion proteins such as Als1, and Pga60, chitin deposition such as Cht4, and Crh11, and virulence related genes including Sap5 and Lip9. Candidial proteins identified in this study go a long way in explaining the observed phenotypes. Our pilot study opens the way for a future large-scale analysis to identify novel proteins involved in drug-resistance mechanisms. Full article
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