Phylogenomics, epigenomics, virulome and mobilome of Gram-negative bacteria co-resistant to carbapenems and polymyxins: a One Health systematic review and meta-analyses. - Related Documents




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185101.0000Phylogenomics, epigenomics, virulome and mobilome of Gram-negative bacteria co-resistant to carbapenems and polymyxins: a One Health systematic review and meta-analyses. Gram-negative bacteria (GNB) continue to develop resistance against important antibiotics including last-resort ones such as carbapenems and polymyxins. An analysis of GNB with co-resistance to carbapenems and polymyxins from a One Health perspective is presented. Data of species name, country, source of isolation, resistance genes (ARGs), plasmid type, clones and mobile genetic elements (MGEs) were deduced from 129 articles from January 2016 to March 2021. Available genomes and plasmids were obtained from PATRIC and NCBI. Resistomes and methylomes were analysed using BAcWGSTdb and REBASE whilst Kaptive was used to predict capsule typing. Plasmids and other MEGs were identified using MGE Finder and ResFinder. Phylogenetic analyses were done using RAxML and annotated with MEGA 7. A total of 877 isolates, 32 genomes and 44 plasmid sequences were analysed. Most of these isolates were reported in Asian countries and were isolated from clinical, animal and environmental sources. Colistin resistance was mostly mediated by mgrB inactivation (37%; n = 322) and mcr-1 (36%; n = 312), while OXA-48/181 was the most reported carbapenemase. IncX and IncI were the most common plasmids hosting carbapenemases and mcr genes. The isolates were co-resistant to other antibiotics, with floR (chloramphenicol) and fosA3 (fosfomycin) being common; E. coli ST156 and K. pneumoniae ST258 strains were common globally. Virulence genes and capsular KL-types were also detected. Type I, II, III and IV restriction modification systems were detected, comprising various MTases and restriction enzymes. The escalation of highly resistant isolates drains the economy due to untreatable bacterial infections, which leads to increasing global mortality rates and healthcare costs.202235129271
168610.9998Resistome of carbapenem- and colistin-resistant Klebsiella pneumoniae clinical isolates. The emergence and dissemination of carbapenemases, bacterial enzymes able to inactivate most β-lactam antibiotics, in Enterobacteriaceae is of increasing concern. The concurrent spread of resistance against colistin, an antibiotic of last resort, further compounds this challenge further. Whole-genome sequencing (WGS) can play a significant role in the rapid and accurate detection/characterization of existing and emergent resistance determinants, an essential aspect of public health surveillance and response activities to combat the spread of antimicrobial resistant bacteria. In the current study, WGS data was used to characterize the genomic content of antimicrobial resistance genes, including those encoding carbapenemases, in 10 multidrug-resistant Klebsiella pneumoniae isolates from Pakistan. These clinical isolates represented five sequence types: ST11 (n = 3 isolates), ST14 (n = 3), ST15 (n = 1), ST101 (n = 2), and ST307 (n = 1). Resistance profiles against 25 clinically-relevant antimicrobials were determined by broth microdilution; resistant phenotypes were observed for at least 15 of the 25 antibiotics tested in all isolates except one. Specifically, 8/10 isolates were carbapenem-resistant and 7/10 isolates were colistin-resistant. The blaNDM-1 and blaOXA-48 carbapenemase genes were present in 7/10 and 5/10 isolates, respectively; including 2 isolates carrying both genes. No plasmid-mediated determinants for colistin resistance (e.g. mcr) were detected, but disruptions and mutations in chromosomal loci (i.e. mgrB and pmrB) previously reported to confer colistin resistance were observed. A blaOXA-48-carrying IncL/M-type plasmid was found in all blaOXA-48-positive isolates. The application of WGS to molecular epidemiology and surveillance studies, as exemplified here, will provide both a more complete understanding of the global distribution of MDR isolates and a robust surveillance tool useful for detecting emerging threats to public health.201829883490
168520.9998Molecular epidemiology and mechanisms of carbapenem and colistin resistance in Klebsiella and other Enterobacterales from treated wastewater in Croatia. Among the most problematic bacteria with clinical relevance are the carbapenem-resistant Enterobacterales (CRE), as there are very limited options for their treatment. Treated wastewater can be a route for the release of these bacteria into the environment and the population. The aim of this study was to isolate CRE from treated wastewater from the Zagreb wastewater treatment plant and to determine their phenotypic and genomic characteristics. A total of 200 suspected CRE were isolated, 148 of which were confirmed as Enterobacterales by MALDI-TOF MS. The predominant species was Klebsiella spp. (n = 47), followed by Citrobacter spp. (n = 40) and Enterobacter cloacae complex (cplx.) (n = 35). All 148 isolates were carbapenemase producers with a multidrug-resistant phenotype. Using multi-locus sequence typing and whole-genome sequencing (WGS), 18 different sequence types were identified among these isolates, 14 of which were associated with human-associated clones. The virulence gene analysis of the sequenced Klebsiella isolates (n = 7) revealed their potential pathogenicity. PCR and WGS showed that the most frequent carbapenemase genes in K. pneumoniae were bla(OXA-48) and bla(NDM-1), which frequently occurred together, while bla(KPC-2) together with bla(NDM-1) was mainly detected in K. oxytoca, E. cloacae cplx. and Citrobacter spp. Colistin resistance was observed in 40% of Klebsiella and 57% of Enterobacter isolates. Underlying mechanisms identified by WGS include known and potentially novel intrinsic mechanisms (point mutations in the pmrA/B, phoP/Q, mgrB and crrB genes) and acquired mechanisms (mcr-4.3 gene). The mcr-4.3 gene was identified for the first time in K. pneumoniae and is probably located on the conjugative IncHI1B plasmid. In addition, WGS analysis of 13 isolates revealed various virulence genes and resistance genes to other clinically relevant antibiotics as well as different plasmids possibly associated with carbapenemase genes. Our study demonstrates the important role that treated municipal wastewater plays in harboring and spreading enterobacterial pathogens that are resistant to last-resort antibiotics.202438479059
157430.9997Plethora of Resistance Genes in Carbapenem-Resistant Gram-Negative Bacteria in Greece: No End to a Continuous Genetic Evolution. Carbapenem-resistant Gram-negative bacteria are a public health threat that requires urgent action. The fact that these pathogens commonly also harbor resistance mechanisms for several other antimicrobial classes further reduces patient treatment options. The present study aimed to provide information regarding the multidrug resistance genetic background of carbapenem-resistant Gram-negative bacteria in Central Greece. Strains from a tertiary care hospital, collected during routine practice, were characterized using a DNA microarray-based assay. Various different resistance determinants for carbapenems, other beta-lactams, aminoglycosides, quinolones, trimethoprim, sulfonamides and macrolides were detected among isolates of the same sequence type. Eighteen different multidrug resistance genomic profiles were identified among the twenty-four K. pneumoniae ST258, seven different profiles among the eight K. pneumoniae ST11, four profiles among the six A. baumannii ST409 and two among the three K. oxytoca. This report describes the multidrug resistance genomic background of carbapenem-resistant Gram-negative bacteria from a tertiary care hospital in Central Greece, providing evidence of their continuous genetic evolution.202235056608
166740.9997Colistin Resistance Gene mcr-8 in a High-Risk Sequence Type 15 Klebsiella pneumoniae Isolate from Kenya. The emergence and rise of mobile colistin resistance genes are of great global concern due to the ease of transfer of resistance to other bacteria. This report describes the genome of a colistin- and multidrug-resistant Klebsiella pneumoniae isolate bearing mcr-8, obtained from a hospitalized patient in Kenya.202032972937
168950.9997Occurrence and Characteristics of Mcrs among Gram-Negative Bacteria Causing Bloodstream Infections of Infant Inpatients between 2006 and 2019 in China. The aim of this study was to determine the occurrence of mobilized colistin resistance (mcr) genes in Gram-negative bacteria causing bloodstream infections of child inpatients in China. Bacteria were collected between 2006 and 2019 in a maternal and child health hospital, and mcr genes were screened by PCR. Five of 252 isolates were mcr-positive, including one mcr-1-positive colistin-resistant Escherichia coli isolate, two mcr-9-positive colistin-susceptible Salmonella enterica isolates, and two mcr-9-positive colistin-susceptible Enterobacter hormaechei isolates. These were obtained from two neonate and three infant patients admitted between 2009 and 2018. The E. coli isolate was obtained from a neonate aged 20 min, suggestive of a possible mother-to-neonate transmission. The five mcr-positive isolates were multidrug resistant, and two S. enterica and one E. hormaechei isolate showed a hypervirulent phenotype compared to a hypervirulent Klebsiella pneumoniae type strain in a Galleria mellonella infection model. The mcr-1 gene was carried by an IncX4-type pA1-like epidemic plasmid, and the mcr-9 gene was detected on IncHI2/2A-type novel plasmids co-carrying multiple resistance genes. The four IncHI2/2A-type plasmids shared a backbone and a high similarity (≥77% coverage and ≥ 90% nucleotide identity), suggesting that they were derived from a common ancestor with cross-species transmission and have circulated locally over a long period. The conjugation assay showed that the mcr-1-encoding plasmid and one mcr-9-encoding plasmid were self-transmissible to E. coli with high conjugation frequencies. Our findings demonstrate that mcr genes have disseminated in the community and/or hospitals, mediated by epidemic/endemic plasmids over a long period. The study shows that continuous monitoring of mcr genes is imperative for understanding and tackling their dissemination. IMPORTANCE Antimicrobial resistance, especially the spread of carbapenemase-producing Enterobacteriaceae (CPE), represents one of the largest challenges to One Health coverage of environmental, animal, and human sectors. Colistin is one of the last-line antibiotics for clinical treatment of CPE. However, the emergence of the mobilized colistin resistance (mcr) gene largely threatens the usage of colistin in the clinical setting. In this study, we investigated the existence of mcr genes in 252 Gram-negative bacteria collected between 2006 and 2019 which caused bloodstream infections of child inpatients in China. We found a high prevalence of mcr carriage among children inpatients in the absence of professional exposure, and mcr might have widely disseminated in the community via different routes. This study emphasizes the importance of rational use of colistin in the One Health frame, and highlights both the urgent need for understanding the prevalence and dissemination of mcr genes in different populations and the importance of effective measures to control their spread.202235138190
166860.9997Detection of OXA-181 Carbapenemase in Shigella flexneri. We report the detection of OXA-181 carbapenemase in an azithromycin-resistant Shigella spp. bacteria in an immunocompromised patient. The emergence of OXA-181 in Shigella spp. bacteria raises concerns about the global dissemination of carbapenem resistance in Enterobacterales and its implications for the treatment of infections caused by Shigella bacteria.202438666725
167870.9997Molecular characterization and descriptive analysis of carbapenemase-producing Gram-negative rod infections in Bogota, Colombia. In this study, the genetic differences and clinical impact of the carbapenemase-encoding genes among the community and healthcare-acquired infections were assessed. This retrospective, multicenter cohort study was conducted in Colombia and included patients infected with carbapenem-resistant Gram-negative rods between 2017 and 2021. Carbapenem resistance was identified by Vitek, and carbapenemase-encoding genes were identified by whole-genome sequencing (WGS) to classify the alleles and sequence types (STs). Descriptive statistics were used to determine the association of any pathogen or gene with clinical outcomes. A total of 248 patients were included, of which only 0.8% (2/248) had community-acquired infections. Regarding the identified bacteria, the most prevalent pathogens were Pseudomonas aeruginosa and Klebsiella pneumoniae. In the WGS analysis, 228 isolates passed all the quality criteria and were analyzed. The principal carbapenemase-encoding gene was blaKPC, specifically blaKPC-2 [38.6% (88/228)] and blaKPC-3 [36.4% (83/228)]. These were frequently detected in co-concurrence with blaVIM-2 and blaNDM-1 in healthcare-acquired infections. Notably, the only identified allele among community-acquired infections was blaKPC-3 [50.0% (1/2)]. In reference to the STs, 78 were identified, of which Pseudomonas aeruginosa ST111 was mainly related to blaKPC-3. Klebsiella pneumoniae ST512, ST258, ST14, and ST1082 were exclusively associated with blaKPC-3. Finally, no particular carbapenemase-encoding gene was associated with worse clinical outcomes. The most identified genes in carbapenemase-producing Gram-negative rods were blaKPC-2 and blaKPC-3, both related to gene co-occurrence and diverse STs in the healthcare environment. Patients had several systemic complications and poor clinical outcomes that were not associated with a particular gene.IMPORTANCEAntimicrobial resistance is a pandemic and a worldwide public health problem, especially carbapenem resistance in low- and middle-income countries. Limited data regarding the molecular characteristics and clinical outcomes of patients infected with these bacteria are available. Thus, our study described the carbapenemase-encoding genes among community- and healthcare-acquired infections. Notably, the co-occurrence of carbapenemase-encoding genes was frequently identified. We also found 78 distinct sequence types, of which two were novel Pseudomonas aeruginosa, which could represent challenges in treating these infections. Our study shows that in low and middle-income countries, such as Colombia, the burden of carbapenem resistance in Gram-negative rods is a concern for public health, and regardless of the allele, these infections are associated with poor clinical outcomes. Thus, studies assessing local epidemiology, prevention strategies (including trials), and underpinning genetic mechanisms are urgently needed, especially in low and middle-income countries.202438629835
189280.9997Colistin Resistance Mediated by Mcr-3-Related Phosphoethanolamine Transferase Genes in Aeromonas Species Isolated from Aquatic Environments in Avaga and Pakro Communities in the Eastern Region of Ghana. PURPOSE: Colistin is classified by the World Health Organization (WHO) as a critically important and last-resort antibiotic for the treatment of infections caused by carbapenem-resistant bacteria. However, colistin resistance mediated by chromosomal mutations or plasmid-linked mobilized colistin resistance (mcr) genes has emerged. METHODS: Thirteen mcr-positive Aeromonas species isolated from water samples collected in Eastern Ghana were analyzed using whole-genome sequencing (WGS). Antimicrobial susceptibility was tested using the broth microdilution method. Resistome analysis was performed in silico using a web-based platform. RESULTS: The minimum inhibitory concentration (MIC) of colistin for all except three isolates was >4 µg/mL. Nine new sequence types were identified and whole-genome analysis revealed that the isolates harbored genes (mcr-3-related genes) that code for Lipid A phosphoethanolamine transferases on their chromosomes. BLAST analysis indicated that the amino acid sequences of the mcr-3-related genes detected varied from those previously reported and shared 79.04-99.86% nucleotide sequence identity with publicly available mcr-3 variants and mcr-3-related phosphoethanolamine transferases. Analysis of the genetic context of mcr-3-related genes revealed that the genetic environment surrounding mcr-3-related genes was diverse among the different species of Aeromonas but conserved among isolates of the same species. Mcr-3-related-gene-IS-mcr-3-related-gene segment was identified in three Aeromonas caviae strains. CONCLUSION: The presence of mcr-3-related genes close to insertion elements is important for continuous monitoring to better understand how to control the mobilization and dissemination of antibiotic resistance genes.202439050833
184590.9997Plasmid-mediated colistin resistance in Latin America and Caribbean: A systematic review. A systematic review was performed in order to integrate and synthesize available information on mcr genes dissemination in Latin America. Four databases were searched for articles reporting plasmid-mediated colistin resistance between bacteria isolated from countries of Latin America and the Caribbean. Abstract books of scientific events realized in each region were also examined. After search and selection, 48 studies that included 18,705 isolates recovered between 2000 and 2018 were evaluated. The overall frequency of mcr genes in Latin America was 2.9% (550/18,705), with IncX4 plasmids shown to be the key vectors responsible for the dissemination of genes within the continent. Brazil, Bolivia and Argentina were the countries with the highest number of mcr-positive isolates, and only Colombia (mcr-5) and Brazil (mcr-3) presented mcr genes other than type 1. Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica serovar Typhimurium were mainly found to carry the gene within the continent and these microorganisms showed high susceptibility to ertapenem, meropenem, piperacillin/tazobactam, fosfomycin and tigecycline. This review showed that the mcr gene is circulating in several countries of Latin America. Thus, it is important to encourage microbiological and molecular surveillance programs to avoid the spread of these genes within and outside the continent.201931336179
1856100.9997Whole-Genome Sequencing-Based Species Classification, Multilocus Sequence Typing, and Antimicrobial Resistance Mechanism Analysis of the Enterobacter cloacae Complex in Southern China. Members of the Enterobacter cloacae complex (ECC) are important opportunistic nosocomial pathogens that are associated with a great variety of infections. Due to limited data on the genome-based classification of species and investigation of resistance mechanisms, in this work, we collected 172 clinical ECC isolates between 2019 and 2020 from three hospitals in Zhejiang, China and performed a retrospective whole-genome sequencing to analyze their population structure and drug resistance mechanisms. Of the 172 ECC isolates, 160 belonged to 9 classified species, and 12 belonged to unclassified species based on ANI analysis. Most isolates belonged to E. hormaechei (45.14%) followed by E. kobei (13.71%), which contained 126 STs, including 62 novel STs, as determined by multilocus sequence typing (MLST) analysis. Pan-genome analysis of the two ECC species showed that they have an "open" tendency, which indicated that their Pan-genome increased considerably with the addition of new genomes. A total of 80 resistance genes associated with 11 antimicrobial agent categories were identified in the genomes of all the isolates. The most prevailing resistance genes (12/29, 41.38%) were related to β-lactams followed by aminoglycosides. A total of 247 β-lactamase genes were identified, of which the bla(ACT) genes were the most dominant (145/247, 58.70%), followed by the bla(TEM) genes (21/247, 8.50%). The inherent ACT type β-lactamase genes differed among different species. bla(ACT-2) and bla(ACT-3) were only present in E. asburiae, while bla(ACT-9), bla(ACT-12), and bla(ACT-6) exclusively appeared in E. kobei, E. ludwigii, and E. mori. Among the six carbapenemase-encoding genes (bla(NDM-1), bla(NDM-5), bla(IMP-1), bla(IMP-4), bla(IMP-26), and bla(KPC-2)) identified, two (bla(NDM-1) and bla(IMP-1)) were identified in an ST78 E. hormaechei isolate. Comparative genomic analysis of the carbapenemase gene-related sequences was performed, and the corresponding genetic structure of these resistance genes was analyzed. Genome-wide molecular characterization of the ECC population and resistance mechanism would offer valuable insights into the effective management of ECC infection in clinical settings. IMPORTANCE The presence and emergence of multiple species/subspecies of ECC have led to diversity and complications at the taxonomic level, which impedes our further understanding of the epidemiology and clinical significance of species/subspecies of ECC. Accurate identification of ECC species is extremely important. Also, it is of great importance to study the carbapenem-resistant genes in ECC and to further understand the mechanism of horizontal transfer of the resistance genes by analyzing the surrounding environment around the genes. The occurrence of ECC carrying two MBL genes also indicates that the selection pressure of bacteria is further increased, suggesting that we need to pay special attention to the emergence of such bacteria in the clinic.202236350178
1571110.9997Klebsiella pneumoniae ST147 harboring bla(NDM-1), multidrug resistance and hypervirulence plasmids. The spread of hypervirulent (hv) and carbapenem-/multidrug-resistant Klebsiella pneumoniae is an emerging problem in healthcare settings. The New Delhi metallo-β-lactamase-1 (bla(NDM-1)) is found in Enterobacteriaceae including K. pneumoniae. The bla(NDM-1) is capable of hydrolyzing β-lactam antibiotics which are used for treatment of severe infections caused by multidrug-resistant Gram-negative bacteria. This is associated with the unacceptably high mortality rate in immunocompromised burn injury patients. This study reports on the characterization of bla(NDM-1) gene and virulence factors in hv carbapenem-/multidrug-resistant K. pneumoniae ST147 in the burns unit of a tertiary teaching hospital during routine surveillance. Two K. pneumoniae strains were obtained from wounds of burn-infected patients from May 2020 to July 2021. The hypervirulence genes and genetic context of the bla(NDM-1) gene and mobile genetic elements potentially involved in the transposition of the gene were analyzed. We identified a conserved genetic background and an IS26 and open reading frame flanking the bla(NDM-1) gene that could suggest its involvement in the mobilization of the gene. The plasmid harbored additional antibiotic resistance predicted regions that were responsible for resistance to almost all the routinely used antibiotics. To ensure the identification of potential outbreak strains during routine surveillance, investigations on resistance genes and their environment in relation to evolution are necessary for molecular epidemiology.IMPORTANCEData obtained from this study will aid in the prompt identification of disease outbreaks including evolving resistance and virulence of the outbreak bacteria. This will help establish and implement antimicrobial stewardship programs and infection prevention protocols in fragile health systems in countries with limited resources. Integration of molecular surveillance and translation of whole-genome sequencing in routine diagnosis will provide valuable data for control of infection. This study reports for the first time a high-risk clone K. pneumoniae ST147 with hypervirulence and multidrug-resistance features in Ghana.202438315028
1684120.9997Plasmid-encoded gene duplications of extended-spectrum β-lactamases in clinical bacterial isolates. INTRODUCTION: The emergence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is an urgent and alarming One Health problem. This study aimed to investigate duplications of plasmid-encoded ESBL genes and their impact on antimicrobial resistance (AMR) phenotypes in clinical and screening isolates. METHODS: Multi-drug-resistant bacteria from hospitalized patients were collected during routine clinical surveillance from January 2022 to June 2023, and their antimicrobial susceptibility patterns were determined. Genotypes were extracted from long-read whole-genome sequencing data. Furthermore, plasmids and other mobile genetic elements associated with ESBL genes were characterized, and the ESBL genes were correlated to ceftazidime minimal inhibitory concentration (MIC). RESULTS: In total, we identified four cases of plasmid-encoded ESBL gene duplications that match four genetically similar plasmids during the 18-month surveillance period: five Escherichia coli and three Klebsiella pneumoniae isolates. As the ESBL genes were part of transposable elements, the surrounding sequence regions were duplicated as well. In-depth analysis revealed insertion sequence (IS)-mediated transposition mechanisms. Isolates with duplicated ESBL genes exhibited a higher MIC for ceftazidime in comparison to isolates with a single gene copy (3-256 vs. 1.5-32 mg/L, respectively). CONCLUSION: ESBL gene duplications led to an increased phenotypic resistance against ceftazidime. Our data suggest that ESBL gene duplications by an IS-mediated transposition are a relevant mechanism for how AMR develops in the clinical setting and is part of the microevolution of plasmids.202438469349
1575130.9997Widespread transfer of resistance genes between bacterial species in an intensive care unit: implications for hospital epidemiology. A transferable plasmid encoding SHV-12 extended-spectrum beta-lactamase, TEM-116, and aminoglycoside resistance was responsible for two sequential clonal outbreaks of Enterobacter cloacae and Acinetobacter baumannii bacteria. A similar plasmid was present among isolates of four different bacterial species. Recognition of plasmid transfer is crucial for control of outbreaks of multidrug-resistant nosocomial pathogens.200516145160
1842140.9997Emergence of mcr-9.1 in Extended-Spectrum-β-Lactamase-Producing Clinical Enterobacteriaceae in Pretoria, South Africa: Global Evolutionary Phylogenomics, Resistome, and Mobilome. Extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae are critical-priority pathogens that cause substantial fatalities. With the emergence of mobile mcr genes mediating resistance to colistin in Enterobacteriaceae, clinicians are now left with few therapeutic options. Eleven clinical Enterobacteriaceae strains with resistance to cephems and/or colistin were genomically analyzed to determine their resistomes, mobilomes, and evolutionary relationships to global strains. The global phylogenomics of mcr genes and mcr-9.1-bearing genomes were further analyzed. Ten isolates were ESBL positive. The isolates were multidrug resistant and phylogenetically related to global clones but distant from local strains. Multiple resistance genes, including bla (CTX-M-15) bla (TEM-1), and mcr-9.1, were found in single isolates; ISEc9, IS19, and Tn3 transposons bracketed bla (CTX-M-15) and bla (TEM-1) Common plasmid types included IncF, IncH, and ColRNAI. mcr-9 was of close sequence identity to mcr-3, mcr-5, mcr-7, mcr-8, and mcr-10. Genomes bearing mcr-9.1 clustered into six main phyletic groups (A to F), with those of this study belonging to clade B. Enterobacter species and Salmonella species are the main hosts of mcr-9.1 globally, although diverse promiscuous plasmids disseminate mcr-9.1 across different bacterial species. Emergence of mcr-9.1 in ESBL-producing Enterobacteriaceae in South Africa is worrying, due to the restricted therapeutic options. Intensive One Health molecular surveillance might discover other mcr alleles and inform infection management and antibiotic choices.IMPORTANCE Colistin is currently the last-resort antibiotic for difficult-to-treat bacterial infections. However, colistin resistance genes that can move from bacteria to bacteria have emerged, threatening the safe treatment of many bacterial infections. One of these genes, mcr-9.1, has emerged in South Africa in bacteria that are multidrug resistant, further limiting treatment options for clinicians. In this work, we show that this new gene is disseminating worldwide through Enterobacter and Salmonella species through multiple plasmids. This worrying observation requires urgent action to prevent further escalation of this gene in South Africa and Africa.202032430406
1680150.9997Emergence of carbapenem resistant gram-negative pathogens with high rate of colistin resistance in Egypt: A cross sectional study to assess resistance trends during the COVID-19 pandemic. The current study investigated the temporal phenotypic and genotypic antimicrobial resistance (AMR) trends among multi-drug resistant and carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa recovered from Egyptian clinical settings between 2020 and 2021. Bacterial identification and antimicrobial sensitivity of 111 clinical isolates against a panel of antibiotics were performed. Molecular screening for antibiotic resistance determinants along with integrons and associated gene cassettes was implemented. An alarming rate (98.2%) of these isolates were found to be phenotypically resistant to carbapenem. Although 23.9 % K. pneumoniae isolates were phenotypically resistant to colistin, no mobile colistin resistance (mcr) genes were detected. Among carbapenem-resistant isolates, bla(NDM) and bla(OXA-48)-like were the most prevalent genetic determinants and were significantly overrepresented among K. pneumoniae. Furthermore, 84.78% of K. pneumoniae isolates co-produced these two carbapenemase genes. The plasmid-mediated quinolone resistance genes (qnrS and qnrB) were detected among the bacterial species and were significantly more prevalent among K. pneumoniae. Moreover, Class 1 integron was detected in 82% of the bacterial isolates. This study alarmingly reveals elevated resistance to last-resort antibiotics such as carbapenems as well as colistin which impose a considerable burden in the health care settings in Egypt. Our future work will implement high throughput sequencing-based antimicrobial resistance surveillance analysis for characterization of novel AMR determinants. This information could be applied as a step forward to establish a robust antibiotic stewardship program in Egyptian clinical settings, thereby addressing the rising challenges of AMR.202438494251
1630160.9997One Health study of mobile colistin resistance (mcr) in Salmonella enterica in Canada, 2017-2022. Colistin is a last-resort treatment for highly drug-resistant bacterial infections. Of 47,184 Salmonella isolates collected from 2017 to 2022 in Canada from human and animal/food sources, mobile colistin resistance (mcr) variants conferring colistin resistance were detected exclusively in humans (n = 15). These variants were mcr-1.1 (n = 7), mcr-3.1 (n = 5), mcr-3.2 (n = 2), and mcr-1.2 (n = 1). The most common mcr-containing serotypes were I 4,[5],12:i:- (n = 8) and Typhimurium (n = 3). The proportion of Salmonella carrying mcr genes remains low in Canada (0.03%). IMPORTANCE: Colistin can be used in combination with other drugs as salvage therapy for extensively drug-resistant infections. If mobile colistin resistance (mcr) becomes widely disseminated in Enterobacterales, colistin will no longer be an option for salvage therapy in otherwise untreatable infections. While colistin is not commonly used to treat human Salmonella infections, Salmonella represents an important reservoir of mcr genes that may be transmitted to other gram-negative bacteria. Our aim was to determine the occurrence of mcr genes in Salmonella isolates collected from humans, food animals, and retail meats in Canada.202540387317
887170.9997Characterization of fosfomycin resistance and molecular epidemiology among carbapenem-resistant Klebsiella pneumoniae strains from two tertiary hospitals in China. BACKGROUND: Fosfomycin has been proven to be a vital choice to treat infection caused by multidrug resistance bacteria, especially carbapenem-resistant Klebsiella pneumoniae (CRKP). However, fosfomycin resistant cases has been reported gradually. In this study, we reported the fosfomycin-resistant rate in CRKP strains and further revealed the molecular mechanisms in resistance gene dissemination. RESULTS: A total of 294 non-duplicated CRKP strains were collected. And 55 fosfomyin-resistant strains were detected, 94.5% of which were clustered to sequence type (ST) 11 by PCR followed up sequencing. PFGE further revealed two major groups and four singletons. The positive rates of genes responsible to fosfomycin and carbapenem resistance were 81.8% (fosA3), 12.7% (fosA5) and 94.5% (bla(KPC-2)), respectively. Genomic analysis confirmed insertion sequence (IS) 26 was the predominant structure surrounding fosA3. The fosA3 genes in six isolates were located on plasmids which were able to transfer to E. coli J53 recipient cells by means of conjugation. CONCLUSIONS: Although the resistant rate of CRKP to fosfomycin is relatively low in our area, considering its gene is located on transferrable plasmid and inserted in IS structure, continuous monitoring is still needed.202133838639
1670180.9997KPC-2-producing Klebsiella pneumoniae isolated from a Czech patient previously hospitalized in Greece and in vivo selection of colistin resistance. Carbapenemase-producing Gram-negative bacteria peak clinical interest due to their ability to hydrolyze most β-lactams, including carbapenems; moreover, their genes spread through bacterial populations by horizontal transfer. Bacteria with acquired carbapenemase have sporadically been reported in the Czech Republic, so far only in Enterobacteriaceae and Pseudomonas aeruginosa. In this study, we described the first finding of a KPC-2-producing strain of Klebsiella pneumoniae, which was isolated from a surgical wound swab, decubitus ulcer, and urine of a patient previously hospitalized in Greece. The patient underwent various antibiotic therapies including a colistin treatment. However, after approximately 20 days of the colistin therapy, the strain developed a high-level resistance to this drug. All the isolates were indistinguishable by pulsed field gel electrophoretic analysis and belonged to the international clone ST258, which is typical of KPC-producing K. pneumoniae isolates. The bla (KPC-2) gene was located on a Tn4401a transposon variant. The OmpK35 and OmpK36 genes analysis performed due to the high resistance level of the strains to β-lactams exhibited no changes in their sequence or in their expression when compared with carbapenem-susceptible isolates.201121818609
1852190.9997Genomic and Resistance Epidemiology of Gram-Negative Bacteria in Africa: a Systematic Review and Phylogenomic Analyses from a One Health Perspective. Antibiotic resistance (AR) remains a major threat to public and animal health globally. However, AR ramifications in developing countries are worsened by limited molecular diagnostics, expensive therapeutics, inadequate numbers of skilled clinicians and scientists, and unsanitary environments. The epidemiology of Gram-negative bacteria, their AR genes, and geographical distribution in Africa are described here. Data were extracted and analyzed from English-language articles published between 2015 and December 2019. The genomes and AR genes of the various species, obtained from the Pathosystems Resource Integration Center (PATRIC) and NCBI were analyzed phylogenetically using Randomized Axelerated Maximum Likelihood (RAxML) and annotated with Figtree. The geographic location of resistant clones/clades was mapped manually. Thirty species from 31 countries and 24 genera from 41 countries were analyzed from 146 articles and 3,028 genomes, respectively. Genes mediating resistance to β-lactams (including bla (TEM-1), bla (CTX-M), bla (NDM), bla (IMP), bla (VIM), and bla (OXA-48/181)), fluoroquinolones (oqxAB, qnrA/B/D/S, gyrA/B, and parCE mutations, etc.), aminoglycosides (including armA and rmtC/F), sulfonamides (sul1/2/3), trimethoprim (dfrA), tetracycline [tet(A/B/C/D/G/O/M/39)], colistin (mcr-1), phenicols (catA/B, cmlA), and fosfomycin (fosA) were mostly found in Enterobacter spp. and Klebsiella pneumoniae, and also in Serratia marcescens, Escherichia coli, Salmonella enterica, Pseudomonas, Acinetobacter baumannii, etc., on mostly IncF-type, IncX(3/4), ColRNAI, and IncR plasmids, within IntI1 gene cassettes, insertion sequences, and transposons. Clonal and multiclonal outbreaks and dissemination of resistance genes across species and countries and between humans, animals, plants, and the environment were observed; Escherichia coli ST103, K. pneumoniae ST101, S. enterica ST1/2, and Vibrio cholerae ST69/515 were common strains. Most pathogens were of human origin, and zoonotic transmissions were relatively limited.IMPORTANCE Antibiotic resistance (AR) is one of the major public health threats and challenges to effective containment and treatment of infectious bacterial diseases worldwide. Here, we used different methods to map out the geographical hot spots, sources, and evolutionary epidemiology of AR. Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., Neisseria meningitis/gonorrhoeae, Vibrio cholerae, Campylobacter jejuni, etc., were common pathogens shuttling AR genes in Africa. Transmission of the same clones/strains across countries and between animals, humans, plants, and the environment was observed. We recommend Enterobacter spp. or K. pneumoniae as better sentinel species for AR surveillance.202033234606