Dissemination dynamics of colistin resistance genes mcr-9 and mcr-10 across diverse Inc plasmid backbones. - Related Documents




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185301.0000Dissemination dynamics of colistin resistance genes mcr-9 and mcr-10 across diverse Inc plasmid backbones. BACKGROUND: The polymyxin antibiotic colistin is used as a final line of treatment for life threatening infections caused by multidrug resistant and carbapenem-resistant Gram-negative bacteria. Mobile colistin resistance genes mcr-9 and mcr-10 are increasingly detected in Enterobacteriaceae but their epidemiology is poorly understood. METHODS: The genetic characteristics of mcr-9 and mcr-10, being the only mobile colistin resistance genes detected in a local population of Enterobacter species isolated from bloodstream infections in Dartmouth Hitchcock Medical Center, USA, were elucidated and contextualized against a global dataset of mcr-9/10-bearing plasmids using genomic and phylogenetic tools. RESULTS: Seven out of 59 Enterobacter isolates carry either an mcr-9 or mcr-10 on a plasmid with distinct single and multiple replicon configurations, including IncFIB(pECLA), IncFIB(K), IncFIA(HI1)-IncFIB(K), IncFIB(pECLA)--IncFII(pECLA) and IncFIB(K)--IncFII(pECLA), whereas two genomes harbor mcr-9 on their chromosome. Global contextualization reveals that allelic variants of mcr-9 and mcr-10 are widely disseminated across diverse Inc-type plasmids, transcending geographic and taxonomic boundaries. Plasmid-borne genes conferring resistance to other antimicrobial agents, such as aminoglycoside, tetracycline and trimethoprim, tend to co-occur with mcr-9.1 and mcr-9.2 alleles. CONCLUSIONS: Findings from this study enhance our understanding of the plasmid backgrounds of mcr-9 and mcr-10, their associated antimicrobial resistance gene carriage and co-occurrence. This knowledge may be critical to inform scalable and effective public health interventions aimed at preserving the efficacy of colistin.202540999001
152610.9998Carbapenem resistance determinants and their transmissibility among clinically isolated Enterobacterales in Lebanon. BACKGROUND: The occurrence of carbapenem-resistant bacterial infections has increased significantly over the years with Gram-negative bacteria exhibiting the broadest resistance range. In this study we aimed to investigate the genomic characteristics of clinical carbapenem-resistant Enterobacterales (CRE). METHODS: Seventeen representative multi-drug resistant (MDR) isolates from a hospital setting showing high level of resistance to carbapenems (ertapenem, meropenem and imipenem) were chosen for further characterization through whole-genome sequencing. Resistance mechanisms and transferability of plasmids carrying carbapenemase-encoding genes were also determined in silico and through conjugative mating assays. RESULTS: We detected 18 different β-lactamases, including four carbapenemases (bla(NDM-1), bla(NDM-5), bla(NDM-7), bla(OXA-48)) on plasmids with different Inc groups. The combined results from PBRT and in silico replicon typing revealed 20 different replicons linked to plasmids ranging in size between 80 and 200 kb. The most prevalent Inc groups were IncFIB(K) and IncM. OXA-48, detected on 76-kb IncM1 conjugable plasmid, was the most common carbapenemase. We also detected other conjugative plasmids with different carbapenemases confirming the role of horizontal gene transfer in the dissemination of antimicrobial resistance genes. CONCLUSION: Our findings verified the continuing spread of carbapenemases in Enterobacterales and revealed the types of mobile elements circulating in a hospital setting and contributing to the spread of resistance determinants. The occurrence and transmission of plasmids carrying carbapenemase-encoding genes call for strengthening active surveillance and prevention efforts to control antimicrobial resistance dissemination in healthcare settings.202337871361
168920.9998Occurrence 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
183230.9998Long-read sequencing reveals genomic diversity and associated plasmid movement of carbapenemase-producing bacteria in a UK hospital over 6 years. Healthcare-associated infections (HCAIs) affect the most vulnerable people in society and are increasingly difficult to treat in the face of mounting antimicrobial resistance (AMR). Routine surveillance represents an effective way of understanding the circulation and burden of bacterial resistance and transmission in hospital settings. Here, we used whole-genome sequencing (WGS) to retrospectively analyse carbapenemase-producing Gram-negative bacteria from a single hospital in the UK over 6 years (n=165). We found that the vast majority of isolates were either hospital-onset (HAI) or HCAI. Most carbapenemase-producing organisms were carriage isolates, with 71 % isolated from screening (rectal) swabs. Using WGS, we identified 15 species, the most common being Escherichia coli and Klebsiella pneumoniae. Only one significant clonal outbreak occurred during the study period and involved a sequence type (ST)78 K. pneumoniae carrying bla (NDM-1) on an IncFIB/IncHI1B plasmid. Contextualization with public data revealed little evidence of this ST outside of the study hospital, warranting ongoing surveillance. Carbapenemase genes were found on plasmids in 86 % of isolates, the most common types being bla (NDM)- and bla (OXA)-type alleles. Using long-read sequencing, we determined that approximately 30 % of isolates with carbapenemase genes on plasmids had acquired them via horizontal transmission. Overall, a national framework to collate more contextual genomic data, particularly for plasmids and resistant bacteria in the community, is needed to better understand how carbapenemase genes are transmitted in the UK.202337405394
185440.9998Whole genome analysis reveals the distribution and diversity of plasmid reservoirs of NDM and MCR in commercial chicken farms in China. The increase in multidrug-resistant (MDR) Enterobacteriaceae presents a significant challenge to clinical treatment, particularly in infections where carbapenems and colistin serve as the last-resort antimicrobial agents. In this study, we isolated 119 non-repetitive gram-negative bacteria from MacConkey medium supplemented with imipenem and colistin. The isolates were dominated by Klebsiella pneumoniae (58.0%, n = 69) and Escherichia coli (31.1%, n = 37). The predominant sequence types (STs) of E. coli were ST226, ST1286, and ST11738, whereas K. pneumoniae displayed ST152, ST395, and ST709 as major types. Genomic analysis identified mcr-1/3/8/9 in 44 strains and bla(NDM) in 63 strains across various species. IncX3 (n = 57) and IncFII (n = 5) were the most common bla(NDM-5)-carrying plasmid types. Several plasmid replicons were associated with mcr genes, including IncI2, IncX4, and novel plasmids. Remarkably, we discovered four combinations of bla(NDM) and mcr co-occurrence in 28 isolates, including bla(NDM-5)/mcr-1, bla(NDM-5)/mcr-3, bla(NDM-5)/mcr-8, and bla(NDM-5)/mcr-9. Our findings reveal that chicken farms are significant reservoirs for both bla(NDM) and mcr genes, with frequent co-occurrence of these resistance determinants. The presence of these genes alongside other resistance factors, such as blaESBL, highlights a critical public health risk. This study underscores the need for enhanced surveillance and intervention strategies to mitigate the spread of MDR pathogens from agricultural environments to clinical settings.IMPORTANCEThis study reveals that commercial poultry farms in China serve as critical reservoirs for MDR gram-negative bacteria harboring carbapenemase (bla(NDM)) and mobilized colistin resistance (mcr) genes. By analyzing 119 isolates, we uncovered extensive genetic diversity and plasmid-mediated co-occurrence of these resistance determinants, enabling bacteria to evade nearly all available treatments. Alarmingly, the horizontal transfer of resistance genes via highly mobile plasmids facilitates their spread across microbial communities and potentially into clinical settings. These findings underscore the urgent need to address antibiotic overuse in agriculture and strengthen surveillance under the One Health framework. The persistence of MDR pathogens in poultry environments highlights a significant risk for zoonotic transmission, emphasizing the necessity of coordinated interventions to curb the global antimicrobial resistance crisis.202540488461
184250.9998Emergence 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
189760.9997Plasmid-based replicon typing: Useful tool in demonstrating the silent pandemic of plasmid-mediated multi-drug resistance in Enterobacterales. BACKGROUND: Multi-drug resistant Enterobacterales increasingly isolated in hospital settings have a significant impact on therapy and overall treatment costs. Conjugative plasmids carrying relevant resistance genes have been described as the most frequent mechanism of acquisition and spread of resistance. PCR-based replicon typing (PBRT) is a method for plasmid identification and incompatibility typing which helps detect the presence of plasmid families in these bacteria. This study was undertaken to provide an insight into the prevalence of resistance plasmids in MDR Enterobacterales in our tertiary care setting. METHODS: A selection of one hundred multi-drug resistant Enterobacterale isolates sourced from clinical samples were subjected to PCR-based replicon typing. RESULTS: A total of 21 plasmid replicon types were detected from 85% of the isolates out of the 28 families described in literature. Majority of the isolates (54%) showed three or more replicons. IncF was the most frequent plasmid family detected with FIA being the most common replicon type (43%) followed by FII (29%) and FIB (28%) replicons. Among the IncX plasmid family, X3 replicon was the commonest (14%). IncF and IncX plasmid families are known to carry a large spectrum of resistance genes. CONCLUSION: The presence of these plasmids engenders emergent steps to be taken for prevention of their transmission in the form of strict infection control measures in the hospital and adoption of novel methods of plasmid curing to eliminate the plasmids from these organisms rendering them susceptible to the currently used antimicrobials.202540463599
189670.9997Difference analysis and characteristics of incompatibility group plasmid replicons in gram-negative bacteria with different antimicrobial phenotypes in Henan, China. BACKGROUND: Multi-drug-resistant organisms (MDROs) in gram-negative bacteria have caused a global epidemic, especially the bacterial resistance to carbapenem agents. Plasmid is the common vehicle for carrying antimicrobial resistance genes (ARGs), and the transmission of plasmids is also one of the important reasons for the emergence of MDROs. Different incompatibility group plasmid replicons are highly correlated with the acquisition, dissemination, and evolution of resistance genes. Based on this, the study aims to identify relevant characteristics of various plasmids and provide a theoretical foundation for clinical anti-infection treatment. METHODS: 330 gram-negative strains with different antimicrobial phenotypes from a tertiary hospital in Henan Province were included in this study to clarify the difference in incompatibility group plasmid replicons. Additionally, we combined the information from the PLSDB database to elaborate on the potential association between different plasmid replicons and ARGs. The VITEK mass spectrometer was used for species identification, and the VITEK-compact 2 automatic microbial system was used for the antimicrobial susceptibility test (AST). PCR-based replicon typing (PBRT) detected the plasmid profiles, and thirty-three different plasmid replicons were determined. All the carbapenem-resistant organisms (CROs) were tested for the carbapenemase genes. RESULTS: 21 plasmid replicon types were detected in this experiment, with the highest prevalence of IncFII, IncFIB, IncR, and IncFIA. Notably, the detection rate of IncX3 plasmids in CROs is higher, which is different in strains with other antimicrobial phenotypes. The number of plasmid replicons they carried increased with the strain resistance increase. Enterobacterales took a higher number of plasmid replicons than other gram-negative bacteria. The same strain tends to have more than one plasmid replicon type. IncF-type plasmids tend to be associated with MDROs. Combined with PLSDB database analysis, IncFII and IncX3 are critical platforms for taking bla(KPC-2) and bla(NDM). CONCLUSIONS: MDROs tend to carry more complex plasmid replicons compared with non-MDROs. The plasmid replicons that are predominantly prevalent and associated with ARGs differ in various species. The wide distribution of IncF-type plasmids and their close association with MDROs should deserve our attention. Further investigation into the critical role of plasmids in the carriage, evolution, and transmission of ARGs is needed.202438373913
168680.9997Resistome 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
190290.9997Large-scale analysis of putative plasmids in clinical multidrug-resistant Escherichia coli isolates from Vietnamese patients. INTRODUCTION: In the past decades, extended-spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant (CR) Escherichia coli isolates have been detected in Vietnamese hospitals. The transfer of antimicrobial resistance (AMR) genes carried on plasmids is mainly responsible for the emergence of multidrug-resistant E. coli strains and the spread of AMR genes through horizontal gene transfer. Therefore, it is important to thoroughly study the characteristics of AMR gene-harboring plasmids in clinical multidrug-resistant bacterial isolates. METHODS: The profiles of plasmid assemblies were determined by analyzing previously published whole-genome sequencing data of 751 multidrug-resistant E. coli isolates from Vietnamese hospitals in order to identify the risk of AMR gene horizontal transfer and dissemination. RESULTS: The number of putative plasmids in isolates was independent of the sequencing coverage. These putative plasmids originated from various bacterial species, but mostly from the Escherichia genus, particularly E. coli species. Many different AMR genes were detected in plasmid contigs of the studied isolates, and their number was higher in CR isolates than in ESBL-producing isolates. Similarly, the bla(KPC-2), bla(NDM-5), bla(OXA-1), bla(OXA-48), and bla(OXA-181) β-lactamase genes, associated with resistance to carbapenems, were more frequent in CR strains. Sequence similarity network and genome annotation analyses revealed high conservation of the β-lactamase gene clusters in plasmid contigs that carried the same AMR genes. DISCUSSION: Our study provides evidence of horizontal gene transfer in multidrug-resistant E. coli isolates via conjugative plasmids, thus rapidly accelerating the emergence of resistant bacteria. Besides reducing antibiotic misuse, prevention of plasmid transmission also is essential to limit antibiotic resistance.202337323902
1858100.9997Molecular Characteristics of Antimicrobial Resistance and Virulence in Klebsiella pneumoniae Strains Isolated from Goose Farms in Hainan, China. We retrospectively investigated 326 samples that were collected from goose farms in Hainan Province, China, in 2017. A total of 33 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates were identified from 326 samples, and the 33 CRKP isolates were characterized based on whole-genome sequencing (WGS) data from the Illumina and Oxford Nanopore Technologies (ONT) platforms. All of these 33 CRKP isolates possessed bla(NDM-5), and a single isolate coharbored mcr-1 and bla(NDM-5), while 4 isolates carried multiple virulence and metal tolerance gene clusters. One CRKP strain (CMG-35-2) was selected for long sequence reading. A hybrid plasmid carrying the virulence, resistance, and metal resistance gene in the strain was found. It possessed 2 backbones [IncFIB(K)-IncFII(K)] within a single plasmid that were closely related to K. pneumoniae plasmids from a human-associated habitat in the United States and from a human isolate in Hong Kong. A mouse abdominal infection model indicated that that strain was of the moderate virulence phenotype. This study revealed that K. pneumoniae on goose farms is an important reservoir for bla(NDM-5) and these bacteria are represented by a diversity of sequence types. The heterozygous multiple drug resistance genes carried on plasmids highlighted the genetic complexity of CRKP and the urgent need for continued active surveillance. IMPORTANCE CRKP is one of the most important pathogens, which can cause infection not only in humans but also in waterfowl. The discovery of bla(NDM-5)-producing K. pneumoniae in waterfowl farms in recent years suggests that waterfowl are an important reservoir for bla(NDM-5)-producing Enterobacteriaceae. However, there are few studies on the spread of bla(NDM-5)-producing bacteria in waterfowl farms. Our study showed that the IncX3 plasmid carrying bla(NDM-5) in goose farms is widely present in K. pneumoniae isolates and a large number of resistance genes are accumulated in it. We found a transferable IncFIB-FII hybrid plasmid that combines virulence, resistance, and metal resistance genes, which allow transfer of these traits between bacteria in different regions. The results of this study contribute to a better understanding of the prevalence and transmission of carbapenem-resistant K. pneumoniae in goose farms.202235389252
1667110.9997Colistin 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
1877120.9997Prevalence and Traits of Mobile Colistin Resistance Gene Harbouring Isolates from Different Ecosystems in Africa. The mobile colistin resistance (mcr) gene threatens the efficacy of colistin (COL), a last-line antibiotic used in treating deadly infections. For more than six decades, COL is used in livestock around the globe, including Africa. The use of critically important antimicrobial agents, like COL, is largely unregulated in Africa, and many other factors militate against effective antimicrobial stewardship in the continent. Currently, ten mcr genes (mcr-1 to mcr-10) have been described. In Africa, mcr-1, mcr-2, mcr-3, mcr-5, mcr-8, and mcr-9 have been detected in isolates from humans, animals, foods of animal origin, and the environment. These genes are harboured by Escherichia coli, Klebsiella, Salmonella, Citrobacter, Enterobacter, Pseudomonas, Aeromonas, Alcaligenes, and Acinetobacter baumannii isolates. Different conjugative and nonconjugative plasmids form the backbone for mcr in these isolates; however, mcr-1 and mcr-3 have also been integrated into the chromosome of some African strains. Insertion sequences (ISs) (especially ISApl1), either located upstream or downstream of mcr, class 1 integrons, and transposons, are drivers of mcr in Africa. Genes coding multi/extensive drug resistance and virulence are colocated with mcr on plasmids in African strains. Transmission of mcr to/among African strains is nonclonal. Contact with mcr-habouring reservoirs, the consumption of contaminated foods of animal/plant origin or fluid, animal-/plant-based food trade and travel serve as exportation, importation, and transmission routes of mcr gene-containing bacteria in Africa. Herein, the current status of plasmid-mediated COL resistance in humans, food-producing animals, foods of animal origin, and environment in Africa is discussed.202133553426
1527130.9997Emergence of an Escherichia coli strain co-harbouring mcr-1 and bla(NDM-9) from a urinary tract infection in Taiwan. OBJECTIVES: Multidrug-resistant bacteria have become a serious threat worldwide. In particular, the coexistence of carbapenemase genes and mcr-1 leaves few available treatment options. Here we report a multidrug-resistant Escherichia coli isolate harbouring both mcr-1 and bla(NDM-9) from a patient with a urinary tract infection. METHODS: Antimicrobial susceptibility and resistance genes of the E. coli isolate were characterised. Furthermore, the assembled genome sequences of mcr-1- and bla(NDM-9)-carrying plasmids were determined and comparative genetic analysis with closely related plasmids was carried out. RESULTS: Three contigs were assembled comprising the E. coli chromosome and two plasmids harbouring mcr-1 (p5CRE51-MCR-1) and bla(NDM-9) (p5CRE51-NDM-9), respectively. Whole-genome sequencing revealed that the two antimicrobial resistance genes are located on individual plasmids. CONCLUSIONS: The emergence of coexistence of carbapenemase genes and mcr-1 in Enterobacteriaceae highlights a serious threat to antimicrobial therapy.201930312830
1524140.9997Characterization of a Novel mcr-8.2-Bearing Plasmid in ST395 Klebsiella pneumoniae of Chicken Origin. The emergence of mobile colistin resistance mcr genes undermines the efficacy of colistin as the last-resort drug for multi-drug resistance infections and constitutes a great public health concern. Plasmids play a critical role in the transmission of mcr genes among bacteria. One colistin-resistant Klebsiella pneumoniae strain of chicken origin was collected and analyzed by antimicrobial susceptibility testing, PCR, conjugation assay and S1-PFGE. Whole-genome sequencing (WGS) approach combining Illumina and MinION platforms was utilized to decipher the underlying colistin resistance mechanism and genetic context. A novel mcr-8.2-bearing plasmid p2019036D-mcr8-345kb with 345 655 bp in size encoding various resistance genes including floR, sul1, aadA16, aadA2, bla (CTX-M-27), bla (DHA-1), tet(D), dfrA12 and qnrB4 was identified responsible for the colistin resistance phenotype. Plasmid comparison has shown that the mcr-8.2-bearing plasmid differed from other reported plasmids positive for mcr-8.2 but shared the same core mcr-8.2-bearing conserved region. This study demonstrates the emergence of mcr-8.2-bearing K. pneumoniae of animal origin is a potential risk to humans.202032606828
1637150.9997Genomic surveillance of antimicrobial resistance in bovine fecal samples from Lebanon. Antimicrobial resistance (AMR) threatens human and animal health worldwide, driven by the spread of extended-spectrum β-lactamase (ESBL)-producing, and carbapenem-resistant Gram-negative bacteria. In Lebanon, inadequate surveillance and antibiotic misuse worsen the issue. Animal fecal material is an important reservoir of resistance genes and mobile elements. This study aims to address AMR in bovine feces. To achieve this, bovine fecal samples were collected from 24 farms in Lebanon. Sixty-two ESBL-producing bacteria were recovered on CHROMagar ESBL and whole-genome sequencing followed by in silico typing was used to determine the resistance genes, virulence factors, and mobile genetic elements. Disk diffusion assay revealed the prevalence of multidrug-resistant (MDR) Gram-negative bacteria (33/62) with Escherichia coli being the most common (37/62). Resistance to amoxicillin, ceftriaxone, and cefotaxime was detected in all 37 E. coli isolates, with one also exhibiting resistance to colistin. β-lactam resistance was primarily associated with bla(CTX-M-15) and bla(TEM-1B), while colistin resistance was linked to mcr-1.1 on an IncHI2A/IncFIC multi-replicon plasmid. Plasmid typing identified 22 replicons, the most common being IncFIB and IncFII. Virulence factor analysis identified enterotoxin-encoding genes in one E. coli isolate, suggesting a potentially pathogenic strain with diarrheagenic properties among the recovered isolates. The findings of this study revealed highly resistant Gram-negative bacteria with plasmid-mediated resistance to critical antibiotics such as colistin, emphasizing the risks posed to human and livestock health. Comprehensive surveillance and responsible antibiotic use, guided by an integrated One Health approach, are essential steps to effectively tackle the interconnected challenges of AMR.202540482361
1732160.9997High Carriage Rate of the Multiple Resistant Plasmids Harboring Quinolone Resistance Genes in Enterobacter spp. Isolated from Healthy Individuals. Antimicrobial-resistant bacteria causing intractable and even fatal infections are a major health concern. Resistant bacteria residing in the intestinal tract of healthy individuals present a silent threat because of frequent transmission via conjugation and transposition. Plasmids harboring quinolone resistance genes are increasingly detected in clinical isolates worldwide. Here, we investigated the molecular epidemiology of plasmid-mediated quinolone resistance (PMQR) in Gram-negative bacteria from healthy service trade workers. From 157 rectal swab samples, 125 ciprofloxacin-resistant strains, including 112 Escherichia coli, 10 Klebsiella pneumoniae, two Proteus mirabilis, and one Citrobacter braakii, were isolated. Multiplex PCR screening identified 39 strains harboring the PMQR genes (including 17 qnr,19 aac(6')-Ib-cr, and 22 oqxA/oqxB). The genome and plasmid sequences of 39 and 31 strains, respectively, were obtained by short- and long-read sequencing. PMQR genes mainly resided in the IncFIB, IncFII, and IncR plasmids, and coexisted with 3-11 other resistance genes. The high PMQR gene carriage rate among Gram-negative bacteria isolated from healthy individuals suggests the high-frequency transmission of these genes via plasmids, along with other resistance genes. Thus, healthy individuals may spread antibiotic-resistant bacterial, highlighting the need for improved monitoring and control of the spread of antibiotic-resistant bacteria and genes in healthy individuals.202135052892
1525170.9997Genetic Characterization of Enterobacter hormaechei Co-Harboring bla (NDM-1) and mcr-9 Causing Upper Respiratory Tract Infection. PURPOSE: With the spread of multiple drug-resistant bacteria, bla (NDM-1) and mcr-9 have been detected in various bacteria worldwide. However, the simultaneous detection of bla (NDM-1) and mcr-9 in Enterobacter hormaechei has been rarely reported. This study identified an E. hormaechei strain carrying both bla (NDM-1) and mcr-9. We investigated the genetic characteristics of these two resistance genes in detail, elucidating various potential mechanisms by which they may be transmitted. METHODS: Bacterial genomic features and possible origins were assessed by whole-genome sequencing (WGS) with Illumina and PacBio platforms and phylogenetic analysis. Subsequent investigations were performed, including antimicrobial susceptibility testing and multilocus sequence typing (MLST). RESULTS: We isolated an E. hormaechei strain DY1901 carrying both bla (NDM-1) and mcr-9 from the sputum sample. Susceptibility testing showed that the isolate was multidrug-resistant. Multiple antibiotic resistance genes and virulence genes are widely distributed in DY1901. S1-PFGE, Southern blotting, and plasmid replicon typing showed that DY1901 carried four plasmids. The plasmid carrying mcr-9 was 259Kb in size and belonged to IncHI2, while the plasmid carrying bla (NDM-1) was 45Kb in length and belonged to IncX3. CONCLUSION: The E. hormaechei strain isolated in this study has a broad antibiotic resistance spectrum, posing a challenge to clinical treatment. Plasmids carrying mcr-9 are fusion plasmids, and those taking NDM are widely disseminated in China, suggesting that we should conduct routine genomic surveillance on such plasmids to curb the spread of drug-resistant bacteria in the region.202236068833
1727180.9997Coexistence and genomics characterization of mcr-1 and extended-spectrum-β-lactamase-producing Escherichia coli, an emerging extensively drug-resistant bacteria from sheep in China. The emergence of pathogens harboring multiple resistance genes poses a great threat to global public health. However, the coexistence of mobile resistance genes that provide resistance to both third-generation cephalosporins and colistin in sheep-origin Escherichia coli has not been previously investigated in China. This study is the first to characterize five E. coli isolates from sheep in Shaanxi province that harbor both Extended-Spectrum β-Lactamase (ESBL) and mcr-1 resistance genes. The isolates were identified and characterized by Illumina sequencing, nanopore sequencing, bioinformatic analysis, conjugation experiments, and antimicrobial susceptibility testing. Genetic analysis revealed that bla(CTX-M-55) gene, mediated by the IS26, was located on the IncFIB-IncFIC plasmid, while the mcr-1 gene was located on the IncI2(Delta) plasmid. Notably, two copies of bla(CTX-M-55) gene were also identified on the chromosome of one isolate (SX45), facilitated by the ISEcp1 insertion sequence. Additionally, the plasmid pSX23-2 was identified as a complex plasmid derived through homologous recombination of pMG337 from E. coli (MK878890) and pZY-1 from Citrobacter freundii (CP055248). Data mining of publicly available databases revealed that isolates carrying both bla(CTX-M-55) and mcr-1 genes have been found in humans, animals, and the environment, indicating the widespread presence of these critical resistance genes across different niches. Antimicrobial susceptibility testing showed that the five isolates were resistant to a nearly all tested antibiotics, except meropenem. Conjugative transfer experiments demonstrated that the IncFIB-IncFIC and IncI2(Delta) plasmids carrying mcr-1 and bla(CTX-M-55) were capable of transferring between different sequence types (STs) of sheep-origin E. coli, including ST10, ST162, and ST457. This finding suggests the potential for wide dissemination of these resistance markers among diverse E. coli strains. Overall, the characterization of these ESBL and mcr-1 co-harboring isolates enhances our understanding of the spread of these resistance genes in sheep-origin E. coli. Global surveillance of these isolates, particularly within the One Health framework, is essential to monitor and mitigate the risks posed by the dissemination of these resistance genes across various settings.202439426540
1868190.9997Genomic Characterization of Carbapenem-Resistant Klebsiella pneumoniae ST1440 and Serratia marcescens Isolates from a COVID-19 ICU Outbreak in Ecuador. The global rise of antimicrobial resistance (AMR), exacerbated by the COVID-19 pandemic, has led to a surge in infections caused by multidrug-resistant (MDR) bacteria. A key driver of this phenomenon is co-selection, where exposure to one antimicrobial promotes resistance to others via horizontal gene transfer (HGT) mediated by mobile genetic elements (MGEs). Carbapenem-resistant Enterobacteriaceae, known for their genomic plasticity, are particularly worrisome; yet genomic data from Latin America-especially Ecuador-remain scarce. This study investigated four carbapenem-resistant clinical isolates (two Klebsiella pneumoniae ST1440 and two Serratia marcescens) from tracheal aspirates of three ICU patients during a COVID-19 outbreak at Hospital IESS Quito Sur, Ecuador. Phenotypic profiling and whole-genome sequencing were performed, followed by bioinformatic reconstruction of plasmid content. Nineteen plasmids were identified, carrying 70 resistance-related genes, including antimicrobial resistance genes (ARGs), metal resistance genes (MRGs), integrons, transposons, and insertion sequences. Hierarchical clustering revealed six distinct gene clusters, with several co-localizing ARGs and genes for resistance to disinfectants and heavy metals-suggesting strong co-selective pressure. Conjugative plasmids harboring high-risk elements such as blaKPC-2, qacE, and Tn4401 were found in multiple isolates, indicating potential interspecies dissemination. These findings emphasize the importance of plasmid-mediated resistance during the pandemic and highlight the urgent need to enhance genomic surveillance and infection control, particularly in resource-limited healthcare settings.202541156746