Phylogeographical Landscape of Citrobacter portucalensis Carrying Clinically Relevant Resistomes. - Related Documents




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187101.0000Phylogeographical Landscape of Citrobacter portucalensis Carrying Clinically Relevant Resistomes. During a surveillance study conducted to assess the occurrence and genomic landscape of critical priority pathogens circulating at the human-animal-environment interface in Brazil, as part of the Grand Challenges Explorations-New Approaches to Characterize the Global Burden of Antimicrobial Resistance program, two multidrug-resistant (MDR) Citrobacter portucalensis carrying bla(CTX-M-15) extended-spectrum β-lactamase (ESBL) genes, isolated from green sea turtles, were characterized. Genomic and phylogeographical analysis of C. portucalensis genomes available in public databases revealed the intercontinental dissemination of clades carrying different arrays of clinically relevant genes conferring resistance to carbapenems, broad-spectrum cephalosporins, cephamycins, aminoglycosides and fluoroquinolones, disinfectants, and heavy metals. Our observations suggest that C. portucalensis could be emerging as critical priority bacteria of both public and One Health importance worldwide. IMPORTANCE The global spread of antibiotic-resistant priority pathogens beyond the hospital setting is a critical issue within a One Health context that integrates the human-animal-environment interfaces. On the other hand, next-generation sequencing technologies along with user-friendly and high-quality bioinformatics tools have improved the identification of bacterial species, and bacterial resistance surveillance. The novel Citrobacter portucalensis species was proposed in 2017 after taxonomic reclassification and definition of the strain A60(T) isolated in 2008. Here, we presented genomic data showing the occurrence of multidrug-resistant C. portucalensis isolates carrying bla(CTX-M-15) ESBL genes in South America. Additionally, we observed the intercontinental dissemination of clades harboring a broad resistome to clinically relevant antibiotics. Therefore, these findings highlight that C. portucalensis is a global MDR bacteria that carries intrinsic bla(CMY)- and qnrB-type genes and has become a critical priority pathogen due to the acquisition of clinically relevant resistance determinants, such as ESBL and carbapenemase-encoding genes.202235357225
186510.9998Characterization of mobile resistance elements in extended-spectrum β-lactamase producing gram-negative bacteria from aquatic environment. Extended-spectrum β-lactamase producing (ESBL) bacteria from aquatic environments can pose potential threats to public health due to their capability of spreading antimicrobial resistance (AMR) genes through mobile genetic elements (MGEs), such as plasmids, insertion sequences (ISs), transposons, and integrons. Currently, there is no policy for routine monitoring of AMR genes in aquatic environments and their roles in transmission are therefore unknown. Previous metagenomic and PCR-based culture-independent approaches are limited in recovering AMR resistant aquatic bacteria isolates and the data resolution generated are not able to provide detailed genetic comparison with known human pathogens particularly for determining genetic islands harbouring AMR genes. To address these gaps, we thus investigated the genetic profiles of ESBL-producing gram-negative aquatic bacteria found from water body sites within Singapore, examining the AMR genes carried and their associated MGEs. In total, 16 ESBL-producing gram-negative bacteria were identified, of which 8 were Escherichia coli, 3 Klebsiella pneumoniae, and 5 Aeromonas spp. Whole genome sequencing (WGS) analysis revealed the presence of 12 distinct classes of AMR genes, including 16 distinct variants of β-lactamase, of which bla(CTX-M) was the dominant beta-lactamase genotype in all 11 Enterobacterales. The AMR genetic islands in the aquatic bacteria were also found to share similar genetic structures similar to those of circulating ESBL bacteria causing human infections. These findings underscore the potential role of aquatic ESBL bacteria as AMR reservoirs for human pathogens, suggesting that aquatic bacteria may facilitate the hidden transmission of AMR mediated by MGEs through horizontal gene transfer across different sources and species, highlighting the importance of integrating environmental AMR monitoring into local surveillance strategies.202540245502
572420.9998Convergence of virulence and resistance in international clones of WHO critical priority enterobacterales isolated from Marine Bivalves. The global spread of critical-priority antimicrobial-resistant Enterobacterales by food is a public health problem. Wild-caught seafood are broadly consumed worldwide, but exposure to land-based pollution can favor their contamination by clinically relevant antimicrobial-resistant bacteria. As part of the Grand Challenges Explorations: New Approaches to Characterize the Global Burden of Antimicrobial Resistance Program, we performed genomic surveillance and cell culture-based virulence investigation of WHO critical priority Enterobacterales isolated from marine bivalves collected in the Atlantic Coast of South America. Broad-spectrum cephalosporin-resistant Klebsiella pneumoniae and Escherichia coli isolates were recovered from eight distinct geographical locations. These strains harbored bla(CTX-M)-type or bla(CMY)-type genes. Most of the surveyed genomes confirmed the convergence of wide virulome and resistome (i.e., antimicrobials, heavy metals, biocides, and pesticides resistance). We identified strains belonging to the international high-risk clones K. pneumoniae ST307 and E. coli ST131 carrying important virulence genes, whereas in vitro experiments confirmed the high virulence potential of these strains. Thermolabile and thermostable toxins were identified in some strains, and all of them were biofilm producers. These data point to an alarming presence of resistance and virulence genes in marine environments, which may favor horizontal gene transfer and the spread of these traits to other bacterial species.202235383231
186730.9997Plasmid diversity of Serratia marcescens and Klebsiella pneumoniae isolates involved in two carbapenem-resistant Enterobacteriaceae outbreaks in a Swiss hospital. This study investigates two distinct carbapenemase-producing Enterobacteriaceae outbreaks involving patients and contaminated sink traps at the University Hospital of Lausanne. It focuses on the diversity and transmission dynamics of plasmids carrying carbapenemase genes. Between 2022 and 2023, 57 carbapenem-resistant Klebsiella pneumoniae and Serratia marcescens isolates were collected and analyzed. Core-genome MLST confirmed genetic similarity among isolates, linking the outbreaks to sink trap contamination. DNA extraction, sequencing (MinION/Illumina MiSeq), and assembly were performed, followed by ARG screening and plasmid typing. Plasmids were annotated, clustered, and compared using core SNP distances and structural analyses. Known plasmids were identified through PLSDB database matching. Eight MLST types were identified in K. pneumoniae and one (ST356) in S. marcescens. Analysis of 52 bla-carrying plasmids revealed 22 plasmid clusters, including 6 bla(NDM-1) clusters in K. pneumoniae and 4 bla(KPC-2) clusters in S. marcescens. Plasmids showed close relatedness within and across patient and environmental isolates, with core SNP distances ranging from 0 to 18. Some bla(NDM-1) plasmids in K. pneumoniae clustered tightly, suggesting persistence and potential cross-contamination routes. The findings highlight sink traps as critical reservoirs for carbapenem-resistant Enterobacteriaceae and plasmids, promoting resistance gene spread across species. The observed plasmid diversity indicates transmission can occur independently of bacterial clonal spread, challenging traditional outbreak definitions. IMPORTANCE: This research is critical in addressing the growing threat of antibiotic resistance, driven by the spread of resistance genes through plasmids. Plasmids, which can transfer between different bacteria, play a major role in spreading multidrug resistance, posing a serious challenge to healthcare systems worldwide. By highlighting how plasmids can move independently of bacterial spread, this study reveals the complexity of resistance transmission. It also underscores the importance of environmental reservoirs, such as hospital sink traps, in harboring and spreading resistant bacteria. These findings emphasize the need for better monitoring of plasmids and targeted infection control measures to prevent the spread of resistance genes and protect the effectiveness of current antibiotics.202540396774
186640.9997Drivers of the emergence and dissemination of high-risk resistance genes in cattle farm. Extended spectrum β-lactamase (ESBL)- and carbapenemase-producing Enterobacterales (CPE) are recognized by WHO as critical concerns. The high cephalosporin resistance rate in a cattle farm in 2018 prompted us to conduct long-term (2019-2023) and extensive monitoring to explore risk factors for the import and transmission of ESBLs and CPE in this farm. Among 1288 samples from cattle, the environment, milk, and biological vectors, 48.8 % carried bla(CTX-M)-positive Enterobacterales with bla(CTX-M-55) being dominant (76.4 %), and bla(NDM-5)-positive strains emerged in 2022 with a 1.9 % detection rate. bla(CTX-M-55) and bla(NDM-5) were likely introduced through various routes, especially wild birds, and have persisted due to overuse of cephalosporins in the farm. The spread of these genes was driven by the horizontal transmission of IncHI2 and IncX3 plasmids and clonal dissemination of certain clones. Cross-regional and cross-border transmission of bla(CTX-M-55)- and/or bla(NDM-5)-bearing bacteria and plasmids possibly occurred via wild birds, animal trade, and other means. Our findings suggest that the import, persistence, and dissemination of these genes within and beyond this farm, were fueled by suboptimal biosecurity practices and inadequate antibiotic stewardship, highlighting the urgency for integrated public and ecosystem health policies to prevent the spread of resistance genes as part of a holistic One Health strategy. ENVIRONMENTAL IMPLICATION: The high prevalence and long-term persistence of extended-spectrum β-lactamases and the emergence of carbapenemases in cattle and the environment signify a critical risk of transmitting high-risk resistance genes, posing a significant threat to human health. Consequently, bacteria carrying these genes in animal farms should be regarded as "hazardous materials". Import, persistence, and dissemination of these genes within and beyond this farm were exacerbated by suboptimal biosecurity practices and inadequate antibiotic stewardship, highlighting the urgency for integrated public and ecosystem health policies to mitigate the environmental risks associated with gene transmission as part of a comprehensive One Health strategy.202539899930
187050.9997Novel Insights into bla(GES) Mobilome Reveal Extensive Genetic Variation in Hospital Effluents. Mobile genetic elements contribute to the emergence and spread of multidrug-resistant bacteria by enabling the horizontal transfer of acquired antibiotic resistance among different bacterial species and genera. This study characterizes the genetic backbone of bla(GES) in Aeromonas spp. and Klebsiella spp. isolated from untreated hospital effluents. Plasmids ranging in size from 9 to 244 kb, sequenced using Illumina and Nanopore platforms, revealed representatives of plasmid incompatibility groups IncP6, IncQ1, IncL/M1, IncFII, and IncFII-FIA. Different GES enzymes (GES-1, GES-7, and GES-16) were located in novel class 1 integrons in Aeromonas spp. and GES-5 in previously reported class 1 integrons in Klebsiella spp. Furthermore, in Klebsiella quasipneumoniae, bla(GES-5) was found in tandem as a coding sequence that disrupted the 3' conserved segment (CS). In Klebsiella grimontii, bla(GES-5) was observed in two different plasmids, and one of them carried multiple IncF replicons. Three Aeromonas caviae isolates presented bla(GES-1), one Aeromonas veronii isolate presented bla(GES-7), and another A. veronii isolate presented bla(GES-16). Multilocus sequence typing (MLST) analysis revealed novel sequence types for Aeromonas and Klebsiella species. The current findings highlight the large genetic diversity of these species, emphasizing their great adaptability to the environment. The results also indicate a public health risk because these antimicrobial-resistant genes have the potential to reach wastewater treatment plants and larger water bodies. Considering that they are major interfaces between humans and the environment, they could spread throughout the community to clinical settings. IMPORTANCE In the "One Health" approach, which encompasses human, animal, and environmental health, emerging issues of antimicrobial resistance are associated with hospital effluents that contain clinically relevant antibiotic-resistant bacteria along with a wide range of antibiotic concentrations, and lack regulatory status for mandatory prior and effective treatment. bla(GES) genes have been reported in aquatic environments despite the low detection of these genes among clinical isolates within the studied hospitals. Carbapenemase enzymes, which are relatively unusual globally, such as GES type inserted into new integrons on plasmids, are worrisome. Notably, K. grimontii, a newly identified species, carried two plasmids with bla(GES-5), and K. quasipneumoniae carried two copies of bla(GES-5) at the same plasmid. These kinds of plasmids are primarily responsible for multidrug resistance among bacteria in both clinical and natural environments, and they harbor resistant genes against antibiotics of key importance in clinical therapy, possibly leading to a public health problem of large proportion.202235880869
187360.9997A Novel Multidrug Resistant, Non-Tn4401 Genetic Element-Bearing, Strain of Klebsiella pneumoniae Isolated From an Urban Lake With Drinking and Recreational Water Reuse. Antimicrobial resistance (AMR) is an increasing and urgent issue for human health worldwide, as it leads to the reduction of available antibiotics to treat bacterial infections, in turn increasing hospital stays and lethality. Therefore, the study and genomic surveillance of bacterial carriers of resistance in and outside of clinical settings is of utter importance. A colony of multidrug resistant (MDR) bacteria identified as Klebsiella spp., by 16S rDNA amplicon sequencing, has been isolated from an urban lake in Brazil, during a drug-degrading bacterial prospection. Genomic analyses revealed the bacteria as Klebsiella pneumoniae species. Furthermore, the in silico Multilocus Sequence Typing (MLST) identified the genome as a new sequence type, ST5236. The search for antimicrobial resistance genes (ARGs) detected the presence of genes against beta-lactams, fosfomycin, acriflavine and efflux pumps, as well as genes for heavy metal resistance. Of particular note, an extended-spectrum beta-lactamase gene (blaCTX-M-15) has been detected in close proximity to siphoviridae genes, while a carbapenemase gene (KPC-2) has been found in an extrachromosomal contig, within a novel non-Tn4401 genetic element (NTE(KPC)). An extrachromosomal contig found in the V3 isolate is identical to a contig of a K. pneumoniae isolate from a nearby hospital, which indicates a putative gene flow from the hospital network into Paranoá lake. The discovery of a MDR isolate in this lake is worrisome, as the region has recently undergone periods of water scarcity causing the lake, which receives treated wastewater effluent, and is already used for recreational purposes, to be used as an environmental buffer for drinking water reuse. Altogether, our results indicate an underrepresentation of environmental K. pneumoniae among available genomes, which may hamper the understanding of the population dynamics of the species in the environment and its consequences in the spread of ARGs and virulence genes.202134899623
187270.9997Escherichia coli ST2797 Is Abundant in Wastewater and Might Be a Novel Emerging Extended-Spectrum Beta-Lactamase E. coli. The increasing prevalence of antibiotic-resistant bacteria is an emerging threat to global health. The analysis of antibiotic-resistant enterobacteria in wastewater can indicate the prevalence and spread of certain clonal groups of multiresistant bacteria. In a previous study of Escherichia coli that were isolated from a pump station in Norway over 15 months, we found a recurring E. coli clone that was resistant to trimethoprim, ampicillin, and tetracycline in 201 of 3,123 analyzed isolates (6.1%). 11 representative isolates were subjected to whole-genome sequencing and were found to belong to the MLST ST2797 E. coli clone with plasmids carrying resistance genes, including bla(TEM-1B), sul2, dfrA7, and tetB. A phenotypic comparison of the ST2797 isolates with the uropathogenic ST131 and ST648 that were repeatedly identified in the same wastewater samples revealed that the ST2797 isolates exhibited a comparable capacity for temporal survival in wastewater, greater biofilm formation, and similar potential for the colonization of mammalian epithelial cells. ST2797 has been isolated from humans and has been found to carry extended spectrum β-lactamase (ESBL) genes in other studies, suggesting that this clonal type is an emerging ESBL E. coli. Collectively, these findings show that ST2797 was more ubiquitous in the studied wastewater than were the infamous ST131 and ST648 and that ST2797 may have similar abilities to survive in the environment and cause infections in humans. IMPORTANCE The incidence of drug-resistant bacteria found in the environment is increasing together with the levels of antibiotic-resistant bacteria that cause infections. The COVID-19 pandemic has shed new light on the importance of monitoring emerging threats and finding early warning systems. Therefore, to mitigate the antimicrobial resistance burden, the monitoring and early identification of antibiotic-resistant bacteria in hot spots, such as wastewater treatment plants, are required to combat the occurrence and spread of antibiotic-resistant bacteria. Here, we applied a PhenePlate system as a phenotypic screening method for genomic surveillance and discovered a dominant and persistent E. coli clone ST2797 with a multidrug resistance pattern and equivalent phenotypic characteristics to those of the major pandemic lineages, namely, ST131 and ST648, which frequently carry ESBL genes. This study highlights the continuous surveillance and report of multidrug resistant bacteria with the potential to spread in One Health settings.202337260395
183880.9997An overview of carbapenem-resistant organisms from food-producing animals, seafood, aquaculture, companion animals, and wildlife. Carbapenem resistance (CR) is a major global health concern. CR is a growing challenge in clinical settings due to its rapid dissemination and low treatment options. The characterization of its molecular mechanisms and epidemiology are highly studied. Nevertheless, little is known about the spread of CR in food-producing animals, seafood, aquaculture, wildlife, their environment, or the health risks associated with CR in humans. In this review, we discuss the detection of carbapenem-resistant organisms and their mechanisms of action in pigs, cattle, poultry, seafood products, companion animals, and wildlife. We also pointed out the One Health approach as a strategy to attempt the emergency and dispersion of carbapenem-resistance in this sector and to determine the role of carbapenem-producing bacteria in animals among human public health risk. A higher occurrence of carbapenem enzymes in poultry and swine has been previously reported. Studies related to poultry have highlighted P. mirabilis, E. coli, and K. pneumoniae as NDM-5- and NDM-1-producing bacteria, which lead to carbapenem resistance. OXA-181, IMP-27, and VIM-1 have also been detected in pigs. Carbapenem resistance is rare in cattle. However, OXA- and NDM-producing bacteria, mainly E. coli and A. baumannii, are cattle's leading causes of carbapenem resistance. A high prevalence of carbapenem enzymes has been reported in wildlife and companion animals, suggesting their role in the cross-species transmission of carbapenem-resistant genes. Antibiotic-resistant organisms in aquatic environments should be considered because they may act as reservoirs for carbapenem-resistant genes. It is urgent to implement the One Health approach worldwide to make an effort to contain the dissemination of carbapenem resistance.202337397005
184090.9997Extended-Spectrum β-Lactamases (ESBL) Producing Bacteria in Animals. Animals have been identified as potential reservoirs and vectors of resistance genes, with studies showing that Gram-negative bacteria can acquire resistance through the horizontal transmission of resistance genes on plasmids. It is important to understand the distribution of antimicrobial-resistant bacteria and their drug-resistant genes in animals. Previous review articles mostly focused on a single bacterium or a single animal. Our objective is to compile all ESBL-producing bacteria isolated from various animals in recent years and provide a comprehensive viewpoint. Using a thorough PubMed literature search spanning from 1 January 2020 to 30 June 2022, studies exploring extended-spectrum beta-lactamase (ESBL) producing bacteria in animals were included. ESBL-producing bacteria are present in animals from various countries around the world. The most common sources of these bacteria were farm animals, and the most frequently isolated bacteria were Escherichia coli and Klebsiella pneumoniae. The most detected ESBL genes were bla(TEM), bla(SHV), and bla(CTX-M). The presence of ESBL-producing bacteria in animals highlights the importance of the One Health approach to address the issue of antibiotic resistance. Further research is needed to better understand the epidemiology and mechanisms of the spread of ESBL-producing bacteria in animal populations and their potential impact on human and animal health.202337107023
5003100.9997Updates on the global dissemination of colistin-resistant Escherichia coli: An emerging threat to public health. Colistin drug resistance is an emerging public health threat worldwide. The adaptability, existence and spread of colistin drug resistance in multiple reservoirs and ecological environmental settings is significantly increasing the rate of occurrence of multidrug resistant (MDR) bacteria such as Escherichia coli (E. coli). Here, we summarized the reports regarding molecular and biological characterization of mobile colistin resistance gene (mcr)-positive E. coli (MCRPEC), originating from diverse reservoirs, including but not limited to humans, environment, waste water treatment plants, wild, pets, and food producing animals. The MCRPEC revealed the abundance of clinically important resistance genes, which are responsible for MDR profile. A number of plasmid replicon types such as IncI2, IncX4, IncP, IncX, and IncFII with a predominance of IncI2 were facilitating the spread of colistin resistance. This study concludes the distribution of multiple sequence types of E. coli carrying mcr gene variants, which are possible threat to "One Health" perspective. In addition, we have briefly explained the newly known mechanisms of colistin resistance i.e. plasmid-encoded resistance determinant as well as presented the chromosomally-encoded resistance mechanisms. The transposition of ISApl1 into the chromosome and existence of intact Tn6330 are important for transmission and stability for mcr gene. Further, genetic environment of co-localized mcr gene with carbapenem-resistance or extended-spectrum β-lactamases genes has also been elaborated, which is limiting human beings to choose last resort antibiotics. Finally, environmental health and safety control measures along with spread mechanisms of mcr genes are discussed to avoid further propagation and environmental hazards of colistin resistance.202134364270
1868110.9997Genomic 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
5725120.9997Commonality of Multidrug-Resistant Klebsiella pneumoniae ST348 Isolates in Horses and Humans in Portugal. Multidrug-resistant (MDR) Klebsiella pneumoniae is considered a major global concern by the World Health Organization. Evidence is growing on the importance of circulation of MDR bacterial populations between animals and humans. Horses have been shown to carry commensal isolates of this bacterial species and can act as human MDR bacteria reservoirs. In this study, we characterized an extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae sequence type (ST) 348 isolate from a horse, an ST reported for the first time in an animal, using next-generation sequencing. We compared it with six other MDR K. pneumoniae ST348 human isolates previously identified in health-care facilities in Portugal using a core genome multi-locus sequence typing approach to evaluate a possible genetic link. The horse isolate was resistant to most of the antimicrobials tested, including 3rd generation cephalosporins, fluoroquinolones, and aminoglycosides, and presented several antimicrobial resistance genes, including bla (ESBL). Twenty-one allele differences were found between the horse isolate and the most similar human isolate, suggesting a recent common ancestor. Other similarities were observed regarding the content on antimicrobial resistance genes, plasmid incompatibility groups, and capsular and somatic antigens. This study illustrates the relevance of the dissemination of MDR strains, and enhances that identification of these types of bacterial strains in both human and veterinary settings is of significant relevance in order to understand and implement combined control strategies for MDR bacteria in animals and humans.201931379799
1842130.9997Emergence 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
1877140.9997Prevalence 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
1901150.9997Discerning the dissemination mechanisms of antibiotic resistance genes through whole genome sequencing of extended-spectrum beta-lactamase (ESBL)-producing E. coli isolated from veterinary clinics and farms in South Korea. Extended-spectrum beta-lactamase (ESBL)-producing bacteria are resistant to most beta-lactams, including third-generation cephalosporins, limiting the treatment methods against the infections they cause. In this study, we performed whole genome sequencing of ESBL-producing E. coli to determine the mechanisms underlying the dissemination of antibiotic resistance genes. We analyzed 141 ESBL-producing isolates which had been collected from 16 veterinary clinics and 16 farms in South Korea. Long- and short-read sequencing platforms were used to obtain high-quality assemblies. The results showed that bla(CTX-M) is the dominant ESBL gene type found in South Korea. The spread of bla(CTX-M) appears to have been facilitated by both clonal spread between different host species and conjugation. Most bla(CTX-M) genes were found associated with diverse mobile genetic elements that may contribute to the chromosomal integration of the genes. Diverse incompatibility groups of bla(CTX-M)-harboring plasmids were also observed, which allows their spread among a variety of bacteria. Comprehensive whole genome sequence analysis was useful for the identification of the most prevalent types of ESBL genes and their dissemination mechanisms. The results of this study suggest that the propagation of ESBL genes can occur through clonal spread and plasmid-mediated dissemination, and that suitable action plans should be developed to prevent further propagation of these genes.202438554973
1847160.9997Resistance to Carbapenems in Non-Typhoidal Salmonella enterica Serovars from Humans, Animals and Food. Non-typhoidal serovars of Salmonella enterica (NTS) are a leading cause of food-borne disease in animals and humans worldwide. Like other zoonotic bacteria, NTS have the potential to act as reservoirs and vehicles for the transmission of antimicrobial drug resistance in different settings. Of particular concern is the resistance to critical "last resort" antimicrobials, such as carbapenems. In contrast to other Enterobacteriaceae (e.g., Klebsiella pneumoniae, Escherichia coli, and Enterobacter, which are major nosocomial pathogens affecting debilitated and immunocompromised patients), carbapenem resistance is still very rare in NTS. Nevertheless, it has already been detected in isolates recovered from humans, companion animals, livestock, wild animals, and food. Five carbapenemases with major clinical importance-namely KPC (Klebsiella pneumoniae carbapenemase) (class A), IMP (imipenemase), NDM (New Delhi metallo-β-lactamase), VIM (Verona integron-encoded metallo-β-lactamase) (class B), and OXA-48 (oxacillinase, class D)-have been reported in NTS. Carbapenem resistance due to the production of extended spectrum- or AmpC β-lactamases combined with porin loss has also been detected in NTS. Horizontal gene transfer of carbapenemase-encoding genes (which are frequently located on self-transferable plasmids), together with co- and cross-selective adaptations, could have been involved in the development of carbapenem resistance by NTS. Once acquired by a zoonotic bacterium, resistance can be transmitted from humans to animals and from animals to humans through the food chain. Continuous surveillance of resistance to these "last resort" antibiotics is required to establish possible links between reservoirs and to limit the bidirectional transfer of the encoding genes between S. enterica and other commensal or pathogenic bacteria.201829642473
1875170.9997Mobile Colistin Resistance (mcr) Gene-Containing Organisms in Poultry Sector in Low- and Middle-Income Countries: Epidemiology, Characteristics, and One Health Control Strategies. Mobile colistin resistance (mcr) genes (mcr-1 to mcr-10) are plasmid-encoded genes that threaten the clinical utility of colistin (COL), one of the highest-priority critically important antibiotics (HP-CIAs) used to treat infections caused by multidrug-resistant and extensively drug-resistant bacteria in humans and animals. For more than six decades, COL has been used largely unregulated in the poultry sector in low- and middle-income countries (LMICs), and this has led to the development/spread of mcr gene-containing bacteria (MGCB). The prevalence rates of mcr-positive organisms from the poultry sector in LMICs between January 1970 and May 2023 range between 0.51% and 58.8%. Through horizontal gene transfer, conjugative plasmids possessing insertion sequences (ISs) (especially ISApl1), transposons (predominantly Tn6330), and integrons have enhanced the spread of mcr-1, mcr-2, mcr-3, mcr-4, mcr-5, mcr-7, mcr-8, mcr-9, and mcr-10 in the poultry sector in LMICs. These genes are harboured by Escherichia, Klebsiella, Proteus, Salmonella, Cronobacter, Citrobacter, Enterobacter, Shigella, Providencia, Aeromonas, Raoultella, Pseudomonas, and Acinetobacter species, belonging to diverse clones. The mcr-1, mcr-3, and mcr-10 genes have also been integrated into the chromosomes of these bacteria and are mobilizable by ISs and integrative conjugative elements. These bacteria often coexpress mcr with virulence genes and other genes conferring resistance to HP-CIAs, such as extended-spectrum cephalosporins, carbapenems, fosfomycin, fluoroquinolone, and tigecycline. The transmission routes and dynamics of MGCB from the poultry sector in LMICs within the One Health triad include contact with poultry birds, feed/drinking water, manure, poultry farmers and their farm workwear, farming equipment, the consumption and sale of contaminated poultry meat/egg and associated products, etc. The use of pre/probiotics and other non-antimicrobial alternatives in the raising of birds, the judicious use of non-critically important antibiotics for therapy, the banning of nontherapeutic COL use, improved vaccination, biosecurity, hand hygiene and sanitization, the development of rapid diagnostic test kits, and the intensified surveillance of mcr genes, among others, could effectively control the spread of MGCB from the poultry sector in LMICs.202337508213
3306180.9996Using Culture-Enriched Phenotypic Metagenomics for Targeted High-Throughput Monitoring of the Clinically Important Fraction of the β-Lactam Resistome. High bacterial community diversity and complexity greatly challenge the cost-efficient monitoring of clinically prevalent antibiotic-resistant bacteria, which are usually present as rare and important populations involved in the environmental dissemination of clinical resistance. Here, we introduce culture-enriched phenotypic metagenomics that integrates culture enrichment, phenotypic screening, and metagenomic analyses as an emerging standardized methodology for targeted resistome monitoring and apply it to decipher the extended-spectrum β-lactam resistome in a municipal wastewater treatment plant (WWTP) and its receiving river. The results showed that clinically prevalent carbapenemase genes (e.g., the NDM and KPC families) and extended-spectrum β-lactamase genes (e.g., the CTX-M, TEM, and OXA families) were prevalent in the WWTP and showed prominent potential in horizontal dissemination. Strikingly, carbapenem and polymyxin resistance genes co-occurred in the highly virulent nosocomial pathogens Enterobacter kobei and Citrobacter freundii. Overall, this study exemplifies phenotypic metagenomics for high-throughput surveillance of a targeted clinically important fraction of antibiotic resistomes and substantially expands current knowledge on extended-spectrum β-lactam resistance in WWTPs.202235930686
1554190.9996Genetic evolution and clinical impact in extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae. The emergence of extended-spectrum β-lactamase (ESBL)-producing bacteria, particularly Escherichia coli and Klebsiella pneumoniae, is now a critical concern for the development of therapies against bacterial infection. ESBLs consist of three major genetic groups: TEM, SHV, and CTX-M types. Nosocomial infections due to TEM and SHV-producing K. pneumoniae strains were frequently documented until the late 1990s. The number of reports on community-acquired infections caused by CTX-M-producing E. coli strains have dramatically increased over the last decade; however, K. pneumoniae strains, of either the TEM or SHV types, are persistent and important ESBL producers. The spread of ESBL genes is associated with various mobile genetic elements, such as transposons, insertion sequences, and integrons. The rapid dissemination of ESBL genes of the CTX-M type may be related to highly complicated genetic structures. These structures harboring ESBL genes and mobile elements are found in a variety of plasmids, which often carry many other antibiotic resistance genes. Multidrug-resistant CTX-M-15-producing E. coli strains disseminate worldwide. Efficient mobile elements and plasmids may have accelerated the genetic diversity and the rapid spread of ESBL genes, and their genetic evolution has caused an emerging threat to the bacteria for which few effective drugs have been identified.201121689785