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There is an urgent need to understand the global epidemiological landscape of carbapenem-resistant Escherichia coli (CREC). Here we provide combined genomic and phenotypic characterization of the emergence of a CREC clone from the ST410 lineage. We show that the clone expands with a single plasmid, within which there is frequent switching of the ca...
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... strains were recovered from blood, sputum, urine, wound secretion, bile, pleural fluid, and ascites, suggesting that CREC is associated with various types of infections such as bloodstream infection, pneumonia, and urinary tract infection (Table 1). All CREC strains were resistant to imipenem (minimum inhibitory concentrations [MIC], 8 to >256 mg/l), meropenem (MIC, 32 to >256 mg/l), piperacillin/tazobactam, ceftazidime, and ceftazidime/avibactam but were susceptible to tigecycline (Table 2 and Supplementary Dataset 1). Most strains were resistant to ciprofloxacin (resistance rate, 96%), trimethoprim/sulfamethoxazole (88%), aztreonam (76%), and gentamicin (68%), while most were susceptible to aztreonam/avibactam (susceptible rate, 92%), colistin (88%), and amikacin (72%) ( Table 2). ...Context 2
... CREC strains were resistant to imipenem (minimum inhibitory concentrations [MIC], 8 to >256 mg/l), meropenem (MIC, 32 to >256 mg/l), piperacillin/tazobactam, ceftazidime, and ceftazidime/avibactam but were susceptible to tigecycline (Table 2 and Supplementary Dataset 1). Most strains were resistant to ciprofloxacin (resistance rate, 96%), trimethoprim/sulfamethoxazole (88%), aztreonam (76%), and gentamicin (68%), while most were susceptible to aztreonam/avibactam (susceptible rate, 92%), colistin (88%), and amikacin (72%) ( Table 2). All of the 25 CREC were subjected to short read whole-genome sequencing and antimicrobial resistance genes were identified based on their draft genome sequences. ...Citations
... The second MDR-Ec strain used (Ec-042) was an OXA-181 producer belonging to ST410, a rapidly emerging pandemic clone particularly able to colonize the intestinal tract of humans and animals (Nigg et al., 2019;Moser et al., 2021;Pitout et al., 2024). As recorded for Ec-042 (Table 1), the ST410 lineage possesses patterns of VFs (e.g., fimbriae, bacteriocins) very similar to those of ST131 (Roer et al., 2018;Feng et al., 2019;Pitout et al., 2024). Therefore, it is not surprising that Ec-042 also rapidly colonized Z. morio larvae and persisted with a high bacterial load until T28 (~10 4 CFU/mL; Figure 2). ...
Finding strategies for decolonizing gut carriers of multidrug-resistant Escherichia coli (MDR-Ec) is a public-health priority. In this context, novel approaches should be validated in preclinical in vivo gut colonization models before being translated to humans. However, the use of mice presents limitations. Here, we used for the first time Zophobas morio larvae to design a new model of intestinal colonization (28-days duration, T28). Three hyperepidemic MDR-Ec producing extended-spectrum β-lactamases (ESBLs) or carbapenemases were administered via contaminated food to larvae for the first 7 days (T7): Ec-4901.28 (ST131, CTX-M-15), Ec-042 (ST410, OXA-181) and Ec-050 (ST167, NDM-5). Growth curve analyses showed that larvae became rapidly colonized with all strains (T7, ~106–7 CFU/mL), but bacterial load remained high after the removal of contaminated food only in Ec-4901.28 and Ec-042 (T28, ~103–4 CFU/mL). Moreover, larvae receiving a force-feeding treatment with INTESTI bacteriophage cocktail (on T7 and T10 via gauge needle) were decolonized by Ec-4901.28 (INTESTI-susceptible); however, Ec-042 and Ec-050 (INTESTI-resistant) did not. Initial microbiota (before administering contaminated food) was very rich of bacterial genera (e.g., Lactococcus, Enterococcus, Spiroplasma), but patterns were heterogeneous (Shannon diversity index: range 1.1–2.7) and diverse to each other (Bray–Curtis dissimilarity index ≥30%). However, when larvae were challenged with the MDR-Ec with or without administering bacteriophages the microbiota showed a non-significant reduction of the diversity during the 28-day experiments. In conclusion, the Z. morio larvae model promises to be a feasible and high-throughput approach to study novel gut decolonization strategies for MDR-Ec reducing the number of subsequent confirmatory mammalian experiments.
... E. coli ST131 is a global MDR clone associated with both community-associated infections and HAIs, with a multitude of resistance genes, including ESBLs, particularly bla CXM-15 , and quinolone resistance genes and virulence factors specifically associated with UTIs and bacteremia [68,69]. For E. coli, the results also reported ST167 and ST410, which are emerging global MDR bacterial clones associated with carbapenem resistance [70,71]. ...
Antimicrobial resistance is a global healthcare threat with significant clinical and economic consequences peaking at secondary and tertiary care hospitals where multidrug-resistant Gram-negative bacteria (MDR GNB) lead to poor outcomes. A prospective study was conducted between January and December 2019 for all invasive bloodstream infections (BSIs) secondary to MDR GNB in Qatar identified during routine microbiological service to examine their clinical, microbiological, and genomic characteristics. Out of 3238 episodes of GNB BSIs, the prevalence of MDR GNB was 13% (429/3238). The predominant MDR pathogens were Escherichia coli (62.7%), Klebsiella pneumoniae (20.4%), Salmonella species (6.6%), and Pseudomonas aeruginosa (5.3%), while out of 245 clinically evaluated patients, the majority were adult males, with the elderly constituting almost one-third of the cohort and with highest observed risk for prolonged hospital stays. The risk factors identified included multiple comorbidities, recent healthcare contact, previous antimicrobial therapy, and admission to critical care. The in-hospital mortality rate was recorded at 25.7%, associated with multiple comorbidities, admission to critical care, and the acquisition of MDR Pseudomonas aeruginosa. Resistant pathogens demonstrated high levels of antimicrobial resistance but noticeable susceptibility to amikacin and carbapenems. Genomic analysis revealed that Escherichia coli ST131 and Salmonella enterica ST1 were the predominant clones not observed with other pathogens.
... E. coli ST410 is an extraintestinal pathogen associated with multidrug resistance, and has been recognised as a high-risk international clone 15,16 . Whole-genome sequence analysis and evolutionary reconstruction of E. coli ST410 revealed that ST410 is comprised of two lineages, namely lineage A with fimH53 (A/H53) and lineage B with fimH24 (B/H24) 15 . ...
... Chen et al. reported that nearly all (292/293) ST410-B3 isolates analysed contain the ftsI YRIN insetion 17 . Over the past decade, there have been increasing reports of serious infections and possible hospital outbreaks involving the carbapenem-resistant ST410 sublineage B4/H24RxC in both developed and low-and middle-income countries 15,16,[20][21][22][23] . ...
... Resistance region variants present in the B5/H24RxC clone included an IS26-flanked segment that contained bla NDM-5 , bla TEM-1 , and sul1, aadA2 and dfrA12 in a class 1 integron. Although the bla NDM-5 gene was also present in some B4/ H24RxC isolates, in those it was found in variants of the bla OXA-181 carrying X3 plasmid (Fig. S6) as previously reported 16,17 . Core-genome genes and SNPs associated with B5/H24RxC MDR clone Pangenome-wide association study (pan-GWAS) using Scoary for the two clones identified 199 genes that were positively or negatively associated with B5/H24RxC ( Fig. 5; Supplementary Data 6). ...
Carbapenem-resistant Escherichia coli (CREC) ST410 has recently emerged as a major global health problem. Here, we report a shift in CREC prevalence in Chinese hospitals between 2017 and 2021 with ST410 becoming the most commonly isolated sequence type. Genomic analysis identifies a hypervirulent CREC ST410 clone, B5/H24RxC, which caused two separate outbreaks in a children’s hospital. It may have emerged from the previously characterised B4/H24RxC in 2006 and has been isolated in ten other countries from 2015 to 2021. Compared with B4/H24RxC, B5/H24RxC lacks the blaOXA-181-bearing X3 plasmid, but carries a F-type plasmid containing blaNDM-5. Most of B5/H24RxC also carry a high pathogenicity island and a novel O-antigen gene cluster. We find that B5/H24RxC grew faster in vitro and is more virulent in vivo. The identification of this newly emerged but already globally disseminated hypervirulent CREC clone, highlights the ongoing evolution of ST410 towards increased resistance and virulence.
... Surveys of the frequencies and global distribution of different ST410 clades are rare and showed that certain clades seem to be scarce (i.e., antimicrobial susceptible ST410-A and ST410-B1) while the MDR ST410-B2 and ST410-B3 subclades are common in France (17), China (18), and Denmark (19). Results from an E. coli carbapenemase global genomic survey (n = 229) with a large presentation of lower-and middle-income countries (LMICs) collected during 2015-2017 from 45 countries showed an overall dominance of the ST410-B3 subclade, consisting of nearly 80% of the total ST410 population (57). ...
... The ST410-A and ST410-B1 clades are susceptible to fluoroquinolones and do not contain QRDR mutations or plasmid-mediated fluoroquinolone resistance determinants. The ST410-B2 and ST410-B3 subclades are resistant to the fluoroquinolones due to the three typical E. coli QRDR mutations, namely gyrAS83L, gyrAD87N, and parC S80I (17,18,107). ST410-B2 and ST410-B3 also contained the parE mutation S458L ( Table 2). ...
... CTX-M types have been described among ST410-B2 and ST410-B3 subclades. The CTX-M-15 allele is by far the most frequent type of ESBL among ST410-B2 and ST410-B3 isolates (e.g., >80% prevalence) ( Table 2) (Table 2) (18,19,107). ...
Escherichia coli sequence type ST410 is an emerging carbapenemase-producing multidrug-resistant (MDR) high-risk One-Health clone with the potential to significantly increase carbapenem resistance among E. coli. ST410 belongs to two clades (ST410-A and ST410-B) and three subclades (ST410-B1, ST410-B2, and ST410-B3). After a fimH switch between clades ST410-A and ST410-B1, ST410-B2 and ST410-B3 subclades showed a stepwise progression toward developing MDR. (i) ST410-B2 initially acquired fluoroquinolone resistance (via homologous recombination) in the 1980s. (ii) ST410-B2 then obtained CMY-2, CTX-M-15, and OXA-181 genes on different plasmid platforms during the 1990s. (iii) This was followed by the chromosomal integration of blaCMY-2, fstl YRIN insertion, and ompC/ompF mutations during the 2000s to create the ST410-B3 subclade. (iv) An IncF plasmid “replacement” scenario happened when ST410-B2 transformed into ST410-B3: F36:31:A4:B1 plasmids were replaced by F1:A1:B49 plasmids (both containing blaCTX-M-15) followed by blaNDM-5 incorporation during the 2010s. User-friendly cost-effective methods for the rapid identification of ST410 isolates and clades are needed because limited data are available about the frequencies and global distribution of ST410 clades. Basic mechanistic, evolutionary, surveillance, and clinical studies are urgently required to investigate the success of ST410 (including the ability to acquire successive MDR determinants). Such information will aid with management and prevention strategies to curb the spread of carbapenem-resistant E. coli. The medical community can ill afford to ignore the spread of a global E. coli clone with the potential to end the carbapenem era.
... However, this is the first study, to the best of our knowledge, to determine the prevalence of the tss region within MDR ExPEC lineages. We have particularly focused on ST410 and ST131 as they are known to cause infections worldwide [35,36,45,46]. We have identified the evolutionary events that led to the loss of key structural T6SS components in these lineages via recombination or insertion events. ...
The repeated emergence of multi-drug-resistant (MDR) Escherichia coli clones is a threat to public health globally. In recent work, drug-resistant E. coli were shown to be capable of displacing commensal E. coli in the human gut. Given the rapid colonization observed in travel studies, it is possible that the presence of a type VI secretion system (T6SS) may be responsible for the rapid competitive advantage of drug-resistant E. coli clones. We employed large-scale genomic approaches to investigate this hypothesis. First, we searched for T6SS genes across a curated dataset of over 20 000 genomes representing the full phylogenetic diversity of E. coli . This revealed large, non-phylogenetic variation in the presence of T6SS genes. No association was found between T6SS gene carriage and MDR lineages. However, multiple clades containing MDR clones have lost essential structural T6SS genes. We characterized the T6SS loci of ST410 and ST131 and identified specific recombination and insertion events responsible for the parallel loss of essential T6SS genes in two MDR clones.
... This pattern was not seen in successful non-MDR ExPEC lineages such as ST73 [13]. Such allelic diversity in anaerobic metabolism genes has also been seen in ST167 and ST648 [12,14], and it was also shown that recombination of new alleles of fhu iron acquisition genes was the key evolutionary event underpinning the emergence the carbapenem-resistant B4/H24RxC clone in the ST410 lineage [15]. We hypothesise that these genetic adaptations may contribute to more effective colonisation of the mammalian gut. ...
Extra-intestinal pathogenic Escherichia coli (ExPEC) can cause a variety of infections outside of the intestine and are a major causative agent of urinary tract infections. Treatment of these infections is increasingly frustrated by antimicrobial resistance (AMR) diminishing the number of effective therapies available to clinicians. Incidence of multidrug resistance (MDR) is not uniform across the phylogenetic spectrum of E . coli . Instead, AMR is concentrated in select lineages, such as ST131, which are MDR pandemic clones that have spread AMR globally. Using a gnotobiotic mouse model, we demonstrate that an MDR E . coli ST131 is capable of out-competing and displacing non-MDR E . coli from the gut in vivo. This is achieved in the absence of antibiotic treatment mediating a selective advantage. In mice colonised with non-MDR E . coli strains, challenge with MDR E . coli either by oral gavage or co-housing with MDR E . coli colonised mice results in displacement and dominant intestinal colonisation by MDR E . coli ST131. To investigate the genetic basis of this superior gut colonisation ability by MDR E . coli , we assayed the metabolic capabilities of our strains using a Biolog phenotypic microarray revealing altered carbon metabolism. Functional pangenomic analysis of 19,571 E . coli genomes revealed that carriage of AMR genes is associated with increased diversity in carbohydrate metabolism genes. The data presented here demonstrate that independent of antibiotic selective pressures, MDR E . coli display a competitive advantage to colonise the mammalian gut and points to a vital role of metabolism in the evolution and success of MDR lineages of E . coli via carriage and spread.
... The E. coli ST410 strains, along with ST131, have been proposed as globally circulating strains of extraintestinal pathogenic E. coli (ExPEC) [10]. ExPEC bacteria are known to encode various extraintestinal virulence factors and have been attributed to various infectious diseases, including neonatal meningitis, urinary tract infections, bloodstream infections and pneumonia [42][43][44]. In these clinical situations, the administration of β-lactam antibiotics, including carbapenems, is an important treatment option. ...
The circulation of carbapenemase-producing Escherichia coli (CPEC) in our society is a serious concern for vulnerable patients in nosocomial environments. However, the genomic epidemiology of the circulation of CPEC bacteria among companion animals remains largely unknown. In this study, epidemiological analysis was conducted using complete genome identification of CPEC ST410 isolates obtained from companion animals. To estimate the genomic distance and relatedness of the isolates, a total of 37 whole-genome datasets of E. coli ST410 strains were downloaded and comparatively analysed. As a result of the analysis, the genomic structure of the chromosomes and plasmids was identified, revealing the genomic positions of multiple resistance and virulence genes. The isolates in this study were grouped into the subclade H24/RxC, with fimH24 , and substituted quinolone resistance-determining regions (QRDRs) and multiple beta-lactamases, including extended-spectrum β-lactamase (ESBL) and carbapenemase. In addition, the in silico comparison of the whole-genome datasets revealed unidentified ST410 H24/Rx subgroups, including either high pathogenicity islands (HPIs) or H21 serotypes. Considering the genetic variations and resistance gene dissemination of the isolates carried by companion animals, future approaches for preventive measurement must include the “One Health” perspective for public health in our society.
... The E. coli ST93 lineage has been detected at the animalhuman interface previously, associated with the carriage of the bla CTX-M and plasmid-mediated colistin-resistance (mcr-1) genes [63,64], and also shared between dog and owner [18]. The E. coli ST410 lineage is involved in the global epidemiological landscape of carbapenem resistance [65,66], with reports of interspecies transmission of CTX-M-producing strains between humans, companion animals, wildlife and the environment [67]. The E. coli ST457 lineage has been shown to display a remarkable ability to capture mobile genetic elements that carry and transmit genes encoding resistance to CIAs for human medicine in a broad host range [63,68]. ...
Extended-spectrum beta-lactamase (ESBL)- and plasmid-mediated cephalosporinase (AmpC)-producing Enterobacterales (ESBL/AmpC-E) are an increasing healthcare problem in both human and veterinary medicine. The aim of this study was to investigate the possible sharing of ESBL/AmpC-E strains between healthy companion animals and humans of the same household in Portugal (PT) and the United Kingdom (UK). In a prospective longitudinal study, between 2018 and 2020, faecal samples were collected from healthy dogs (n=90), cats (n=20) and their cohabiting humans (n=119) belonging to 41 PT and 44 UK households. Samples were screened for the presence of ESBL/AmpC-E and carbapenemase-producing bacteria. Clonal relatedness between animal and human strains was established by using REP-PCR fingerprinting method, followed by whole-genome sequencing (WGS) of selected strains. ESBL/AmpC-E strains were detected in companion animals (PT=12.7%, n=8/63; UK=8.5%, n=4/47) and humans (PT=20.7%, n=12/58; UK=6.6%, n=4/61) in at least one timepoint. REP-PCR identified paired multidrug-resistant ESBL/AmpC-producing Escherichia coli strains from companion animals and owners in two Portuguese households (4.8%) and one UK household (2.3%). WGS analysis of nine E. coli strains from these three households confirmed that interhost sharing occurred only between the two animal-human pairs from Portugal. Three shared strains were identified: one CTX-M-15-producing E. coli strain in a cat-human pair (O15-H33-ST93) and two CTX-M-15- and CTX-M-55/CMY-2-producing E. coli strains, in a dog-human pair (O8:H9-ST410 and O11:H25-ST457, respectively) at different timepoints. These E. coli clonal lineages are human pandemic, highlighting the role of companion animals living in close contact with humans in the dissemination and persistence of antimicrobial resistance in the household environment.
... Global genomic surveillance has provided insight into the mechanisms and epidemiology of their spread, suggesting that capture of virulence and AMR determinants via horizontal gene transfer by so-called high risk clones results in fitness and/or colonisation advantages and subsequent global dissemination [6]. This phenomenon is well described in E. coli sequence type (ST) 131 [7], associated with the ESBL-encoding gene bla CTX-M-15 , but has also been recently described in other carbapenemase-associated E. coli lineages, such as ST167 [8] and ST410 [9]. ...
... To better describe the phylogeny of the three most common STs in our dataset, ST131, ST410 and ST167 in greater resolution, we inferred lineage-specific phylogenies using a map-to-reference approach, contextualised with publicly available genomes. We used previously curated multi-country collections of 862 ST131 genomes [37], 327 ST410 genomes [9], and 181 ST167 genomes [38]. For all isolates, we obtained available raw reads (n=108 genomes for ST167, n=327 for ST410 and n=862 for ST131), performed QC with fastQC v0.11.8 (https://www.bioinformatics.babraham.ac.uk/projects/ fastqc/) and multiqc v1.8 [39], trimmed raw reads with Trimmomatic v0.39 [40], removing adapter sequences and leading or trailing bases with phred score <4, bases with a mean score <20 (over a sliding window of four bases), and any reads with length below 36 following removal of low quality bases. ...
... CP034955.1, CP034956.1 and CP034957.1 from the bla NDM-5 -encoding ST410 strain SCEC020026 [9] as reference sequences. The unicycler-assembled ST410 strain resulted in nine contigs (4 670 094 bp; 127 483 bp; 98 229 bp; 33 870 bp; 2 088 bp; 245 bp; 194 bp; 165 bp; 119 bp); we did not include the chromosome (largest fragment) and the smallest four plasmids in the comparison as they are likely spurious assemblies; sequences below 200 bp furthermore get removed by default by genbank whole-genome upload as likely contaminants. ...
Escherichia coli is one of the most prevalent Gram-negative species associated with drug resistant infections. Strains that produce extended-spectrum beta-lactamases (ESBLs) or carbapenemases are both particularly problematic and disproportionately impact resource limited healthcare settings where last-line antimicrobials may not be available. A large number of E. coli genomes are now available and have allowed insights into pathogenesis and epidemiology of ESBL E. coli but genomes from sub-Saharan Africa (sSA) are significantly underrepresented. To reduce this gap, we investigated ESBL-producing E. coli colonising adults in Blantyre, Malawi to assess bacterial diversity and AMR determinants and to place these isolates in the context of the wider population structure. We performed short-read whole-genome sequencing of 473 colonising ESBL E. coli isolated from human stool and contextualised the genomes with a previously curated multi-country collection of 10 146 E. coli genomes and sequence type (ST)-specific collections for our three most commonly identified STs. These were the globally successful ST131, ST410 and ST167, and the dominant ESBL genes were bla CTX-M , mirroring global trends. However, 37 % of Malawian isolates did not cluster with any isolates in the curated multicountry collection and phylogenies were consistent with locally spreading monophyletic clades, including within the globally distributed, carbapenemase-associated B4/H24RxC ST410 lineage. A single ST2083 isolate in this collection harboured a carbapenemase gene. Long read sequencing demonstrated the presence of a globally distributed ST410-associated carbapenemase carrying plasmid in this isolate, which was absent from the ST410 strains in our collection. We conclude there is a risk that carbapenem resistance in E. coli could proliferate rapidly in Malawi under increasing selection pressure, and that both ongoing antimicrobial stewardship and genomic surveillance are critical as local carbapenem use increases.
... ST410 clones have dispersed into various ecological niches worldwide, including humans, food-producing animals, companion animals, wild animals, food, and the environment (3)(4)(5)(6). More alarming is that the ST410 sublineage B4/H24RxC, often carrying carbapenem resistance determinants (bla OXA-181 and/or bla NDM-5 ), is rapidly emerging (6,7), and it is reported to be responsible for the global distribution of bla NDM-5 and bla OXA-181 genes (8). Of greater concern is the recent emergence of ST410 clones coproducing NDM-5 and OXA-181 in human clinical settings of several countries, such as Denmark, South Korea, Egypt, and Myanmar (9)(10)(11). ...
During a 2020 routine epidemiological investigation of carbapenem-resistant Enterobacterales at a local food market in Guangzhou, China, two Escherichia coli ST410 isolates coproducing NDM-5 and OXA-181 were obtained from environmental samples. Antimicrobial susceptibility testing, whole-genome sequencing, and conjugation assays were applied to identify their resistance phenotypes, phylogenetic relatedness, and genetic characteristics. Phylogenetic analysis showed that the two isolates were clonally related with only one core-genome single-nucleotide polymorphism (SNP) difference and clustered into a branch with 87 E. coli ST410 isolates deposited in GenBank. These 89 ST410 isolates were closely related (≤51 SNPs), and most were from humans in Southeast Asian countries (n = 47). A Vietnamese clinical isolate collected in 2017 showed the strongest epidemiological link (seven SNPs) to the two ST410 isolates detected in this study. Complete-genome analysis revealed that the carbapenem resistance determinants blaNDM-5 and blaOXA-181 were located on an IncF1:A1:B49-IncQ1 plasmid and IncX3 plasmid, respectively. Conjugation experiments confirmed that the IncX3 plasmid was self-transmissible while the IncF1:A1:B49-IncQ1 plasmid was nonconjugative. BLASTn analysis indicated that the two plasmids showed high similarity to other blaNDM-5-bearing IncF1:A1:B49-IncQ1 and blaOXA-181-bearing IncX3 plasmids from other countries. Altogether, the high similarity of the core genomes and plasmids between the ST410 isolates found in this study and those human source isolates from foreign countries suggested the clonal spread of E. coli ST410 strains and horizontal transmission of blaOXA-181-bearing IncX3 plasmids across Southeast Asian countries. Stringent sanitary management of food markets is important to prevent the dissemination of high-risk clones to the public. IMPORTANCE This is the first report of an Escherichia coli ST410 clone that coproduces NDM-5 and OXA-181 in China. The high similarity of the core genomes and plasmids between the ST410 isolates characterized in this study and human source isolates from foreign countries strongly suggests that this ST410 lineage is an international high-risk clone, highlighting the need for continuous global surveillance of ST410 clones.
