Genomic and Functional Portrait of a Highly Virulent, CTX-M-15-Producing
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            30-Rx Subclone of Escherichia coli Sequence Type 131

Tiwari

et al. 2017

mBio

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104

Escherichia coli sequence type 131 (ST131), a pandemic clone responsible for the high incidence of extraintestinal pathogenic E. coli (ExPEC) infections, has been known widely for its contribution to the worldwide dissemination of multidrug resistance. Although other ExPEC-associated and extended-spectrum-β-lactamase (ESBL)-producing E. coli clones, such as ST38, ST405, and ST648 have been studied widely, no comparative genomic data with respect to other genotypes exist for ST131. In this study, comparative genomic analysis was performed for 99 ST131 E. coli strains with 40 genomes from three other STs, including ST38 (n = 12), ST405 (n = 10), and ST648 (n = 18), and functional studies were performed on five in-house strains corresponding to the four STs. Phylogenomic analysis results from this study corroborated with the sequence type-specific clonality. Results from the genome-wide resistance profiling confirmed that all strains were inherently multidrug resistant. ST131 genomes showed unique virulence profiles, and analysis of mobile genetic elements and their associated methyltransferases (MTases) has revealed that several of them were missing from the majority of the non-ST131 strains. Despite the fact that non-ST131 strains lacked few essential genes belonging to the serum resistome, the in-house strains representing all four STs demonstrated similar resistance levels to serum antibactericidal activity. Core genome analysis data revealed that non-ST131 strains usually lacked several ST131-defined genomic coordinates, and a significant number of genes were missing from the core of the ST131 genomes. Data from this study reinforce adaptive diversification of E. coli strains belonging to the ST131 lineage and provide new insights into the molecular mechanisms underlying clonal diversification of the ST131 lineage.

Section: Resultsmentioning

confidence: 99%

Comparative Genomic Analysis of Globally Dominant ST131 Clone with Other Epidemiologically Successful Extraintestinal Pathogenic Escherichia coli (ExPEC) Lineages

Tiwari

et al. 2017

mBio

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104

“…Twelve strains, comprising four from each of the three disease types, were subjected to comparative genomic analysis to obtain a broader perspective of the complexity of the E. coli disease types. Genome sequence data for four strains were also included from previous and ongoing studies, including reference strains Escherichia coli NA097 and NA114 ( 10 , 11 ), and eight isolates of this study were subjected to whole-genome sequencing (WGS). Whole-genome-based resistome profiles confirmed the strains to be multidrug resistant.…”

Section: Resultsmentioning

confidence: 99%

“…ExPEC is known to be evolving and disseminating globally via clonal expansion, with clones of similar genetic architectures but also demonstrating strain-specific features ( 11 , 18 ). Here, we observed similarities in virulence and resistance coordinates of strains belonging to sequence types (STs) ST131, ST38, ST68, ST405, and ST617.…”

Section: Discussionmentioning

confidence: 99%

Comparative Genomics of Escherichia coli Isolated from Skin and Soft Tissue and Other Extraintestinal Infections

Nandanwar

et al. 2017

mBio

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Escherichia coli, an intestinal Gram-negative bacterium, has been shown to be associated with a variety of diseases in addition to intestinal infections, such as urinary tract infections (UTIs), meningitis in neonates, septicemia, skin and soft tissue infections (SSTIs), and colisepticemia. Thus, for nonintestinal infections, it is categorized as extraintestinal pathogenic E. coli (ExPEC). It is also an opportunistic pathogen, causing cross infections, notably as an agent of zoonotic diseases. However, comparative genomic data providing functional and genetic coordinates for ExPEC strains associated with these different types of infections have not proven conclusive. In the study reported here, ExPEC E. coli isolated from SSTIs was characterized, including virulence and drug resistance profiles, and compared with isolates from patients suffering either pyelonephritis or septicemia. Results revealed that the majority of the isolates belonged to two pathogenic phylogroups, B2 and D. Approximately 67% of the isolates were multidrug resistant (MDR), with 85% producing extended-spectrum beta-lactamase (ESBL) and 6% producing metallo-beta-lactamase (MBL). The blaCTX-M-15 genotype was observed in at least 70% of the E. coli isolates in each category, conferring resistance to an extended range of beta-lactam antibiotics. Whole-genome sequencing and comparative genomics of the ExPEC isolates revealed that two of the four isolates from SSTIs, NA633 and NA643, belong to pandemic sequence type ST131, whereas functional characteristics of three of the ExPEC pathotypes revealed that they had equal capabilities to form biofilm and were resistant to human serum. Overall, the isolates from a variety of ExPEC infections demonstrated similar resistomes and virulomes and did not display any disease-specific functional or genetic coordinates.

“…Previous studies from our group have shown an endemic E. coli infection burden and the presence of clonal group ST131 isolates with NDM-1 (23)(24)(25)50). This study was aimed at detection, comprehensive characterization, and whole-genome sequence analysis of MBL-producing MDR organisms that can lead to successful infection.…”

Section: Discussionmentioning

confidence: 99%

“…(19)(20)(21)(22). Our previous studies have put forward strong evidence for the widespread occurrence of ST131 strains among extraintestinal infections in India and have also reported the existence of NDM-1-positive ST131 E. coli, thus representing a serious therapeutic challenge (23)(24)(25)(26)(27). This, together with the implication of NDM-producing strains globally, warrants serious attention of health care specialists and epidemiologists with respect to surveillance and resistance tracking in India and elsewhere so as to monitor threats locally and globally.…”

mentioning

confidence: 99%

Molecular Epidemiology and Genome Dynamics of New Delhi Metallo-β-Lactamase-Producing Extraintestinal Pathogenic Escherichia coli Strains from India

Antimicrob Agents Chemother

Mondal

et al. 2016

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cThe global dissemination and increasing incidence of carbapenem-resistant, Gram-negative organisms have resulted in acute public health concerns. Here, we present a retrospective multicenter study on molecular characterization of metallo-␤-lactamase (MBL)-producing clinical Escherichia coli isolates recovered from extraintestinal infections in two hospitals in Pune, India. We screened a large sample size of 510 E. coli isolates for MBL production wherein we profiled their molecular determinants, antimicrobial resistance phenotypes, functional virulence properties, genomic features, and transmission dynamics. Approximately 8% of these isolates were MBL producers, the majority of which were of the NDM-1 (69%) type, followed by NDM-5 (19%), NDM-4 (5.5%), and NDM-7 (5.5%). MBL producers were resistant to all antibiotics tested except for colistin, fosfomycin, and chloramphenicol, which were effective to various extents. Plasmids were found to be an effective means of dissemination of NDM genes and other resistance traits. All MBL producers adhered to and invaded bladder epithelial (T24) cells and demonstrated significant serum resistance. Genomic analysis of MBL-producing E. coli isolates revealed higher resistance but a moderate virulence gene repertoire. A subset of NDM-1-positive E. coli isolates was identified as dominant sequence type 101 (ST101) while two strains belonging to ST167 and ST405 harbored NDM-5. A majority of MBL-producing E. coli strains revealed unique genotypes, suggesting that they were clonally unrelated. Overall, the coexistence of virulence and carbapenem resistance in clinical E. coli isolates is of serious concern. Moreover, the emergence of NDM-1 among the globally dominant E. coli ST101 isolates warrants stringent surveillance and control measures.