scholarly journals Escherichia coli ST131: a multidrug-resistant clone primed for global domination

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 195 ◽  
Author(s):  
Johann D.D. Pitout ◽  
Rebekah DeVinney

A single extra-intestinal pathogenic Escherichia coli (ExPEC) clone, named sequence type (ST) 131, is responsible for millions of global antimicrobial-resistant (AMR) infections annually. Population genetics indicate that ST131 consists of different clades (i.e. A, B, and C); however, clade C is the most dominant globally. A ST131 subclade, named C1-M27, is emerging in Japan and has been responsible for the recent increase in AMR ExPEC in that country. The sequential acquisition of several virulence and AMR genes associated with mobile genetic elements during the 1960s to 1980s primed clade C (and its subclades C1 and C2) for success in the 1990s to 2000s. IncF plasmids with F1:A2:B20 and F2:A1:B replicons have shaped the evolution of the C1 and C2 subclades. It is possible that ST131 is a host generalist with different accessory gene profiles. Compensatory mutations within the core genome of this clone have counterbalanced the fitness cost associated with IncF plasmids. ST131 clade C had dramatically changed the population structure of ExPEC, but it still remains unclear which features of this clade resulted in one of the most unprecedented AMR successes of the 2000s.

2015 ◽  
Vol 61 (9) ◽  
pp. 647-652 ◽  
Author(s):  
Natalia Fernández-Romero ◽  
María Pilar Romero-Gómez ◽  
Marta Mora-Rillo ◽  
Jesús Rodríguez-Baño ◽  
Lorena López-Cerero ◽  
...  

Extraintestinal pathogenic Escherichia coli (ExPEC) are among the most frequently isolated bacterial pathogens in hospitals. They are considered opportunistic pathogens and are found mostly in urinary and bloodstream infections. They are genetically diverse, and many studies have sought associations between genotypes or virulence genes and infection site, severity, or outcome, with varied, often contradictory, results. To understand these difficulties, we have analyzed the diversity patterns in the core genomes and virulomes of more than 500 ExPEC isolates from 5 different collections. The core genome was analyzed using a multilocus sequence type-based single-nucleotide polymorphism (SNP) pyrosequencing approach, while the virulence gene content (the virulome) was studied by polymerase chain reaction detection of 25 representative genes. SNP typing showed a similar population structure in the different collections: half of the isolates belong to a few sequence types (5 to 8), while the other half is composed of a large diversity of sequence types that are found once or twice. Sampling analysis by rarefaction plots of SNP profiles showed saturation curves indicative of a limited diversity. Contrary to this, the virulome shows an extremely high diversity, with almost as many gene profiles as isolates, and linear, nonsaturating, rarefaction plots, even within sequence types. These data show that genetic exchange rates are very heterogeneous along the chromosome, being much higher in the virulome fraction of the genome than in the core genome.


Author(s):  
Jorge A. Moura de Sousa ◽  
Eduardo P. C. Rocha

Bacteriophages (phages) are bacterial parasites that can themselves be parasitized by phage satellites. The molecular mechanisms used by satellites to hijack phages are sometimes understood in great detail, but the origins, abundance, distribution and composition of these elements are poorly known. Here, we show that P4-like elements are present in more than 30% of the genomes of Enterobacterales, and in almost half of those of Escherichia coli , sometimes in multiple distinct copies. We identified over 1000 P4-like elements with very conserved genetic organization of the core genome and a few hotspots with highly variable genes. These elements are never found in plasmids and have very little homology to known phages, suggesting an independent evolutionary origin. Instead, they are scattered across chromosomes, possibly because their integrases are often exchanged with other elements. The rooted phylogenies of hijacking functions are correlated and suggest longstanding coevolution. They also reveal broad host ranges in P4-like elements, as almost identical elements can be found in distinct bacterial genera. Our results show that P4-like phage satellites constitute a very distinct, widespread and ancient family of mobile genetic elements. They pave the way for studying the molecular evolution of antagonistic interactions between phages and their satellites. This article is part of the theme issue ‘The secret lives of microbial mobile genetic elements’.


2021 ◽  
Author(s):  
Jorge Moura de Sousa ◽  
Eduardo P. C. Rocha

Bacteriophages (phages) are bacterial parasites that can themselves be parasitized by phage satellites. The molecular mechanisms used by satellites to hijack phages are sometimes understood in great detail, but the origins, abundance, distribution, and composition of these elements are poorly known. Here, we show that P4-like elements are present in more than 10% of the genomes of Enterobacterales, and in almost half of those of Escherichia coli, sometimes in multiple distinct copies. We identified over 1000 P4-like elements with very conserved genetic organization of the core genome and a few hotspots with highly variable genes. These elements are never found in plasmids and have very little homology to known phages, suggesting an independent evolutionary origin. Instead, they are scattered across chromosomes, possibly because their integrases are often exchanged with other elements. The rooted phylogenies of hijacking functions are correlated and suggest longstanding co-evolution. They also reveal broad host ranges in P4-like elements, since almost identical elements can be found in distinct bacterial genuses. Our results show that P4-like phage satellites constitute a very distinct, widespread and ancient family of mobile genetic elements. They pave the way for studying the molecular evolution of antagonistic interactions between phages and their satellites.


Author(s):  
Hazem Ramadan ◽  
Ahmed M. Soliman ◽  
Lari M. Hiott ◽  
Mohammed Elbediwi ◽  
Tiffanie A. Woodley ◽  
...  

In this study, multidrug-resistant (MDR) Escherichia coli isolates from retail food and humans assigned into similar Multilocus Sequence Types (MLST) were analyzed using whole genome sequencing (WGS). In silico analysis of assembled sequences revealed the existence of multiple resistance genes among the examined E. coli isolates. Of the six CTX-M-producing isolates from retail food, blaCTX-M-14 was the prevalent variant identified (83.3%, 5/6). Two plasmid-mediated fosfomycin resistance genes, fosA3, and fosA4, were detected from retail food isolates (one each from chicken and beef), where fosA4 was identified in the chicken isolate 82CH that also carried the colistin resistance gene mcr-1. The blaCTX-M-14 and fosA genes in retail food isolates were located adjacent to insertion sequences ISEcp1 and IS26, respectively. Sequence analysis of the reconstructed mcr-1 plasmid (p82CH) showed 96–97% identity to mcr-1-carrying IncI2 plasmids previously identified in human and food E. coli isolates from Egypt. Hierarchical clustering of core genome MLST (HierCC) revealed clustering of chicken isolate 82CH, co-harboring mcr-1 and fosA4 genes, with a chicken E. coli isolate from China at the HC200 level (≤200 core genome allelic differences). As E. coli co-harboring mcr-1 and fosA4 genes has only been recently reported, this study shows rapid spread of this genotype that shares similar genetic structures with regional and international E. coli lineages originating from both humans and food animals. Adopting WGS-based surveillance system is warranted to facilitate monitoring the international spread of MDR pathogens.


2021 ◽  
Vol 7 (9) ◽  
Author(s):  
Rebecca J. Hall ◽  
Fiona J. Whelan ◽  
Elizabeth A. Cummins ◽  
Christopher Connor ◽  
Alan McNally ◽  
...  

The pangenome contains all genes encoded by a species, with the core genome present in all strains and the accessory genome in only a subset. Coincident gene relationships are expected within the accessory genome, where the presence or absence of one gene is influenced by the presence or absence of another. Here, we analysed the accessory genome of an Escherichia coli pangenome consisting of 400 genomes from 20 sequence types to identify genes that display significant co-occurrence or avoidance patterns with one another. We present a complex network of genes that are either found together or that avoid one another more often than would be expected by chance, and show that these relationships vary by lineage. We demonstrate that genes co-occur by function, and that several highly connected gene relationships are linked to mobile genetic elements. We find that genes are more likely to co-occur with, rather than avoid, another gene in the accessory genome. This work furthers our understanding of the dynamic nature of prokaryote pangenomes and implicates both function and mobility as drivers of gene relationships.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S136-S136
Author(s):  
Lalitagauri M Deshpande ◽  
Andrew P Davis ◽  
F Fredrik Dyrkell ◽  
Dimitrios Amellos ◽  
Mariana Castanheira

Abstract Background Increasing antimicrobial resistance (R) among Escherichia coli (EC) isolates can be associated with the expansion of the pandemic sequence type (ST) 131 that harbors virulence factors and causes more severe infections when compared with other antimicrobial-R EC. We evaluated the core genome MLST (cgMLST) profiles and R genes using the bioinformatics tool 1928D to evaluate the epidemiology of a global ST131 EC collection and unrelated STs. Methods A total of 259 EC clinical isolates belonging to ST131 (n = 206), ST131-single loci variant (SLV; n = 25), and 28 non-ST131 isolates collected from 27 countries during 2016–2018 were selected. Whole-genome sequencing FASTQ files were uploaded to the 1928D pipeline to generate MLST, cgMLST and R gene prediction. cgMLST assignment was based on comparing >2,500 genes. Results Among 231 ST131 and SLV EC isolates, 7 clades were identified (3 major [178 isolates]; Table) applying cgMLST allele distance (ad) of ≤50 as a cutoff. A total of 21 isolates were not assigned to clades (>50 ad from ST131 and SLV). Based on >95% concordance, 11 alleles differentiated clades II and III from clade I, while 6 alleles separated clades I and III from clade II. Isolates in clades I to IV were ciprofloxacin R (MIC, ≥4 mg/L); clades I and III predominantly carried blaCTX-M-15 (39/43 and 61/66), blaOXA-1 (35/43 and 43/66), and aac(6’)-Ib-cr (39/43, 45/66) while clade II carried blaCTX-M-14-like and rarely aac(6’)Ib-cr (3/69). The most ad between the 7 ST131 clades was 216, while unrelated STs showed variable ad among isolates within that ST. Isolates bellowing to ST1193 were closely related genetically (ad of 30), but other STs had more variability among isolates (ST167, ad 552; ST38, ad 150; and ST69, ad 179). Conclusion 1928D is a robust platform for epidemiological analysis of isolates, providing additional granularity when compared with MLST. Clades II and III were closely related, but carried different blaCTX-M genes, while clades I and III were not as closely related, but both carried blaCTX-M-15, blaOXA-1, and aac(6’)Ib-cr. These findings suggest that these clades might have acquired R genes at different points in their genetic evolution. A threshold of ≤50 (cgMLST distance) was useful for classifying isolates into clades. Disclosures All authors: No reported disclosures.


2020 ◽  
Vol 88 (12) ◽  
Author(s):  
Marion Duprilot ◽  
Alexandra Baron ◽  
François Blanquart ◽  
Sara Dion ◽  
Cassandra Pouget ◽  
...  

ABSTRACT Escherichia coli O25b:H4 sequence type 131 (ST131), which is resistant to fluoroquinolones and which is a producer of CTX-M-15, is globally one of the major extraintestinal pathogenic E. coli (ExPEC) lineages. Phylogenetic analyses showed that multidrug-resistant ST131 strains belong to clade C, which recently emerged from clade B by stepwise evolution. It has been hypothesized that features other than multidrug resistance could contribute to this dissemination since other major global ExPEC lineages (ST73 and ST95) are mostly antibiotic susceptible. To test this hypothesis, we compared early biofilm production, presence of ExPEC virulence factors (VFs), and in vivo virulence in a mouse sepsis model in 19 and 20 epidemiologically relevant strains of clades B and C, respectively. Clade B strains were significantly earlier biofilm producers (P < 0.001), carriers of more VFs (P = 4e−07), and faster killers of mice (P = 2e−10) than clade C strains. Gene inactivation experiments showed that the H30-fimB and ibeART genes were associated with in vivo virulence. Competition assays in sepsis, gut colonization, and urinary tract infection models between the most anciently diverged strain (B1 subclade), one C1 subclade strain, and a B4 subclade recombining strain harboring some clade C-specific genetic events showed that the B1 strain always outcompeted the C1 strain, whereas the B4 strain outcompeted the C1 strain, depending on the mouse niches. All these findings strongly suggest that clade C evolution includes a progressive loss of virulence involving multiple genes, possibly enhancing overall strain fitness by avoiding severe infections, even if it comes at the cost of a lower colonization ability.


2021 ◽  
Author(s):  
Rhys Thomas White ◽  
Matthew J Bull ◽  
Clare R Barker ◽  
Julie M Arnott ◽  
Mandy Wootton ◽  
...  

Increasing resistance to third-generation cephalosporins (3GCs) threatens public health, as these antimicrobials are prescribed as empirical therapies for systemic infections caused by Gram-negative bacteria. Resistance to 3GCs in urinary tract infections (UTIs) and bacteraemia is associated with the globally disseminated, multidrug-resistant, uropathogenic Escherichia coli sequence type (ST)131. This study combines the epidemiology of E.coli blood culture surveillance with whole-genome sequencing (WGS) to investigate ST131 associated with bacteraemia in Wales between 2013 and 2014. This population-based prospective genomic analysis investigated temporal, geographic, and genomic risk factors. To identify spatial clusters and lineage diversity, we contextualised 142 genomes collected from twenty hospitals, against a global ST131 population (n=181). All three major ST131 clades are represented across Wales, with clade C/H30 predominant (n=102/142, 71.8%). Consistent with global findings, Welsh strains of clade C/H30 contain β-lactamase genes from the blaCTX-M-1 group (n=65/102, 63.7%), which confers resistance to 3GCs. In Wales, the majority of clade C/H30 strains belonged to sub-clade C2/H30Rx (n=88/151, 58.3%), whereas sub-clade C1/H30R strains were less common (n=14/67, 20.9%). A sub-lineage unique to Wales was identified within the C2/H30Rx sub-clade (named GB-WLS.C2/H30Rx) and is defined by six non-recombinogenic single-nucleotide polymorphisms (SNPs), including a missense variant in febE (ferric enterobactin transport protein) and fryC (fructose-like permease IIC component), and the loss of the capsular biosynthesis genes encoding the K5 antigen. Bayesian analysis predicted that GB-WLS.C2/H30Rx diverged from a common ancestor (CA) most closely related to a Canadian strain between 1998 and 1999. Further, our analysis suggests a descendent of GB-WLS.C2/H30Rx arrived through an introduction to North Wales circa 2002, spread and persists in the geographic region, causing a cluster of cases (CA emerged circa 2009) with a maximum pair-wise distance of 30 non-recombinogenic SNPs. This limited genomic diversity likely depicts local transmission within the community in North Wales. This investigation emphasises the value of genomic epidemiology, allowing detection of suspected transmission clusters and the spread of genetically similar/identical strains in local areas. These analyses will enable targeted and timely public health interventions.


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