Genomic epidemiology reveals geographical clustering of multidrug-resistant Escherichia coli sequence type (ST)131 associated with bacteraemia in Wales, United Kingdom

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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A Comprehensive Account of Escherichia coli Sequence Type 131 in Wastewater Reveals an Abundance of Fluoroquinolone-Resistant Clade A Strains

Applied and Environmental Microbiology ◽

10.1128/aem.01913-19 ◽

2019 ◽

Vol 86 (4) ◽

Author(s):

Thomas J. Finn ◽

Lena Scriver ◽

Linh Lam ◽

Mai Duong ◽

Gisele Peirano ◽

...

Keyword(s):

Escherichia Coli ◽

International Health ◽

Multidrug Resistant ◽

Screening Strategy ◽

Sequence Type ◽

High Rate ◽

Dominant Form ◽

Content Type ◽

Comprehensive Account ◽

Tract Infections

ABSTRACT In the ten years since its discovery, the Escherichia coli clone sequence type 131 (ST131) has become a major international health threat, with the multidrug-resistant and extended-spectrum β-lactamase (ESBL)-producing clade C emerging as the globally dominant form. ST131 has previously been isolated from wastewater; however, most of these studies selectively screened for ESBL-producing organisms, thereby missing the majority of remaining ST131 clades. In this study, we used a high-throughput PCR-based screening strategy to comprehensively examine wastewater for the presence of ST131 over a 1-year period. Additional multiplex PCRs were used to differentiate clades and obtain an unbiased account of the total ST131 population structure within the collection. Furthermore, antimicrobial susceptibility profiles of all ST131-positive samples were tested against a range of commonly used antibiotics. From a total of over 3,762 E. coli wastewater samples, 1.86% (n = 70) tested positive for ST131, with the majority being clade A isolates. In total, 63% (n = 44) were clade A, 29% (n = 20) were clade B, 1% (n = 1) were clade C0, 6% (n = 4) were clade C1, and 1% (n = 1) were clade C2. In addition, a very high rate of resistance to commonly used antibiotics among wastewater isolates is reported, with 72.7% (n = 32) of clade A resistant to ciprofloxacin and high rates of resistance to gentamicin, sulfamethoxazole-trimethoprim, and tetracycline in clades that are typically sensitive to antibiotics. IMPORTANCE ST131 is a global pathogen. This clone causes urinary tract infections and is frequently isolated from human sources. However, little is known about ST131 from environmental sources. With the widely reported increase in antibiotic concentrations found in wastewater, there is additional selection pressure for the emergence of antibiotic-resistant ST131 in this niche. The unbiased screening approach reported herein revealed that previously antibiotic-sensitive lineages of ST131 are now resistant to commonly used antibiotics present in wastewater systems and may be capable of surviving UV sterilization. This is the most comprehensive account of ST131 in the wastewater niche to date and an important step in better understanding the ecology of this global pathogen.

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Success of Escherichia coli O25b:H4 Sequence Type 131 Clade C Associated with a Decrease in Virulence

Infection and Immunity ◽

10.1128/iai.00576-20 ◽

2020 ◽

Vol 88 (12) ◽

Author(s):

Marion Duprilot ◽

Alexandra Baron ◽

François Blanquart ◽

Sara Dion ◽

Cassandra Pouget ◽

...

Keyword(s):

Escherichia Coli ◽

Phylogenetic Analyses ◽

Multidrug Resistant ◽

Sequence Type ◽

Content Type ◽

Gut Colonization ◽

Clade B ◽

Clade C ◽

Severe Infections

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.

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OXA-181-Producing Extraintestinal Pathogenic Escherichia coli Sequence Type 410 Isolated from a Dog in Portugal

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02298-19 ◽

2020 ◽

Vol 64 (4) ◽

Author(s):

Michael Brilhante ◽

Juliana Menezes ◽

Adriana Belas ◽

Claudia Feudi ◽

Stefan Schwarz ◽

...

Keyword(s):

Escherichia Coli ◽

Virulence Genes ◽

Skin Infection ◽

Multidrug Resistant ◽

Sequence Type ◽

Whole Genome ◽

Content Type ◽

E Coli ◽

Pathogenic Escherichia Coli ◽

Tract Infections

ABSTRACT Two multidrug-resistant and carbapenemase-producing Escherichia coli clones of sequence type 410 were isolated from fecal samples of a dog with skin infection on admission to an animal hospital in Portugal and 1 month after discharge. Whole-genome sequencing revealed a 126,409-bp Col156/IncFIA/IncFII multidrug resistance plasmid and a 51,479-bp IncX3 blaOXA-181-containing plasmid. The chromosome and plasmids carried virulence genes characteristic for uropathogenic E. coli, indicating that dogs may carry multidrug-resistant E. coli isolates related to those causing urinary tract infections in humans.

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Diversification of Colonization Factors in a Multidrug-Resistant Escherichia coli Lineage Evolving under Negative Frequency-Dependent Selection

mBio ◽

10.1128/mbio.00644-19 ◽

2019 ◽

Vol 10 (2) ◽

Cited By ~ 38

Author(s):

Alan McNally ◽

Teemu Kallonen ◽

Christopher Connor ◽

Khalil Abudahab ◽

David M. Aanensen ◽

...

Keyword(s):

Public Health ◽

Escherichia Coli ◽

Anaerobic Metabolism ◽

Multidrug Resistant ◽

Frequency Dependent ◽

Frequency Dependent Selection ◽

Content Type ◽

E Coli ◽

Negative Frequency Dependent Selection ◽

Tract Infections

ABSTRACT Escherichia coli is a major cause of bloodstream and urinary tract infections globally. The wide dissemination of multidrug-resistant (MDR) strains of extraintestinal pathogenic E. coli (ExPEC) poses a rapidly increasing public health burden due to narrowed treatment options and increased risk of failure to clear an infection. Here, we present a detailed population genomic analysis of the ExPEC ST131 clone, in which we seek explanations for its success as an emerging pathogenic strain beyond the acquisition of antimicrobial resistance (AMR) genes. We show evidence for evolution toward separate ecological niches for the main clades of ST131 and differential evolution of anaerobic metabolism, key colonization, and virulence factors. We further demonstrate that negative frequency-dependent selection acting across accessory loci is a major mechanism that has shaped the population evolution of this pathogen. IMPORTANCE Infections with multidrug-resistant (MDR) strains of Escherichia coli are a significant global public health concern. To combat these pathogens, we need a deeper understanding of how they evolved from their background populations. By understanding the processes that underpin their emergence, we can design new strategies to limit evolution of new clones and combat existing clones. By combining population genomics with modelling approaches, we show that dominant MDR clones of E. coli are under the influence of negative frequency-dependent selection, preventing them from rising to fixation in a population. Furthermore, we show that this selection acts on genes involved in anaerobic metabolism, suggesting that this key trait, and the ability to colonize human intestinal tracts, is a key step in the evolution of MDR clones of E. coli.

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Genome Sequences of Five Multidrug-Resistant Escherichia coli Sequence Type 117 Isolates Recovered from Dairy Calves

Genome Announcements ◽

10.1128/genomea.00732-17 ◽

2017 ◽

Vol 5 (33) ◽

Cited By ~ 1

Author(s):

Seon-Woo Kim ◽

Jeffrey S. Karns ◽

Jo Ann S. Van Kessel ◽

Bradd J. Haley

Keyword(s):

Escherichia Coli ◽

Urinary Tract ◽

Urinary Tract Infections ◽

Multidrug Resistant ◽

Sequence Type ◽

Dairy Calves ◽

Genome Sequences ◽

Content Type ◽

Food Animals ◽

Tract Infections

ABSTRACT Escherichia coli sequence type 117 (ST117) strains have been recovered from poultry with colibacillosis, as well as from urinary tract infections and fatal septic infections in humans. To further investigate ST117 isolates recovered from nonpoultry food animals, we sequenced the genomes of five ST117 isolates from dairy calves in Pennsylvania.

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Three-Year Trend in Escherichia coli Antimicrobial Resistance among Children’s Urine Cultures in an Italian Metropolitan Area

Children ◽

10.3390/children8070597 ◽

2021 ◽

Vol 8 (7) ◽

pp. 597

Author(s):

Luca Pierantoni ◽

Laura Andreozzi ◽

Simone Ambretti ◽

Arianna Dondi ◽

Carlotta Biagi ◽

...

Keyword(s):

Escherichia Coli ◽

Metropolitan Area ◽

Bacterial Infections ◽

Asymptomatic Bacteriuria ◽

Multidrug Resistant ◽

Resistance Rate ◽

First Line ◽

E Coli ◽

First Line Therapy ◽

Tract Infections

Urinary tract infections (UTIs) are among the most common bacterial infections in children, and Escherichia coli is the main pathogen responsible. Several guidelines, including the recently updated Italian guidelines, recommend amoxicillin-clavulanic acid (AMC) as a first-line antibiotic therapy in children with febrile UTIs. Given the current increasing rates of antibiotic resistance worldwide, this study aimed to investigate the three-year trend in the resistance rate of E. coli isolated from pediatric urine cultures (UCs) in a metropolitan area of northern Italy. We conducted a retrospective review of E. coli-positive, non-repetitive UCs collected in children aged from 1 month to 14 years, regardless of a diagnosis of UTI, catheter colonization, urine contamination, or asymptomatic bacteriuria. During the study period, the rate of resistance to AMC significantly increased from 17.6% to 40.2% (p < 0.001). Ciprofloxacin doubled its resistance rate from 9.1% to 16.3% (p = 0.007). The prevalence of multidrug-resistant E. coli rose from 3.9% to 9.2% (p = 0.015). The rate of resistance to other considered antibiotics remained stable, as did the prevalence of extended spectrum beta-lactamases and extensively resistant E. coli among isolates. These findings call into question the use of AMC as a first-line therapy for pediatric UTIs in our population, despite the indications of recent Italian guidelines.

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Comparative Genomics ofEscherichia coliIsolated from Skin and Soft Tissue and Other Extraintestinal Infections

mBio ◽

10.1128/mbio.01070-17 ◽

2017 ◽

Vol 8 (4) ◽

Cited By ~ 12

Author(s):

Amit Ranjan ◽

Sabiha Shaik ◽

Nishant Nandanwar ◽

Arif Hussain ◽

Sumeet K. Tiwari ◽

...

Keyword(s):

Escherichia Coli ◽

Comparative Genomics ◽

Soft Tissue ◽

Multidrug Resistant ◽

Primary Concern ◽

Beta Lactamase ◽

Soft Tissue Infections ◽

E Coli ◽

Recent Emergence ◽

Tract Infections

ABSTRACTEscherichia 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 pathogenicE. 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, ExPECE. coliisolated 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). TheblaCTX-M-15genotype was observed in at least 70% of theE. coliisolates 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.IMPORTANCEInfections caused by extraintestinal pathogenicE. coli(ExPEC) are of global concern as they result in significant costs to health care facilities management. The recent emergence of a multidrug-resistant pandemic clone,Escherichia coliST131, is of primary concern as a global threat. In developing countries, such as India, skin and soft tissue infections (SSTIs) associated withE. coliare marginally addressed. In this study, we employed both genomic analysis and phenotypic assays to determine relationships, if any, among the ExPEC pathotypes. Similarity between antibiotic resistance and virulence profiles was observed, ST131 isolates from SSTIs were reported, and genomic similarities among strains isolated from different disease conditions were detected. This study provides functional molecular infection epidemiology insight into SSTI-associatedE. colicompared with ExPEC pathotypes.

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