Global dissemination of a multidrug resistant Escherichia coli clone

Abstract

Escherichia coli sequence type 131 (ST131) is a globally disseminated, multidrug resistant (MDR) clone responsible for a high proportion of urinary tract and bloodstream infections. The rapid emergence and successful spread of E. coli ST131 is strongly associated with several factors, including resistance to fluoroquinolones, high virulence gene content, the possession of the type 1 fimbriae FimH30 allele, and the production of the CTX-M-15 extended spectrum β-lactamase (ESBL). Here, we used genome sequencing to examine the molecular epidemiology of a collection of E. coli ST131 strains isolated from six distinct geographical locations across the world spanning 2000-2011. The global phylogeny of E. coli ST131, determined from whole-genome sequence data, revealed a single lineage of E. coli ST131 distinct from other extraintestinal E. coli strains within the B2 phylogroup. Three closely related E. coli ST131 sublineages were identified, with little association to geographic origin. The majority of single-nucleotide variants associated with each of the sublineages were due to recombination in regions adjacent to mobile genetic elements (MGEs). The most prevalent sublineage of ST131 strains was characterized by fluoroquinolone resistance, and a distinct virulence factor and MGE profile. Four different variants of the CTX-M ESBL-resistance gene were identified in our ST131 strains, with acquisition of CTX-M-15 representing a defining feature of a discrete but geographically dispersed ST131 sublineage. This study confirms the global dispersal of a single E. coli ST131 clone and demonstrates the role of MGEs and recombination in the evolution of this important MDR pathogen. bacterial evolution | genomics | phylogeography | genomic epidemiology M any multidrug-resistant (MDR) bacterial strains are now recognized as belonging to clones that originate in a specific locale, country, or even globally. Escherichia coli sequence type 131 (ST131) is one such recently emerged and globally disseminated MDR pandemic clone responsible for community and hospital-acquired urinary tract and bloodstream infections. E. coli ST131 was identified in 2008 as a major clone linked to the spread of the CTX-M-15 extended-spectrum β-lactamase (ESBL) resistance (1-3). Since then, E. coli ST131 has also been strongly associated with fluoroquinolone resistance, and coresistance to aminoglycosides and trimethoprim-sulfamethoxazole (4-6). Alarmingly, strains of E. coli ST131 resistant to carbapenems have also been reported (7, 8), further limiting treatment options for this clone.E. coli ST131 belongs to the B2 phylogenetic subgroup I, with most isolates characterized as serotype O25b:H4 (1). Epidemiology studies using pulse-field gel electrophoresis (PFGE) have demonstrated that E. coli ST131 strains exhibit diversity, with some dominant PFGE pulsotypes including the UK epidemic strain A (9) and pulsotype 968 (10, 11) widely distributed across the globe. More recently, a typing scheme using the type 1 fimbriae fimH adhesin gene revealed that a la...

Correlated Mutations and Homologous Recombination Within Bacterial Populations

“…As mentioned above, the value of r inferred for each sample is equal to the ratio of the number of polymorphisms due to recombination vs. the number of de novo mutations. In both species, r ) 1; indicating that the diversity introduced by recombination dominates sample diversity, which is consistent with previous results (Price et al 2013;Chewapreecha et al 2014;Petty et al 2014). Yet, since r varies substantially from clade to clade, it suggests that real variability exists between subpopulations as far as the portions of the shared gene pool that each is able to access.…”

High prevalence of Escherichia coli sequence type 131 among antimicrobial-resistant E. coli isolates from geriatric patients

“…The prevalence of H30-Rx subclone among our H30 isolates was 18.6 %, which is substantially lower than the .70 % among H30 ST131 isolates preselected by specific resistance phenotypes (Banerjee et al, 2013b;. H30-Rx described previously among isolates from Europe and North America was almost always ESBL-positive and had CTX-M-15 Petty et al, 2014;Price et al, 2013). Here, only three of the eight H30-Rx isolates were ESBL-producers.…”

“…H30, designated according to the fimH30 variant, is currently the most prevalent subclone of ST131 (Nicolas-Chanoine et al, 2014). Two studies involving whole genome sequencing of ST131 isolates collected from multiple countries came to the same conclusion that fluoroquinolone resistance within ST131 was confined almost entirely to the H30 subclone and that CTX-M-15 producers clustered within a nested subclone, designated H30-Rx (Petty et al, 2014;Price et al, 2013 and 16.9 to 66.2 %, respectively, depending on the isolate sources and selection criteria (Banerjee et al, 2013b;Price et al, 2013). The majority of the ST131 isolates that have been tested for the H30 and H30-Rx subclones were collected from North America and Europe; relatively few isolates were from Asia (Banerjee et al, 2013a, b;Colpan et al, 2013;Johnson et al, 2013Johnson et al, , 2014Tchesnokova et al, 2013).…”

“…H30, designated according to the fimH30 variant, is currently the most prevalent subclone of ST131 (Nicolas-Chanoine et al, 2014). Two studies involving whole genome sequencing of ST131 isolates collected from multiple countries came to the same conclusion that fluoroquinolone resistance within ST131 was confined almost entirely to the H30 subclone and that CTX-M-15 producers clustered within a nested subclone, designated H30-Rx (Petty et al, 2014;Price et al, 2013 …”

Blocking Yersiniabactin Import Attenuates Extraintestinal Pathogenic Escherichia coli in Cystitis and Pyelonephritis and Represents a Novel Target To Prevent Urinary Tract Infection

“…In addition, yersiniabactin is disproportionately associated with antibiotic-resistant strains, including Ͼ90% of strains of the E. coli sequence type 131 (ST131), an alarming pandemic multidrug-resistant (MDR) clonal group (48)(49)(50)(51), and Ͼ60% of respiratory carbapenemase-producing K. pneumoniae strains, compared to 10% of susceptible K. pneumoniae strains (41). Novel antimicrobial agents or vaccines that target yersiniabactin iron transport or other pathogen-associated nutrient acquisition systems may provide an effective strategy to combat the rising surge of antibiotic-resistant common infections.…”