Characterization of Escherichia coli bloodstream isolates associated with mortality

Abstract

Extra-intestinal pathogenic Escherichia coli (ExPEC) are the predominant cause of Gramnegative bloodstream infections. In this study, 20 E. coli isolates that were the causative agents of bacteraemia and subsequent mortality were characterized. Whole-genome sequencing was used to define the predominant sequence types (ST) among the isolates and to identify virulence factors associated with pathogenicity of ExPEC. The ability of the isolates to resist killing by both serum and polymorphonuclear leukocytes (PMNLs) was also assessed. In line with global trends, ST131 occurred most frequently among the bloodstream isolates and all isolates of this sequence type were multidrug resistant. Other common STs included ST73 and ST69. All isolates encoded multiple virulence factors across a range of categories, including factors involved in adhesion, immune evasion, iron acquisition and synthesis of toxins. None of these factors could be associated with serum and neutrophil resistance. The majority of isolates were resistant to the bactericidal action of serum and PMNLs, and most of those that were sensitive were isolated from patients with compromised immunity. INTRODUCTIONRates of Escherichia coli bacteraemia have increased steadily in recent years (de Kraker et al., 2013). Concurrently, rates of multidrug resistant (MDR) E. coli infections are on the rise. In particular, the predominant extra-intestinal pathogenic E. coli (ExPEC) global lineage sequence type (ST) 131 is frequently associated with fluoroquinolone resistance and production of extended-spectrum b-lactamases (ESBLs) (Nicolas-Chanoine et al., 2014).Unlike other commensals found in the gastrointestinal tract (GT), ExPEC have an associated array of virulence factors that allow survival outside of this setting. Many of these virulence factors have been horizontally acquired and vary from strain to strain (Dobrindt et al., 2003). They can be classed into adhesins, protectins, iron acquisition systems and toxins (Köhler & Dobrindt, 2011). Adhesins, such as the type 1 fimbriae, contribute to colonization of the urinary tract (UT) epithelium (Kaper et al., 2004;Mulvey et al., 2000; Ulett et al., 2013). The UT is the most common source of infection in cases of bacteraemia (Russo & Johnson, 2003). Access to the bloodstream follows an ascending infection in which the F1C and P fimbriae play a role (Kaper et al., 2004;Mulvey et al., 2000). Many other adhesins have been associated with pathogenesis of E. coli, including S fimbriae, the Hek adhesin, antigen 43, the temperature-sensitive haemagglutinin (Tsh), F9 fimbriae and the Iha adhesin (Fagan & Smith, 2007; Köhler & Dobrindt, 2011;Ulett et al., 2007;Wurpel et al., 2014).ExPEC that cross the tubular epithelial cell barrier and enter the bloodstream can induce a powerful host inflammatory response, resulting in sepsis. Sepsis is associated with high rates of morbidity and mortality (Laupland et al., 2008;Russo & Johnson, 2003). To survive in the bloodstream, E. coli have to resist immune defences of the host, includin...

Systematic longitudinal survey of invasive Escherichia coli in England demonstrates a stable population structure only transiently disturbed by the emergence of ST131

“…The fact that some of the genotypes from the (in silico) PCR did not present monophyletic clades made it difficult to assign all isolates to phylogroups without the use of a phylogenetic tree. The pattern of prevalence of STs is consistent with previous studies of isolates associated with urinary sepsis or bloodstream infection; for example, during a similar time period in Ireland the most frequent STs were ST131, ST73 and ST69 (Miajlovic et al 2016) and the E. coli from the BSAC Bacteraemia Resistance Surveillance Programme have the same most common profiles (CC73, CC131 and CC95) as this combined collection from BSAC and CUH (Day et al 2016). This also shows that the collections from BSAC and CUH are similar when STs are considered.…”

Pic-Producing Escherichia coli Induces High Production of Proinflammatory Mediators by the Host Leading to Death by Sepsis

“…Bloodstream infections have been related to the various pathovars of E. coli [13][14][15]. The strains that cause bacteremia have several virulence factors, including those involved with adhesion, immune system evasion, acquisition of iron, toxins production, and resistance to bactericidal action of the serum [16,17]. The presence of these factors can ensure the persistence of these bacteria in the blood and dissemination through the organism and can consequently trigger a severe inflammatory response resulting in sepsis [18,19].…”

Escherichia coli sequence type 73 as a cause of community acquired urinary tract infection in men and women in Rio de Janeiro, Brazil

“…Some of these clones, such as ST131, ST69, ST95 and ST73, predominate as cause of community-acquired urinary tract infections (UTI) and blood stream infections (BSI) (Riley 2014; Miajlovic et al 2015). The reasons for such predominance are unclear; however, the pathogenic potential and resistance to antimicrobials are frequently described explanations.…”