Colonization with Escherichia coli ST131- H 30R ( H 30R) Corresponds with Increased Serum Anti-O25 IgG Levels and Decreased TNFα and IL-10 Responsiveness to H 30R.

An exceptional gut-colonizing ability may underlie the dramatic epidemiological success of the multidrug-resistant H 30R subclone of Escherichia coli sequence type 131 (O25b:K+:H4). In order to inform the development of colonization-preventing measures, we studied systemic immune correlates of H 30R intestinal colonization. Human volunteers' fecal samples were screened for H 30R by selective culture and PCR. Subjects were assessed by enzyme immunoassay for serum levels of anti-O25 IgG (representing H 30R) and anti-O6 IgG (representing non- H 30 E. coli generally), initially and for up to 14 months. Whole blood was tested for the antigen-stimulated release of IFNγ, TNFα, IL-4, IL-10, and IL-17 after incubation with E. coli strains JJ1886 ( H 30R; O25b:K+:H4) or CFT073 (non- H 30; O6:K2:H1). Three main findings were obtained. First, H 30R-colonized subjects had significantly higher anti-O25 IgG levels than controls, but similar anti-O6 IgG levels, suggesting an IgG response to H 30R colonization. Second, anti-O25 and anti-O6 IgG levels were stable over time. Third, H 30R-colonized subjects exhibited a lower TNFα and IL-10 release than controls in response to strain JJ1886 ( H 30R) relative to strain CFT073 (non- H 30R), consistent with TNFα hypo-responsiveness to H 30R possibly predisposing to H 30R colonization. Thus, H 30R-colonized hosts exhibit a sustained serum anti-O25 IgG response and an underlying deficit in TNFα responsiveness to H 30R that could potentially be addressed for colonization prevention.