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

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