An exceptional gut-colonizing ability may underlie the dramatic epidemiological success of the multidrug-resistant H30R 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 H30R intestinal colonization. Human volunteers’ fecal samples were screened for H30R by selective culture and PCR. Subjects were assessed by enzyme immunoassay for serum levels of anti-O25 IgG (representing H30R) and anti-O6 IgG (representing non-H30 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 (H30R; O25b:K+:H4) or CFT073 (non-H30; O6:K2:H1). Three main findings were obtained. First, H30R-colonized subjects had significantly higher anti-O25 IgG levels than controls, but similar anti-O6 IgG levels, suggesting an IgG response to H30R colonization. Second, anti-O25 and anti-O6 IgG levels were stable over time. Third, H30R-colonized subjects exhibited a lower TNFα and IL-10 release than controls in response to strain JJ1886 (H30R) relative to strain CFT073 (non-H30R), consistent with TNFα hypo-responsiveness to H30R possibly predisposing to H30R colonization. Thus, H30R-colonized hosts exhibit a sustained serum anti-O25 IgG response and an underlying deficit in TNFα responsiveness to H30R that could potentially be addressed for colonization prevention.
Bibliographical noteFunding Information:
This work was supported in part by Office of Research and Development, U.S. Department of Veterans Affairs. Funding included VA Merit Review grant # 1 I01 CX000920-01A1, “E. coli ST131 and intestinal colonization”; VA Merit Review grant # 2I01CX000920-04, “Gut reservoir of E. coli ST131”; NIH Antibacterial Resistance Leadership Group (ARLG), award number UM1AI104681, subproject “Surveillance for persistent intestinal colonization with E. coli ST131 (SPICES)” (all to JRJ). The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication. The views expressed are strictly those of the authors and do not necessarily reflect those of their institutions or the funders.
© 2023 by the authors.
- antigen-stimulated cytokine release
- Escherichia coli ST131-H30
- intestinal colonization
PubMed: MeSH publication types
- Journal Article