Colonization with Escherichia coli ST131-H30R (H30R) Corresponds with Increased Serum Anti-O25 IgG Levels and Decreased TNFα and IL-10 Responsiveness to H30R

Brian D Johnston; Connie Clabots; Tricia Bender; Stephen B Porter; Germie van den Dobbelsteen; Jan Poolman; Paul Thuras; James R Johnson

doi:10.3390/pathogens12040603

Colonization with Escherichia coli ST131-H30R (H30R) Corresponds with Increased Serum Anti-O25 IgG Levels and Decreased TNFα and IL-10 Responsiveness to H30R

Brian D Johnston, Connie Clabots, Tricia Bender, Stephen B Porter, Germie van den Dobbelsteen, Jan Poolman, Paul Thuras, James R Johnson

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Article number	603
Journal	Pathogens
Volume	12
Issue number	4
DOIs	https://doi.org/10.3390/pathogens12040603
State	Published - Apr 2023

Bibliographical note

Funding 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.

Publisher Copyright:
© 2023 by the authors.

Keywords

antigen-stimulated cytokine release
Escherichia coli ST131-H30
IgG
IL-10
intestinal colonization
TNFα

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title = "Colonization with Escherichia coli ST131-H30R (H30R) Corresponds with Increased Serum Anti-O25 IgG Levels and Decreased TNFα and IL-10 Responsiveness to H30R",

abstract = "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{\textquoteright} 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.",

keywords = "antigen-stimulated cytokine release, Escherichia coli ST131-H30, IgG, IL-10, intestinal colonization, TNFα",

author = "Johnston, {Brian D} and Connie Clabots and Tricia Bender and Porter, {Stephen B} and {van den Dobbelsteen}, Germie and Jan Poolman and Paul Thuras and Johnson, {James R}",

note = "Funding 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. Publisher Copyright: {\textcopyright} 2023 by the authors.",

year = "2023",

month = apr,

doi = "10.3390/pathogens12040603",

language = "English (US)",

volume = "12",

journal = "Pathogens",

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T1 - Colonization with Escherichia coli ST131-H30R (H30R) Corresponds with Increased Serum Anti-O25 IgG Levels and Decreased TNFα and IL-10 Responsiveness to H30R

AU - Johnston, Brian D

AU - Clabots, Connie

AU - Bender, Tricia

AU - Porter, Stephen B

AU - van den Dobbelsteen, Germie

AU - Poolman, Jan

AU - Thuras, Paul

AU - Johnson, James R

N1 - Funding 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. Publisher Copyright: © 2023 by the authors.

PY - 2023/4

Y1 - 2023/4

N2 - 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.

AB - 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.

KW - antigen-stimulated cytokine release

KW - Escherichia coli ST131-H30

KW - IgG

KW - IL-10

KW - intestinal colonization

KW - TNFα

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SN - 2076-0817

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JO - Pathogens

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ER -

Colonization with Escherichia coli ST131-H30R (H30R) Corresponds with Increased Serum Anti-O25 IgG Levels and Decreased TNFα and IL-10 Responsiveness to H30R

Abstract

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