Johnston Brian D, Clabots Connie, Bender Tricia, Porter Stephen B, van den Dobbelsteen Germie, Poolman Jan, Thuras Paul, Johnson James R
Departments of Medicine and Psychiatry, University of Minnesota, Minneapolis 55455, MN, USA.
Infectious Diseases (111F), Minneapolis VA Health Care System, Minneapolis 55417, MN, USA.
Pathogens. 2023 Apr 15;12(4):603. doi: 10.3390/pathogens12040603.
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.
卓越的肠道定植能力可能是序列型131（O25b:K+:H4）的多重耐药30R亚克隆在流行病学上取得巨大成功的基础。为了为预防定植措施的制定提供依据，我们研究了30R肠道定植的全身免疫相关因素。通过选择性培养和PCR对人类志愿者的粪便样本进行30R筛查。通过酶免疫测定法对受试者血清中抗O25 IgG（代表30R）和抗O6 IgG（一般代表非30R）水平进行初始评估，并持续评估长达14个月。全血在与菌株JJ1886（30R；O25b:K+:H4）或CFT073（非30R；O6:K2:H1）孵育后，检测抗原刺激下IFNγ、TNFα、IL-4、IL-10和IL-17的释放。获得了三个主要发现。首先，30R定植的受试者抗O25 IgG水平显著高于对照组，但抗O6 IgG水平相似，表明对30R定植有IgG反应。其次，抗O25和抗O6 IgG水平随时间稳定。第三，相对于菌株CFT073（非30R），30R定植的受试者在对菌株JJ1886（30R）的反应中表现出比对照组更低的TNFα和IL-10释放，这与TNFα对30R反应低下可能易导致30R定植一致。因此，30R定植的宿主表现出持续的血清抗O25 IgG反应以及对30R的TNFα反应潜在缺陷，这可能是预防定植的潜在靶点。
