Low-toxin Clostridioides difficile RT027 strains exhibit robust virulence.
Low-toxin Clostridioides difficile RT027 strains exhibit robust virulence.
复制标题
DOI：
10.1080/22221751.2022.2105260
复制
发表时间：
2022-12
影响因子：
13.2
通讯作者：
中科院分区：
文献类型：
--
作者：
Clostridioides difficile is a leading cause of healthcare-associated infections worldwide. Currently, there is a lack of consensus for an optimal diagnostic method for C. difficile infection (CDI). Multi-step diagnostic algorithms use enzyme immunosorbent analysis (EIA)-based detection of C. difficile toxins TcdA/TcdB in stool, premised on the rationale that EIA toxin-negative (Tox−) patients have less severe disease and shorter diarrhoea duration. The aim of this study was to characterize toxigenic (i.e. tcdA/tcdB-positive) C. difficile strains isolated from diarrheic patient stool with an EIA Tox− (i.e. “discrepant”) CDI diagnostic test result. Recovered strains were DNA fingerprinted (ribotyped), subjected to multiple toxin, genome and proteome evaluations, and assessed for virulence. Overall, of 1243 C. difficile-positive patient stool specimens from Southern Arizona hospitals, 31% were discrepant. For RT027 (the most prevalent ribotype)-containing specimens, 34% were discrepant; the corresponding RT027 isolates were cytotoxic to cultured fibroblasts, but their total toxin levels were comparable to, or lower than, the historic low-toxin-producing C. difficile strain CD630. Nevertheless, these low-toxin RT027 strains (LT-027) exhibited similar lethality to a clade-matched high-toxin RT027 strain in Golden Syrian hamsters, and heightened colonization and persistence in mice. Genomics and proteomics analyses of LT-027 strains identified unique genes and altered protein abundances, respectively, relative to high-toxin RT027 strains. Collectively, our data highlight the robust virulence of LT-027 C. difficile, provide a strong argument for reconsidering the clinical significance of a Tox− EIA result, and underscore the potential limitations of current diagnostic protocols.
登录
查看更多内容
影响因子：
9.8
作者：
Laabei M;Uhlemann AC;Lowy FD;Austin ED;Yokoyama M;Ouadi K;Feil E;Thorpe HA;Williams B;Perkins M;Peacock SJ;Clarke SR;Dordel J;Holden M;Votintseva AA;Bowden R;Crook DW;Young BC;Wilson DJ;Recker M;Massey RC
通讯作者：
Massey RC
影响因子：
6.4
作者：
Edwards, Adrianne N.;Anjuwon-Foster, Brandon R.;McBride, Shonna M.
通讯作者：
McBride, Shonna M.
影响因子：
6.7
作者：
Chu, Michele;Mallozzi, Michael J. G.;Vedantam, Gayatri
通讯作者：
Vedantam, Gayatri
影响因子：
4.2
作者：
Orozco-Aguilar J;Alfaro-Alarcón A;Acuña-Amador L;Chaves-Olarte E;Rodríguez C;Quesada-Gómez C
通讯作者：
Quesada-Gómez C
影响因子：
14.9
作者：
Letunic, Ivica;Bork, Peer
通讯作者：
Bork, Peer