Liberation of host heme by Clostridioides difficile-mediated damage enhances Enterococcus faecalis fitness during infection.
Liberation of host heme by Clostridioides difficile-mediated damage enhances Enterococcus faecalis fitness during infection.
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艰难梭菌产生的毒素破坏结肠上皮并导致强烈的炎症反应。这种上皮屏障的破坏显著改变了艰难梭菌感染肠道的营养状况。艰难梭菌感染（CDI）期间毒素介导的营养重构对常驻微生物群的影响在很大程度上仍未被探索。一组机会致病菌肠球菌在CDI期间茁壮成长，但尚不清楚它们采用什么策略在这种改变的环境中生存。在这里，我们证明了粪肠球菌，一种血红素营养不良者，利用艰难梭菌毒素介导的损伤来获得宿主血红素以增强适应性。具体来说，从艰难梭菌感染的肠道获得的血红素被粪肠杆菌用来填充血红素依赖性细胞色素并进行有氧呼吸。这种适应性优势是艰难梭菌毒素介导的损伤所特有的，因为感染无毒素的艰难梭菌株并不会为粪肠杆菌提供适应性优势。最后，有针对性地破坏粪肠杆菌细胞色素（cydABDC）操纵子导致艰难梭菌感染肠道的适应性缺陷。总之，这项工作表明，艰难梭菌毒素重塑肠道生态系统，并以依赖cydabdc的方式改善粪肠杆菌的适应性。这些数据进一步强调，越来越多的证据表明艰难梭菌和肠球菌之间的合作伙伴关系对CDI的易感性和严重程度具有影响。艰难梭状芽孢杆菌和粪肠球菌是两种具有重大公共卫生意义的病原体。这两种细菌都在人类胃肠道中定植，在那里它们以恶化疾病结果的方式相互作用。我们表明，与艰难梭菌感染（CDI）相关的损伤释放有利于粪肠杆菌的营养物质。一种特殊的营养物质，血红素，使粪肠杆菌能够利用氧气产生能量，并在肠道中更好地生长。了解这些种间相互作用的机制可以为CDI的治疗策略提供信息。
Toxin production by Clostridioides difficile damages the colonic epithelium and leads to a robust inflammatory response. This disruption of the epithelial barrier markedly alters the nutritional landscape in the C. difficile-infected gut. The impact of toxin-mediated nutritional remodeling during C. difficile infection (CDI) on resident microbiota remains largely unexplored. One group of opportunistic pathogens, the enterococci, thrive during CDI, but it is unclear what strategies they employ to survive in this altered environment. Here, we demonstrate that Enterococcus faecalis, a heme auxotroph, takes advantage of C. difficile toxin-mediated damage to acquire host heme for enhanced fitness. Specifically, heme acquired from the C. difficile-infected gut is used by E. faecalis to populate a heme-dependent cytochrome and aerobically respire. This fitness advantage is specific to C. difficile toxin-mediated damage, as infection with a toxin-null strain of C. difficile does not provide E. faecalis with a fitness advantage. Finally, targeted disruption of the E. faecalis cytochrome (cydABDC) operon leads to a fitness defect in the C. difficile-infected gut. Together, this work demonstrates that C. difficile toxin remodels the gut ecosystem and improves the fitness of E. faecalis in a cydABDC-dependent manner. These data further highlight growing evidence of a cooperative partnership between C. difficile and enterococci that has implications on susceptibility to and severity of CDI. Clostridioides difficile and Enterococcus faecalis are two pathogens of great public health importance. Both bacteria colonize the human gastrointestinal tract where they are known to interact in ways that worsen disease outcomes. We show that the damage associated with C. difficile infection (CDI) releases nutrients that benefit E. faecalis. One particular nutrient, heme, allows E. faecalis to use oxygen to generate energy and grow better in the gut. Understanding the mechanisms of these interspecies interactions could inform therapeutic strategies for CDI.
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DOI：
10.1126/science.aam9949
发表时间：
2017-08-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Byndloss MX;Olsan EE;Rivera-Chávez F;Tiffany CR;Cevallos SA;Lokken KL;Torres TP;Byndloss AJ;Faber F;Gao Y;Litvak Y;Lopez CA;Xu G;Napoli E;Giulivi C;Tsolis RM;Revzin A;Lebrilla CB;Bäumler AJ
通讯作者：
Bäumler AJ
影响因子：
9.4
作者：
Joensen, Katrine Grimstrup;Scheutz, Flemming;Aarestrup, Frank M.
通讯作者：
Aarestrup, Frank M.
影响因子：
4.9
作者：
Fujitani, Shigeki;George, W. Lance;Murthy, A. Rekha
通讯作者：
Murthy, A. Rekha
DOI：
10.1093/jac/dkaa345
发表时间：
2020-12-01
期刊：
The Journal of antimicrobial chemotherapy
影响因子：
--
作者：
Bortolaia V;Kaas RS;Ruppe E;Roberts MC;Schwarz S;Cattoir V;Philippon A;Allesoe RL;Rebelo AR;Florensa AF;Fagelhauer L;Chakraborty T;Neumann B;Werner G;Bender JK;Stingl K;Nguyen M;Coppens J;Xavier BB;Malhotra-Kumar S;Westh H;Pinholt M;Anjum MF;Duggett NA;Kempf I;Nykäsenoja S;Olkkola S;Wieczorek K;Amaro A;Clemente L;Mossong J;Losch S;Ragimbeau C;Lund O;Aarestrup FM
通讯作者：
Aarestrup FM
影响因子：
6.4
作者：
Cevallos, Stephanie A.;Lee, Jee-Yon;Baumler, Andreas J.
通讯作者：
Baumler, Andreas J.