Bachmann Verena, Kostiuk Benjamin, Unterweger Daniel, Diaz-Satizabal Laura, Ogg Stephen, Pukatzki Stefan
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
PLoS Negl Trop Dis. 2015 Aug 28;9(8):e0004031. doi: 10.1371/journal.pntd.0004031. eCollection 2015.
The causative agent of cholera, Vibrio cholerae, regulates its diverse virulence factors to thrive in the human small intestine and environmental reservoirs. Among this pathogen's arsenal of virulence factors is the tightly regulated type VI secretion system (T6SS). This system acts as an inverted bacteriophage to inject toxins into competing bacteria and eukaryotic phagocytes. V. cholerae strains responsible for the current 7th pandemic activate their T6SS within the host. We established that T6SS-mediated competition occurs upon T6SS activation in the infant mouse, and that this system is functional under anaerobic conditions. When investigating the intestinal host factors mucins (a glycoprotein component of mucus) and bile for potential regulatory roles in controlling the T6SS, we discovered that once mucins activate the T6SS, bile acids can further modulate T6SS activity. Microbiota modify bile acids to inhibit T6SS-mediated killing of commensal bacteria. This interplay is a novel interaction between commensal bacteria, host factors, and the V. cholerae T6SS, showing an active host role in infection.
霍乱的病原体霍乱弧菌会调节其多种毒力因子，以便在人类小肠和环境储存库中繁衍。在这种病原体的毒力因子库中，有受到严格调控的VI型分泌系统（T6SS）。该系统就像一个反向噬菌体，将毒素注入竞争性细菌和真核吞噬细胞中。引发当前第七次霍乱大流行的霍乱弧菌菌株会在宿主体内激活其T6SS。我们证实，T6SS介导的竞争在幼鼠体内T6SS激活时发生，并且该系统在厌氧条件下也能发挥作用。在研究肠道宿主因子粘蛋白（黏液的一种糖蛋白成分）和胆汁对T6SS的潜在调控作用时，我们发现，一旦粘蛋白激活T6SS，胆汁酸就能进一步调节T6SS的活性。微生物群会对胆汁酸进行修饰，以抑制T6SS介导的对共生细菌的杀伤。这种相互作用是共生细菌、宿主因子和霍乱弧菌T6SS之间的一种新型相互作用，表明宿主在感染过程中发挥着积极作用。
