Institute of Microbiology, ETH Zurich, Switzerland.
Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy en Josas, France.
Science. 2017 Mar 17;355(6330):1211-1215. doi: 10.1126/science.aaf8451. Epub 2017 Mar 16.
Bacteriophage transfer (lysogenic conversion) promotes bacterial virulence evolution. There is limited understanding of the factors that determine lysogenic conversion dynamics within infected hosts. A murine Typhimurium (Tm) diarrhea model was used to study the transfer of SopEΦ, a prophage from Tm SL1344, to Tm ATCC14028S. Gut inflammation and enteric disease triggered >55% lysogenic conversion of ATCC14028S within 3 days. Without inflammation, SopEΦ transfer was reduced by up to 10-fold. This was because inflammation (e.g., reactive oxygen species, reactive nitrogen species, hypochlorite) triggers the bacterial SOS response, boosts expression of the phage antirepressor Tum, and thereby promotes free phage production and subsequent transfer. Mucosal vaccination prevented a dense intestinal Tm population from inducing inflammation and consequently abolished SopEΦ transfer. Vaccination may be a general strategy for blocking pathogen evolution that requires disease-driven transfer of temperate bacteriophages.
噬菌体转移（溶原性转换）促进了细菌毒力的进化。对于决定感染宿主中溶原性转换动力学的因素，我们的了解还很有限。本研究使用鼠伤寒沙门氏菌（Tm）腹泻模型来研究 SopEΦ（来自 Tm SL1344 的噬菌体）向 Tm ATCC14028S 的转移。肠道炎症和肠道疾病在 3 天内引发了 ATCC14028S 超过 55%的溶原性转换。没有炎症时，SopEΦ的转移减少了多达 10 倍。这是因为炎症（例如，活性氧、活性氮、次氯酸盐）会引发细菌 SOS 反应，增强噬菌体抗阻遏物 Tum 的表达，从而促进游离噬菌体的产生和随后的转移。黏膜疫苗接种可防止密集的肠道 Tm 种群引发炎症，从而阻止 SopEΦ的转移。疫苗接种可能是阻止需要疾病驱动的温和噬菌体转移的病原体进化的一种通用策略。
