Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA, USA.
mBio. 2012 Jun 12;3(3). doi: 10.1128/mBio.00143-12. Print 2012.
Information on how emerging pathogens can invade and persist and spread within host populations remains sparse. In the 1980s, a multidrug-resistant Salmonella enterica serotype Typhimurium clone lysogenized by a bacteriophage carrying the sopE virulence gene caused an epidemic among cattle and humans in Europe. Here we show that phage-mediated horizontal transfer of the sopE gene enhances the production of host-derived nitrate, an energetically highly valuable electron acceptor, in a mouse colitis model. In turn, nitrate fuels a bloom of S. Typhimurium in the gut lumen through anaerobic nitrate respiration while suppressing genes for the utilization of energetically inferior electron acceptors such as tetrathionate. Through this mechanism, horizontal transfer of sopE can enhance the fitness of S. Typhimurium, resulting in its significantly increased abundance in the feces. IMPORTANCE During gastroenteritis, Salmonella enterica serotype Typhimurium can use tetrathionate respiration to edge out competing microbes in the gut lumen. However, the concept that tetrathionate respiration confers a growth benefit in the inflamed gut is not broadly applicable to other host-pathogen combinations because tetrathionate respiration is a signature trait used to differentiate Salmonella serotypes from most other members of the family Enterobacteriaceae. Here we show that by acquiring the phage-carried sopE gene, S. Typhimurium can drive the host to generate an additional respiratory electron acceptor, nitrate. Nitrate suppresses genes for the utilization of energetically inferior electron acceptors such as tetrathionate while enhancing the luminal growth of S. Typhimurium through anaerobic nitrate respiration. Pathways for anaerobic nitrate respiration are widely conserved among members of the family Enterobacteriaceae, thereby making our observations relevant to other enteric pathogens whose relative abundance in the intestinal lumen increases during infection.
有关新出现的病原体如何入侵、持续存在和在宿主群体中传播的信息仍然很少。20 世纪 80 年代，一种由携带 sopE 毒力基因噬菌体溶原化的多重耐药性鼠伤寒沙门氏菌血清型 Typhimurium 克隆在欧洲引起了牛和人类的流行。在这里，我们表明，噬菌体介导的 sopE 基因的水平转移增强了宿主衍生硝酸盐的产生，硝酸盐是一种能量非常有价值的电子受体，在小鼠结肠炎模型中。反过来，硝酸盐通过厌氧硝酸盐呼吸为鼠伤寒沙门氏菌在肠道腔中的大量繁殖提供燃料，同时抑制了利用能量较低的电子受体（如连四硫酸盐）的基因。通过这种机制，sopE 的水平转移可以增强鼠伤寒沙门氏菌的适应性，导致其在粪便中的丰度显著增加。
在肠胃炎期间，鼠伤寒沙门氏菌可以利用连四硫酸盐呼吸来排挤肠道腔中的竞争微生物。然而，连四硫酸盐呼吸在炎症肠道中赋予生长优势的概念并不广泛适用于其他宿主-病原体组合，因为连四硫酸盐呼吸是一种用于区分沙门氏菌血清型与肠杆菌科大多数其他成员的特征性特征。在这里，我们表明，通过获得噬菌体携带的 sopE 基因，鼠伤寒沙门氏菌可以促使宿主产生另一种呼吸电子受体硝酸盐。硝酸盐抑制了利用能量较低的电子受体（如连四硫酸盐）的基因，同时通过厌氧硝酸盐呼吸增强了鼠伤寒沙门氏菌在腔中的生长。肠杆菌科成员中广泛保守的厌氧硝酸盐呼吸途径，使我们的观察结果与其他肠道病原体相关，这些病原体在感染期间其在肠道腔中的相对丰度增加。
