Basic Processes in Salmonella-Host Interactions: Within-Host Evolution and the Transmission of the Virulent Genotype
Basic Processes in Salmonella-Host Interactions: Within-Host Evolution and the Transmission of the Virulent Genotype
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DOI：
10.1128/microbiolspec.mtbp-0012-2016
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发表时间：
2017-10-01
影响因子：
3.7
通讯作者：
Hardt, Wolf-Dietrich
中科院分区：
文献类型：
--
作者：
Diard, Mederic;Hardt, Wolf-Dietrich
传播和毒力是病原体进化的核心方面。然而，在许多情况下，它们的相互联系已证明难以通过实验来评估。在这里，我们讨论了沙门氏菌腹泻小鼠模型的最新进展。小鼠模型模拟了抗生素治疗个体对非伤寒沙门氏菌病的增强敏感性。在链霉素预处理的小鼠中，肠道沙门氏菌亚种1血清型鼠伤寒沙门氏菌有效地定殖在肠道内并引起明显的肠病。在宿主的肠道中，鼠伤寒沙门氏菌形成两个亚群，它们合作引发疾病并优化传播。致病亚群表达一组专门的毒力因子（3型分泌系统1 [TTSS-1]），驱动肠道组织侵袭。毒力因子的表达是“昂贵的”，因为它延缓了生长速度，并使病原体暴露于肠道组织内的先天免疫防御。这些代价由入侵亚群引起的肠道炎症（一种“公共产品”）来补偿。发炎的肠腔促进鼠伤寒沙门氏菌的生长，特别是TTSS-1“关闭”亚群的生长。后者生长到非常高的密度并促进传播。因此，这两种表型合作引发疾病并确保传播。该系统为研究病原体毒力在宿主内的进化、协同毒力如何稳定以及环境变化（如抗生素治疗）如何影响毒力基因型的传播提供了实验框架。
Transmission and virulence are central aspects of pathogen evolution. However, in many cases their interconnection has proven difficult to assess by experimentation. Here we discuss recent advances from a mouse model for Salmonella diarrhea. Mouse models mimic the enhanced susceptibility of antibiotic-treated individuals to nontyphoidal salmonellosis. In streptomycin-pretreated mice, Salmonella enterica subspecies 1 serovar Typhimurium efficiently colonizes the gut lumen and elicits pronounced enteropathy. In the host's gut, S. Typhimurium forms two subpopulations that cooperate to elicit disease and optimize transmission. The disease-causing subpopulation expresses a set of dedicated virulence factors (the type 3 secretion system 1 [TTSS-1]) that drive gut tissue invasion. The virulence factor expression is "costly" by retarding the growth rate and exposing the pathogen to innate immune defenses within the gut tissue. These costs are compensated by the gut inflammation (a "public good") that is induced by the invading subpopulation. The inflamed gut lumen fuels S. Typhimurium growth, in particular that of the TTSS-1 "off" subpopulation. The latter grows up to very high densities and promotes transmission. Thus, both phenotypes cooperate to elicit disease and ensure transmission. This system has provided an experimental framework for studying within-host evolution of pathogen virulence, how cooperative virulence is stabilized, and how environmental changes (e.g., antibiotic therapy) affect the transmission of the virulent genotype.