Institute for Infectiology, Center for Molecular Biology of Inflammation, University of Münster, Münster, Germany.
Institute for Infectiology, Center for Molecular Biology of Inflammation, University of Münster, Münster, Germany.
J Mol Biol. 2019 Nov 22;431(23):4645-4655. doi: 10.1016/j.jmb.2019.06.024. Epub 2019 Jun 28.
Recent studies revealed an amazing phenotypic heterogeneity between genetically identical individual cells within populations of microbial pathogens. During the course of an infection, subpopulations occur, which differ in certain virulence-relevant factors, stress adaptation functions or physiological and metabolic abilities. The mechanisms driving this heterogeneity are divergent reactions of the pathogens to differences in host tissue microenvironments. In addition, certain genetic regulatory circuits with positive feedback loops and stochastic differences in gene expression can generate endogenous fluctuations in regulatory components leading to bistable expression of virulence-associated functions. Here, we focus on the occurrence of phenotypic heterogeneity in populations of well-studied examples of pathogens, which enables cooperative, social behavior where a subpopulation of producers shares fitness- and/or virulence-relevant goods and traits with non-producers. We further highlight that this strategy allows preadaptation of a subgroup of cells to recurrent and thus predictable changes of the environment that they encounter during the different stages of the infection. The diversity within bacterial communities has a significant influence on the survival of the pathogens within their hosts and the progression of the disease.
最近的研究揭示了在微生物病原体群体中，遗传上相同的个体细胞之间存在惊人的表型异质性。在感染过程中，会出现亚群，它们在某些与毒力相关的因素、应激适应功能或生理和代谢能力上存在差异。导致这种异质性的机制是病原体对宿主组织微环境差异的不同反应。此外，具有正反馈回路的某些遗传调控回路和基因表达的随机差异会导致调控成分的内源性波动，从而导致与毒力相关功能的双稳态表达。在这里，我们重点关注在经过充分研究的病原体的种群中出现的表型异质性，这种异质性使群体中的一部分生产者能够与非生产者分享与适应性和/或毒力相关的物质和特征，从而实现合作、社交行为。我们进一步强调，这种策略允许细胞亚群对它们在感染的不同阶段遇到的环境的反复且可预测的变化进行预先适应。细菌群落内的多样性对病原体在宿主中的生存和疾病的进展有重大影响。
