Liu Cui Hua, Lee S Melanie, Vanlare Jordan M, Kasper Dennis L, Mazmanian Sarkis K
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3951-6. doi: 10.1073/pnas.0709266105. Epub 2008 Mar 4.
Microbes occupy countless ecological niches in nature. Sometimes these environments may be on or within another organism, as is the case in both microbial infections and symbiosis of mammals. Unlike pathogens that establish opportunistic infections, hundreds of human commensal bacterial species establish a lifelong cohabitation with their hosts. Although many virulence factors of infectious bacteria have been described, the molecular mechanisms used during beneficial host-symbiont colonization remain almost entirely unknown. The novel identification of multiple surface polysaccharides in the important human symbiont Bacteroides fragilis raised the critical question of how these molecules contribute to commensalism. To understand the function of the bacterial capsule during symbiotic colonization of mammals, we generated B. fragilis strains deleted in the global regulator of polysaccharide expression and isolated mutants with defects in capsule expression. Surprisingly, attempts to completely eliminate capsule production are not tolerated by the microorganism, which displays growth deficits and subsequent reversion to express capsular polysaccharides. We identify an alternative pathway by which B. fragilis is able to reestablish capsule production and modulate expression of surface structures. Most importantly, mutants expressing single, defined surface polysaccharides are defective for intestinal colonization compared with bacteria expressing a complete polysaccharide repertoire. Restoring the expression of multiple capsular polysaccharides rescues the inability of mutants to compete for commensalism. These findings suggest a model whereby display of multiple capsular polysaccharides provides essential functions for bacterial colonization during host-symbiont mutualism.
微生物在自然界中占据着无数的生态位。有时这些环境可能存在于另一种生物体之上或体内，哺乳动物的微生物感染和共生情况皆是如此。与引发机会性感染的病原体不同，数百种人类共生细菌物种与宿主建立了终身共存关系。尽管已经描述了许多传染性细菌的毒力因子，但有益的宿主 - 共生体定殖过程中所使用的分子机制几乎完全未知。在重要的人类共生菌脆弱拟杆菌中首次鉴定出多种表面多糖，这引发了一个关键问题，即这些分子如何促进共生关系。为了了解哺乳动物共生定殖过程中细菌荚膜的功能，我们构建了在多糖表达全局调节因子中缺失的脆弱拟杆菌菌株，并分离出荚膜表达存在缺陷的突变体。令人惊讶的是，微生物无法耐受完全消除荚膜产生的尝试，这表现为生长缺陷以及随后恢复表达荚膜多糖。我们确定了一条替代途径，通过该途径脆弱拟杆菌能够重新建立荚膜产生并调节表面结构的表达。最重要的是，与表达完整多糖库的细菌相比，表达单一、特定表面多糖 的突变体在肠道定殖方面存在缺陷。恢复多种荚膜多糖的表达可挽救突变体在共生竞争中的无能。这些发现提出了一个模型，即多种荚膜多糖的展示为宿主 - 共生体共生过程中的细菌定殖提供了基本功能。
