Mashruwala Ameya A, Gries Casey M, Scherr Tyler D, Kielian Tammy, Boyd Jeffrey M
Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, New Jersey, USA.
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Infect Immun. 2017 Jul 19;85(8). doi: 10.1128/IAI.00157-17. Print 2017 Aug.
Biofilms are multicellular communities of microorganisms living as a quorum rather than as individual cells. The bacterial human pathogen uses oxygen as a terminal electron acceptor during respiration. Infected human tissues are hypoxic or anoxic. We recently reported that impaired respiration elicits a rogrammed ell ysis (PCL) phenomenon in leading to the release of cellular polymers that are utilized to form biofilms. PCL is dependent upon the AtlA murein hydrolase and is regulated, in part, by the SrrAB two-component regulatory system (TCRS). In the current study, we report that the SaeRS TCRS also governs fermentative biofilm formation by positively influencing AtlA activity. The SaeRS-modulated factor fibronectin-binding protein A (FnBPA) also contributed to the fermentative biofilm formation phenotype. SaeRS-dependent biofilm formation occurred in response to changes in cellular respiratory status. Genetic evidence presented suggests that a high cellular titer of phosphorylated SaeR is required for biofilm formation. Epistasis analyses found that SaeRS and SrrAB influence biofilm formation independently of one another. Analyses using a mouse model of orthopedic implant-associated biofilm formation found that both SaeRS and SrrAB govern host colonization. Of these two TCRSs, SrrAB was the dominant system driving biofilm formation We propose a model wherein impaired cellular respiration stimulates SaeRS via an as yet undefined signal molecule(s), resulting in increasing expression of AtlA and FnBPA and biofilm formation.
生物膜是微生物的多细胞群落，它们以群体感应的方式生活，而不是单个细胞。这种人类细菌性病原体在呼吸过程中使用氧气作为终端电子受体。受感染的人体组织处于缺氧或无氧状态。我们最近报道，呼吸功能受损会引发程序性细胞裂解（PCL）现象，导致细胞聚合物的释放，这些聚合物被用于形成生物膜。PCL依赖于AtlA胞壁质水解酶，部分受SrrAB双组分调节系统（TCRS）调控。在本研究中，我们报道SaeRS TCRS也通过正向影响AtlA活性来控制发酵性生物膜的形成。SaeRS调节因子纤连蛋白结合蛋白A（FnBPA）也有助于发酵性生物膜形成表型。SaeRS依赖的生物膜形成是对细胞呼吸状态变化的响应。所提供的遗传学证据表明，生物膜形成需要高细胞滴度的磷酸化SaeR。上位性分析发现，SaeRS和SrrAB彼此独立地影响生物膜形成。使用骨科植入物相关生物膜形成小鼠模型的分析发现，SaeRS和SrrAB都控制宿主定殖。在这两个TCRS中，SrrAB是驱动生物膜形成的主要系统。我们提出一个模型，其中细胞呼吸受损通过一种尚未确定的信号分子刺激SaeRS，导致AtlA和FnBPA表达增加以及生物膜形成。
