Opportunistic bacterial pathogens must compete with other bacteria and switch between host- and environment-adapted states. Type VI secretion systems (T6SSs) occur widely in gram-negative bacteria and can efficiently kill neighboring competitors. We determined the distribution of T6SSs across the genus Serratia and observed that a highly conserved antibacterial T6SS is differentially active between closely related clinical isolates of Serratia marcescens. By combining genomic and experimental approaches, we identified a genus-core two-component system, BetR-Reg1-Reg2, that controls T6SS activity and exhibits frequent inactivating mutations, exclusively in S. marcescens isolates of clinical origin. This regulatory system controls a number of lifestyle-related traits at transcriptional and post-translational levels, including T6SS activity, antibiotic production, motility, and adhesion, with loss of BetR increasing virulence in an in vivo infection model. Our data support a model whereby this system represents a conserved, modular switch from sessile to pioneering and aggressive behavior, which is subject to selection pressure in clinical environments.

中文翻译：

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粘质沙雷氏菌的竞争行为受到一种生活方式转变的协调调节，这种转变在临床环境中经常失活


机会性细菌病原体必须与其他细菌竞争，并在宿主和环境适应状态之间切换。VI 型分泌系统 （T6SSs） 广泛存在于革兰氏阴性菌中，可以有效地杀死邻近的竞争者。我们确定了 T6SSs 在沙雷氏菌属中的分布，并观察到高度保守的抗菌 T6SS 在粘质沙雷氏菌密切相关的临床分离株之间具有不同的活性。通过结合基因组学和实验方法，我们确定了一种属核心双组分系统 BetR-Reg1-Reg2，该系统控制 T6SS 活性并表现出频繁的失活突变，仅在临床来源的粘质链球菌 分离株中。该调节系统在转录和翻译后水平控制许多与生活方式相关的性状，包括 T6SS 活性、抗生素产生、运动和粘附，在体内感染模型中，BetR 的缺失会增加毒力 。我们的数据支持一个模型，该系统代表了从固座行为到开拓性和攻击性行为的保守、模块化转变，这在临床环境中受到选择压力的影响。