Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MD, USA.
Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Nat Microbiol. 2019 Jul;4(7):1114-1119. doi: 10.1038/s41564-019-0413-x. Epub 2019 Apr 1.
Social interactions play an increasingly recognized key role in bacterial physiology. One of the best studied is quorum sensing (QS), a mechanism by which bacteria sense and respond to the status of cell density. While QS is generally deemed crucial for bacterial survival, QS-dysfunctional mutants frequently arise in in vitro culture. This has been explained by the fitness cost an individual mutant, a 'quorum cheater', saves at the expense of the community. QS mutants are also often isolated from biofilm-associated infections, including cystic fibrosis lung infection, as well as medical device infection and associated bacteraemia. However, despite the frequently proposed use of QS blockers to control virulence, the mechanisms underlying QS dysfunctionality during infection have remained poorly understood. Here, we show that in the major human pathogen Staphylococcus aureus, quorum cheaters arise exclusively in biofilm infection, while in non-biofilm-associated infection there is a high selective pressure to maintain QS control. We demonstrate that this infection-type dependence is due to QS-dysfunctional bacteria having a significant survival advantage in biofilm infection because they form dense and enlarged biofilms that provide resistance to phagocyte attacks. Our results link the benefit of QS-dysfunctional mutants in vivo to biofilm-mediated immune evasion, thus to mechanisms that are specific to the in vivo setting. Our findings explain why QS mutants are frequently isolated from biofilm-associated infections and provide guidance for the therapeutic application of QS blockers.
社交互动在细菌生理学中起着越来越被认可的关键作用。其中研究最多的是群体感应 (QS)，这是一种细菌感知和响应细胞密度状态的机制。虽然 QS 通常被认为对细菌的生存至关重要，但在体外培养中，QS 功能失调的突变体经常出现。这可以解释为个体突变体（“群体欺骗者”）节省的适应度成本，是以群体为代价的。QS 突变体也经常从生物膜相关感染中分离出来，包括囊性纤维化肺部感染，以及医疗器械感染和相关菌血症。然而，尽管经常提出使用 QS 阻断剂来控制毒力，但感染期间 QS 功能失调的机制仍知之甚少。在这里，我们表明在主要的人类病原体金黄色葡萄球菌中，群体欺骗者仅在生物膜感染中出现，而在非生物膜相关感染中，维持 QS 控制的选择性压力很大。我们证明这种感染类型的依赖性是由于 QS 功能失调的细菌在生物膜感染中具有显著的生存优势，因为它们形成密集和扩大的生物膜，提供了对吞噬细胞攻击的抵抗力。我们的结果将 QS 功能失调突变体在体内的益处与生物膜介导的免疫逃避联系起来，从而与体内特定的机制联系起来。我们的发现解释了为什么 QS 突变体经常从生物膜相关感染中分离出来，并为 QS 阻断剂的治疗应用提供了指导。
