Resistance to leukocytes ties benefits of quorum sensing dysfunctionality to biofilm infection

被引:62
作者
He, Lei [1 ,2 ]
Le, Katherine Y. [1 ,3 ]
Khan, Burhan A. [1 ,5 ]
Thuan H Nguyen [1 ]
Hunt, Rachelle L. [1 ]
Bae, Justin S. [1 ]
Kabat, Juraj [4 ]
Zheng, Yue [1 ]
Cheung, Gordon Y. C. [1 ]
Li, Min [2 ]
Otto, Michael [1 ]
机构
[1] NIAID, Pathogen Mol Genet Sect, Lab Bacteriol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[2] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Lab Med, Shanghai, Peoples R China
[3] Mayo Clin, Coll Med, Dept Med, Div Hosp Internal Med, Rochester, MN USA
[4] NIAID, Biol Imaging Sect, Res Technol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[5] Univ Queensland, Diamantina Inst, Translat Res Inst, Woolloongabba, Qld, Australia
基金
美国国家卫生研究院; 中国国家自然科学基金;
关键词
STAPHYLOCOCCUS-AUREUS; AGR DYSFUNCTION; IMMUNE EVASION; VIRULENCE; EVOLUTION; DETERMINANTS; MECHANISMS; MATURATION; STRATEGIES; PEPTIDES;
D O I
10.1038/s41564-019-0413-x
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Social interactions play an increasingly recognized key role in bacterial physiology(1). One of the best studied is quorum sensing (QS), a mechanism by which bacteria sense and respond to the status of cell density(2). 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(3). QS mutants are also often isolated from biofilm-associated infections, including cystic fibrosis lung infection(4), as well as medical device infection and associated bacteraemia(5-7). However, despite the frequently proposed use of QS blockers to control virulence(8), 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.
引用
收藏
页码:1114 / 1119
页数:6
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