Social interactions play an increasingly recognized key role in bacterial physiology1. One of the best studied is quorum sensing (QS), a mechanism by which bacteria sense and respond to the status of cell density2. 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 community3. QS mutants are also often isolated from biofilm-associated infections, including cystic fibrosis lung infection4, as well as medical device infection and associated bacteraemia5,6,7. However, despite the frequently proposed use of QS blockers to control virulence8, 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.
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All data generated or analysed during this study are included in this published article (and its supplementary information files) or available from the corresponding author upon request.
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This study was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), U.S. National Institutes of Health (NIH) (project no. 1 ZIA AI000904) to M.O., The National Natural Science Foundation of China (grant no. 81501804) to L.H. and the General Program of Shanghai Municipal Commission of Health and Family Planning (grant no. 20154Y0014) to L.H.
The authors declare no competing interests.
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He, L., Le, K.Y., Khan, B.A. et al. Resistance to leukocytes ties benefits of quorum sensing dysfunctionality to biofilm infection. Nat Microbiol 4, 1114–1119 (2019). https://doi.org/10.1038/s41564-019-0413-x
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