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

Abstract

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 bacteremia5–7. 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, QS-dysfunctional mutants 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. Notably, our findings explain why QS mutants are frequently isolated from biofilm-associated infections and provide guidance for the therapeutic application of QS blockers.