Staphylococcus Aureus Autoinducer-2Quorum Sensing Decreases Biofilm Formation In An IcaR-dependent Manner

Staphylococcus aureus is an important pathogen that causes biofilm-associated infection in humans. Autoinducer2(AI-2), a quorum-sensing (QS) signal for interspecies communication, has a wide range of regulatory functions in both Gram-positive and Gram-negative bacteria, but its exact role in biofilm formation in S. aureus remains unclear. Here we demonstrate that mutation of the AI-2synthase gene luxS in S. aureus RN6390B results in increased biofilm formation compared with the wild-type (WT) strain under static, flowing and anaerobic conditions and in a mouse model. Addition of the chemically synthesized AI-2precursor in the luxS mutation strain (AluxS) restored the WT phenotype. Real-time RT-PCR analysis showed that AI-2activated the transcription of icaR, a repressor of the ica operon, and subsequently a decreased level of icaA transcription, which was presumably the main reason why luxS mutation influences biofilm formation. Furthermore, we compared the roles of the agr-mediated QS system and the LuxS/AI-2QS system in the regulation of biofilm formation using the ΔluxS strain, RN6911and the Aagr AluxS strain. Our data indicate a cumulative effect of the two QS systems on the regulation of biofilm formation in S. aureus. These findings demonstrate that AI-2can decrease biofilm formation in S. aureus via an icaR-activation pathway. This study may provide clues for therapy in S. aureus biofilm-associated infection.