Efflux Pump Mediated Streptococcus Mutans Resistance To Quaternary Ammonium Salt

The goals of this study were to explore the mechanisms of Streptococcus mutans (S. mutans) resistance to quaternary ammonium salt (QAS), dimethylaminohexadecyl methacrylate (DMAHDM). Drug-resistance of S. mutans UA 159 (S. mutans UA159-D) was induced with repeated exposures to DMAHDM. The morphological changes of S. mutans UA159-D were observed by transmission electron microscope (TEM). Membrane depolarization activity was determined with 3,3’-dipropylthiadicarbocyanine iodide [DiSC3(5)]. Prokaryotic transcriptome sequencing was used to analyse differentially expressed genes. Accordingly, efflux pump inhibitors were applied to verify the role of efflux pump in mediating DMAHDM-resistant. TEM showed that DMAHDM disrupted the membrane integrity of S. mutans UA159, but S. mutans UA159-D exhibited no obvious change in the same concentration of DMAHDM. The degree of membrane depolarization increased when S. mutans UA159 interacting with DMAHDM. However, S. mutans UA159-D showed less change in the degree of membrane depolarization. Transcriptome sequencing analysis showed different gene expression between S. mutans UA159-D and S. mutans UA159. The pathway analysis demonstrated the differentially expressed genes were mainly related to membrane transport. And most of these genes encode the efflux pump. Accordingly, addition of efflux pump inhibitors increased the minimal inhibitory concentration of S. mutans UA159-D to DMAHDM. The mechanisms of S. mutans resistance to QAS may related gene to efflux pump, stabilizing the membrane integrity and depolarization.