![]() The clemastine at 50 mM inhibited the biofilm formation of S. The discovery of this study identified novel use and mechanism of action of clemastine as a potential anti-biofilm drug for clinical application for S. aureus when used in combination with oxacillin by targeting the GdpP protein. aureus and enhanced antibacterial activity against S. In this study, clemastine, which is a histamine receptor H1 (HRH1) antagonist, was found to have a novel role of the significant inhibition against the biofilm formation and hemolytic activity of S. The novel anti-biofilm drug is urgently needed to address the looming crisis. aureus infections remains a serious challenge. Treatment failure of traditional antibiotics in biofilm-associated S. IMPORTANCE The biofilm formation, which protects bacteria from stresses, including antibiotics and host immune responses, can be commonly found in clinical S. Conclusively, clemastine might exert its inhibitory effects against the biofilm formation and hemolysis in S. Furthermore, the interaction between clemastine and GdpP protein was demonstrated by the molecular docking, gdpP overexpression experiment, and thermal stability assay. The genetic mutations on gdpP (cyclic di-AMP phosphodiesterase) were found in the clemastine-induced tolerant derivative isolate by whole-genome sequencing. The proteomics analysis of SA113 treated with clemastine demonstrated the significant changes in levels of biofilm-related proteins (stress response regulators ClpB and GroS, ATP-binding proteins, and urease metabolism), virulence-related proteins (SspA, superantigen, and VWbp), and methicillin resistance-related proteins (glutamine metabolism). aureus SA113 treated with clemastine displayed the decreased transcriptional level of the biofilm formation relevant genes (fnbB, icaA, and icaB), virulence genes (hlg, hld, lukde, lukpvl, beta-PSM, delta-PSM, and cap5A), and the regulatory genes agrA. Clemastine inhibited the release of eDNA during the biofilm formation and decreased the S. Moreover, the dramatic inhibition of biofilm formation was found in clinical S. Here, we demonstrated that clemastine showed slight bacteriostatic activity and enhanced the antibacterial activity of oxacillin against S. Thus, the development of novel antimicrobial agents capable to inhibit or eradicate S. aureus often results in chronic infection and the treatment tolerance toward the traditional antibiotics. In addition, recalcitrant biofilm formation of S. Staphylococcus aureus poses a significant threat to human health due to its virulence and multidrug resistance. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |