novel inhibitors of staphylococcus aureus virulence gene expression and biofilm formation新型抑制剂的金黄色葡萄球菌毒力基因表达和生物膜的形成.pdfVIP

Novel Inhibitors of Staphylococcus aureus Virulence Gene Expression and Biofilm Formation 1 1 2 2 3 2 Yibao Ma , Yuanxi Xu , Bryan D. Yestrepsky , Roderick J. Sorenson , Meng Chen , Scott D. Larsen *, Hongmin Sun1* 1 Department of Internal Medicine, University of Missouri, Columbia, Missouri, United States of America, 2 Vahlteich Medicinal Chemistry Core, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, United States of America, 3 Nanova, Inc., Columbia, Missouri, United States of America Abstract Staphylococcus aureus is a major human pathogen and one of the more prominent pathogens causing biofilm related infections in clinic. Antibiotic resistance in S. aureus such as methicillin resistance is approaching an epidemic level. Antibiotic resistance is widespread among major human pathogens and poses a serious problem for public health. Conventional antibiotics are either bacteriostatic or bacteriocidal, leading to strong selection for antibiotic resistant pathogens. An alternative approach of inhibiting pathogen virulence without inhibiting bacterial growth may minimize the selection pressure for resistance. In previous studies, we identified a chemical series of low molecular weight compounds capable of inhibiting group A streptococcus virulence following this alternative anti-microbial approach. In the current study, we demonstrated that two analogs of this class of novel anti-virulence compounds also inhibited virulence gene expression of S. aureus and exhibited an inhibitory effect on S. aureus biofilm formation. This class of