Factors that Influence Colonization with Staphylococcus aureus: The Role of Triclosan, the Immune Response, and Polymicrobial Interactions

[摘要] Staphylococcus aureus is an opportunistic pathogen that colonizes about 30% of the human population. While S. aureus normally colonizes the host without causing disease, it can become a deadly pathogen responsible for more than 19,000 deaths annually in the United States. Colonization with S. aureus increases the risk of getting a post-operative infection. Since we have limited options for antibiotic treatment of S. aureus infections, the need to understand S. aureus colonization factors is important. Environmental factors, interplay with the host, and polymicrobial interactions can all influence the ability of S. aureus to persist on human skin and incorporate into the microbial flora. First I show that the environmental contaminant triclosan, a common biocide used in consumer products, is able to promote S. aureus nasal colonization. Furthermore, triclsoan can induce surface attachment and biofilm formation of S. aureus and the clinically significant pathogens Escherichia coli and Pseudomonas aeruginosa. Second, I characterize the S. aureus phenol soluble modulin (PSM) proteins as necessary and sufficient for the lytic release of proinflammatory molecules from human keratinocytes. Additionally, PSMs are required for the induction of skin inflammation in a murine model of atopic dermatitis. Lastly, I characterize the ability of S. aureus to hitchhike on Brevibacillus and promote Brevibacillus motility using PSM surfactants. Hitchhiking is a novel method of motility for non-motile bacteria. The three projects presented here provide novel insight into how S. aureus colonizes the human host. Though understanding environmental, human, and polymicrobial factors, we can begin to investigate novel targets for S. aureus decolonization therapy.

[发布机构] University of Michigan

[效力级别] Phenol soluble modulins (PSMs) release proinflammatory cytokines from skin

[关键词] Triclosan promotes nasal colonization with S. aureus;Phenol soluble modulins (PSMs) release proinflammatory cytokines from skin;S. aureus hitchhikes on Brevibacillus and promotes motility;Molecular;Cellular and Developmental Biology;Science;Molecular, Cellular and Developmental Biology