Inactivation of farR Causes High Rhodomyrtone Resistance and Increased Pathogenicity in Staphylococcus aureus.

摘要: Rhodomyrtone (Rom) is an acylphloroglucinol antibiotic originally isolated from leaves of Rhodomyrtus tomentosa. Rom targets the bacterial membrane and active against a wide range Gram-positive bacteria but exact mode action remains obscure. Here we characterized spontaneous Rom-resistant mutant model strain Staphylococcus aureus HG001 (RomR) to learn more about resistance mechanism. We showed that Rom-resistance based on single point mutation in coding region farR [regulator fatty acid (FA) resistance] causes amino change Cys Arg at position 116 FarR, affects FarR activity. Comparative transcriptome analysis revealed mutated transcription many genes distinct pathways. represses for example expression its own gene (farR), flanking farE (effector FA resistance), other global regulators such as agr sarA. All these were consequently upregulated RomR clone. Particularly upregulation sarA leads increased virulence rendering clone cytotoxic pathogenic mouse infection model. The largely due de-repression farE. FarE described efflux pump linoleic arachidonic acids. observed release lipids compared parental HG001. If deleted clone, or, if native expressed strain, corresponding strains become hypersensitive Rom. Overall, show here high mediated by overexpression important regulator, (RomR clone) makes hyper-virulent.