PDF(Pubmed)
Abstract：
Long-chain fatty acids with antimicrobial properties are abundant on the skin and mucosal surfaces, where they are essential to restrict the proliferation of opportunistic pathogens such as Staphylococcus aureus. These antimicrobial fatty acids (AFAs) elicit bacterial adaptation strategies, which have yet to be fully elucidated. Characterizing the pervasive mechanisms used by S. aureus to resist AFAs could open new avenues to prevent pathogen colonization. Here, we identify the S. aureus lipase Lip2 as a novel resistance factor against AFAs. Lip2 detoxifies AFAs via esterification with cholesterol. This is reminiscent of the activity of the fatty acid-modifying enzyme (FAME), whose identity has remained elusive for over three decades. In vitro, Lip2-dependent AFA-detoxification was apparent during planktonic growth and biofilm formation. Our genomic analysis revealed that prophage-mediated inactivation of Lip2 was rare in blood, nose, and skin strains, suggesting a particularly important role of Lip2 for host - microbe interactions. In a mouse model of S. aureus skin colonization, bacteria were protected from sapienic acid (a human-specific AFA) in a cholesterol- and lipase-dependent manner. These results suggest Lip2 is the long-sought FAME that exquisitely manipulates environmental lipids to promote bacterial growth in otherwise inhospitable niches.
摘要：
具有抗菌特性的长链脂肪酸在皮肤和粘膜表面丰富，它们对于限制机会性病原体如金黄色葡萄球菌的增殖至关重要。这些抗菌脂肪酸（AFA）引发细菌适应策略，尚未完全阐明。表征金黄色葡萄球菌用于抵抗AFA的普遍机制可以开辟防止病原体定植的新途径。这里,我们确定金黄色葡萄球菌脂肪酶Lip2是一种新型的抗AFAs因子。Lip2通过与胆固醇的酯化作用使AFAs解毒。这让人想起脂肪酸修饰酶（FAME）的活性，三十多年来，他的身份一直难以捉摸。体外，在浮游生长和生物膜形成过程中，依赖Lip2的AFA解毒作用很明显。我们的基因组分析显示，在血液中很罕见的是由前噬菌体介导的Lip2失活，鼻子,和皮肤菌株，这表明Lip2在宿主-微生物相互作用中起着特别重要的作用。在金黄色葡萄球菌皮肤定植的小鼠模型中，以胆固醇和脂肪酶依赖性方式保护细菌免受皂化酸（人类特异性AFA）的影响。这些结果表明，Lip2是长期寻求的FAME，可巧妙地操纵环境脂质以促进细菌在其他不适宜居住的生态位中的生长。
