Han Jian, He Lili, Shi Wanliang, Xu Xiaogang, Wang Sen, Zhang Shuo, Zhang Ying
Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China; Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
PLoS One. 2014 Sep 24;9(9):e108325. doi: 10.1371/journal.pone.0108325. eCollection 2014.
S. aureus is a significant human pathogen and has previously been shown to form cell wall deficient forms or L-forms in vitro and in vivo during infection. Despite many previous studies on S. aureus L-forms, the mechanisms of L-form formation in this organism remain unknown. Here we established the L-form model in S. aureus and constructed a transposon mutant library to identify genes involved in L-form formation. Screening of the library for mutants defective in L-form formation identified glpF involved in glycerol uptake being important for L-form formation in S. aureus. Consistent with this observation, glpF was found to be highly expressed in L-form S. aureus but hardly expressed in normal walled form. In addition, glpF mutant was found to be defective in antibiotic persistence. The defect in L-form formation and antibiotic persistence of the glpF mutant could be complemented by the wild type glpF gene. These findings provide new insight into the mechanisms of L-form formation and persistence in S. aureus and may have implications for development of new drugs targeting persisters for improved treatment.
金黄色葡萄球菌是一种重要的人类病原体，先前已证明它在体外和体内感染过程中会形成细胞壁缺陷型，即L型。尽管此前对金黄色葡萄球菌L型进行了许多研究，但该生物体中L型形成的机制仍不清楚。在此，我们建立了金黄色葡萄球菌的L型模型，并构建了一个转座子突变体文库，以鉴定参与L型形成的基因。对该文库进行筛选，寻找L型形成有缺陷的突变体，结果确定参与甘油摄取的glpF对金黄色葡萄球菌的L型形成很重要。与这一观察结果一致，发现glpF在L型金黄色葡萄球菌中高表达，但在正常细胞壁形式中几乎不表达。此外，发现glpF突变体在抗生素耐受性方面存在缺陷。glpF突变体在L型形成和抗生素耐受性方面的缺陷可由野生型glpF基因互补。这些发现为金黄色葡萄球菌中L型形成和耐受性的机制提供了新的见解，可能对开发针对耐受性细菌的新型药物以改善治疗有启示意义。
