title: Glycerol uptake is important for L-form formation and persistence in Staphylococcus aureus.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jian
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors.forename: Lili
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Wanliang
authors.initials: W
authors.lastname: Shi
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Shuo
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America; Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015723:Gene Library; D005990:Glycerol / Q000378:metabolism*; D016254:Mutagenesis, Insertional; D009643:Norfloxacin / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D000667:Ampicillin; D009643:Norfloxacin; D005990:Glycerol