Absence of Protoheme IX Farnesyltransferase CtaB Causes Virulence Attenuation but Enhances Pigment Production and Persister Survival in MRSA.
The membrane protein CtaB inS. aureusis a protoheme IX farnesyltransferase involved in the synthesis of the heme containing terminal oxidases of bacterial respiratory chain. In this study, to assess the role of CtaB inS. aureusvirulence, pigment production, and persister formation, we constructed actaBmutant in the methicillin-resistantStaphylococcus aureus(MRSA) strain USA500. We found that deletion ofctaBattenuated growth and virulence in mice but enhanced pigment production and formation of quinolone tolerant persister cells in stationary phase. RNA-seq analysis showed that deletion ofctaBcaused decreased transcription of several virulence genes including RNAIII which is consistent with its virulence attenuation. In addition, transcription of 20 ribosomal genes and 24 genes involved in amino acid biosynthesis was significantly down-regulated in thectaBknockout mutant compared with the parent strain. These findings suggest the importance of heme biosynthesis in virulence and persister formation ofS. aureus.
Key Laboratory of Medical Molecular Virology, Huashan Hospital, Shanghai Medical College of Fudan University Shanghai, China.
Tao
T
Xu
Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University Lanzhou, China.
Jian
J
Han
Key Laboratory of Medical Molecular Virology, Huashan Hospital, Shanghai Medical College of Fudan University Shanghai, China.
Jia
J
Zhang
Key Laboratory of Medical Molecular Virology, Huashan Hospital, Shanghai Medical College of Fudan University Shanghai, China.
Jiazhen
J
Chen
Key Laboratory of Medical Molecular Virology, Huashan Hospital, Shanghai Medical College of Fudan University Shanghai, China.
Nan
N
Wu
Key Laboratory of Medical Molecular Virology, Huashan Hospital, Shanghai Medical College of Fudan University Shanghai, China.
Wenhong
W
Zhang
Key Laboratory of Medical Molecular Virology, Huashan Hospital, Shanghai Medical College of Fudan UniversityShanghai, China; Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins UniversityBaltimore, MD, USA.
Ying
Y
Zhang
Staphylococcus aureus; antibiotics; heme; persister formation; pigment; virulence