Abstract:Persisters are a small portion of bacteria insensitive to lethal dose of antibiotic treatment and are important cause for chronic infections. Staphylococcus aureus (S. aureus) is an important pathogen causing acute and chronic clinical infections. Although sdhCAB operon of S. aureus had been implicated in persister formation, the impact of sdhCAB operon knockout is still missing. In this study, we demonstrated that knockout of sdhCAB operon in USA500 had a significantly negative impact on its persister formation on the stress of acid, oxidation, and antibiotic treatment. The impact was reversed by gene complementation. RNA sequencing (RNA-seq) analysis showed that deletion of sdhCAB decreased the expression of genes involved in drug resistance, amino acid and carbohydrate metabolism, porphyrin metabolism, and transporters and increased the expression of genes of methane metabolism pathway, tricarboxylic acid cycle, polymerase IV, etc. Quantitative real-time polymerase chain reaction (PCR) confirmed the transcription changes in 20 out of 23 genes. Phenotype microarray analysis (PM) showed that the knockout of sdhCAB operon could decrease the metabolism of 64 carbon sources, such as succinic acid, citric acid, glycogen, and L-aspartic acid, but the metabolism of various phosphate sources and nitrogen sources was not impacted. The results suggest that the sdhCAB operon affects persister formation through its impact on metabolism. The findings provide new insights for study and treatment of S. aureus persistent infections.
王旭阳,陈刚,王士勇,王文婕,陈嘉臻,张文宏. 金黄色葡萄球菌sdhCAB操纵子影响持留菌形成机制的研究[J]. 微生物与感染, 2018, 13(5): 284-298.
WANG Xuyang, CHEN Gang, WANG Shiyong, WANG Wenjie, CHEN Jiazhen, ZHANG Wenhong. Impact of sdhCAB operon of Staphylococcus aureus on persister formation. JOURNAL OF MICROBES AND INFECTIONS, 2018, 13(5): 284-298.