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Impact of sdhCAB operon of Staphylococcus aureus on persister formation |
WANG Xuyang, CHEN Gang, WANG Shiyong, WANG Wenjie, CHEN Jiazhen, ZHANG Wenhong |
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China |
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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.
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Received: 07 May 2018
Published: 25 October 2018
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Corresponding Authors:
CHEN Jiazhen
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