Staphylococcus aureus enters viable-but-nonculturable state in response to chitooligosaccharide stress by altering metabolic pattern and transmembrane transport function

Although chitooligosaccharide (COS) has attracted the attention of some researchers due to its good solubility and broad-spectrum antibacterial activity, our study found that Staphylococcus aureus treated with low concentration of COS actively entered the viable-but-nonculturable (VBNC) state to resist this environmental stress. In this study, the transcriptome of VBNC-state S. aureus after COS treatment was analyzed by RNA-sequencing. Compared with the control group, pathway enrichment analysis showed that COS-treated S. aureus adopted a series of adaptive adjustment strategies for survival, including significant up-regulation of the differential genes' expression of such as ABC transporters (metI, tagG), Sec dependent transport pathway (secDF), peptidoglycan synthesis pathway (murG) and alteration of their physiological metabolic patterns, where ATP depletion played a key role in the formation of the VBNC-state S. aureus. Further, by using oxidative phosphorylation uncoupling agent to adjust the initial level of ATP in S. aureus, it was found that the reduction of intracellular ATP level could accelerate the formation of VBNC state. Overall, our results preliminarily elucidated the molecular mechanism of COS inducing the VBNC-state S. aureus. It provided an important theoretical reference for further achieving effective bacterial inactivation by COS.