Abstract: Objective To investigate the influence of arginine metabolism on the virulence,pathogenicity and host physiology of Mycolicibacterium smegmatis（M. smeg）. Methods A M. smeg knockout isolate of argR was constructed. Wild-type M. smeg was used as control,and the growth ability of bacteria in vitro was determined. Real-time fluorescence quantitative polymerase chain reaction （RT-qPCR） was used to determine the expressions of fadD2,fadA5 and kstR. Epithelial cells A549 were infected with M. smeg. Cell activity was determined as well. UCP1 and DNM1L were determined by RT-qPCR. The physiological effect on host cells was observed. Results It was found that argR knockout increased the lipid storage capacity of bacteria and had a growth advantage in the medium with glucose as a single carbon source（P<0.001）. The synthesis of M. smeg mycoacid was up-regulated,and the virulence of epithelial cells A549 was increased. After the infection of epithelial cells A549 2 h,the cell entry rate was increased（P<0.001）,and the infection ability of epithelial cells A549 was improved. The deletion of argR affected cell viability by affecting its mitochondrial function. Conclusions The knockout of argR,a negative transcriptional regulator of arginine metabolism in M. smeg,enhances bacterial virulence and inhibits mitochondrial function in alveolar epithelial cells.

Key words: Mycolicibacterium smegmatis, A549, argR, Mitochondrion