CDK1‑induced regulation of p53 phosphorylation at Ser315 mediates cell cycle arrest and apoptosis of macrophages infected with clinical isolates of <i>Mycobacterium tuberculosis</i>

Tuberculosis (TB) is an infectious disease caused by infection with <i>Mycobacterium tuberculosis</i> (MTB). The morbidity of TB in the Xinjiang region of China is higher than that in other provinces. Macrophage apoptosis after infection with MTB is considered to serve a key role in killing the bacteria. However, the biological process of apoptosis and the underlying molecular mechanisms triggered by the infection of macrophages with clinical isolates of MTB from Xinjiang (XJMTB) are not clear. The present study aimed to investigate the unique characteristics of XJMTB. Briefly, western blotting and flow cytometry were employed in the present study, and it was demonstrated that macrophages infected with MTB H37Rv or XJMTB underwent G2/M cell cycle arrest and apoptosis. The transcriptome sequencing analysis showed that cyclin‑dependent kinase 1 (CDK1) was a key regulatory gene in regulating the G2/M cell cycle arrest and apoptosis in MTB‑infected macrophages, and the p53 gene was most likely involved in the regulation of this. Moreover, the phosphorylation of p53 (Ser315) was elevated with the upregulation of CDK1 activation, leading to a higher proportion of MTB‑infected macrophages exhibiting G2/M cell cycle block and apoptosis. The current study also revealed that enhanced activation of CDK1 reversed the attenuation of the G2/M cell cycle block and the reduction in the percentage of apoptosis caused by inhibition of p53 (Ser315) phosphorylation. Furthermore, the co‑immunoprecipitation experiment demonstrated an interaction between CDK1 and p53. The present study indicated that, in an <i>in vitro</i> model of macrophage infection with XJMTB, enhanced activation of CDK1 may regulate the phosphorylation of p53 (Ser315), promote the secretion of TNF‑α, IL‑6, IL‑10, IL‑1β and IL‑12, promote G2/M cell cycle arrest and apoptosis of macrophages, and enhance the survival of XJMTB in macrophages. These results provide CDK1 and phosphorylated‑p53 as two new potential therapeutic targets for TB in Xinjiang, and lay a foundation for the development of novel TB treatment strategies.