Mycobacterium tuberculosis Fatty Acyl-CoA Synthetase fad D33 Promotes Bacillus Calmette-Guérin Survival in Hostile Extracellular and Intracellular Microenvironments in the Host.
Yifan ZhuHongling ShiTian TangQianqian LiYongchong PengLuiz E BermudezChangmin HuHuanchun ChenAizhen GuoYingyu ChenPublished in: Cells (2023)
Tuberculosis, caused by Mycobacterium tuberculosis ( M. tb ), remains a significant global health challenge. The survival of M. tb in hostile extracellular and intracellular microenvironments is crucial for its pathogenicity. In this study, we discovered a Bacillus Calmette-Guérin (BCG) mutant B1033 that potentially affected mycobacterium pathogenicity. This mutant contained an insertion mutation gene, fad D33, which is involved in lipid metabolism; however, its direct role in regulating M. tb infection is not well understood. Here, we found that the absence of fad D 33 reduced BCG adhesion and invasion into human pulmonary alveolar epithelial cells and increased the permeability of the mycobacterial cell wall, allowing M. tb to survive in the low pH and membrane pressure extracellular microenvironment of the host cells. The absence of fad D 33 also inhibited the survival of BCG in macrophages by promoting the release of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumors necrosis factor-α, through the mitogen-activated protein kinase p38 signaling pathway. Overall, these findings provide new insights into M. tb mechanisms to evade host defenses and might contribute to identifying potential therapeutic and vaccine targets for tuberculosis prevention.
Keyphrases
- mycobacterium tuberculosis
- pulmonary tuberculosis
- global health
- signaling pathway
- cell wall
- endothelial cells
- induced apoptosis
- fatty acid
- biofilm formation
- free survival
- stem cells
- public health
- pulmonary hypertension
- epithelial mesenchymal transition
- pi k akt
- genome wide
- emergency department
- bacillus subtilis
- escherichia coli
- cell proliferation
- oxidative stress
- cell cycle arrest
- induced pluripotent stem cells
- hiv aids
- pluripotent stem cells
- human immunodeficiency virus
- genome wide analysis