Transcriptional profiling of M. intracellulare under acidic and oxidative stress conditions
Mycobacterium avium complex (MAC), including Mycobacterium avium and Mycobacterium intracellulare (MI), accounts for a significant portion of nontuberculous mycobacterial lung disease affecting immunocompromised and lung structural disease patients. Adapting pathogens to a host-induced hostile environment is critical to establishing infection and persistence within the host. However, the cellular and molecular mechanisms of stress response for MAC still need to be elucidated. In this study, we analyzed the transcriptional profile of MI under acidic and oxidative stress conditions using RNA-seq. At the transcriptome level, 80 genes were shown [FC] =2.0 and p <0.05 under oxidative stress with 10 mM hydrogen peroxide. In detail, 77 genes were upregulated, while 3 genes were downregulated. Also, 878 genes were shown [FC] =2.0 and p <0.05 under acidic stress with pH 4.5. Among these genes, 339 were upregulated, while 539 were downregulated. Functional analysis revealed the activation of several pathways, including nitrogen and sulfur metabolism, under acidic stress conditions. On the contrary, oxidative stress conditions activated DNA replication and repair pathways. Our data demonstrate the activation of nitrogen and sulfur metabolism in MAC infection, which could be crucial for persistence and survival under stress conditions encountered within the host during infection. In conclusion, this study suggests the importance of stress responses in MAC pathogenesis and identifies potential therapeutic target pathways. Overall design: To elucidate the transcriptional changes of Mycobacterium intracellulare under host-induced stress, we conducted RNA-seq with Mycobacterium intracellulare under acidic and oxidative stress conditions.