Mycobacterium smegmatis MSMEG_6906 modulates IL-1β via NF-κB pathway to benefit intracellular survival.

Tuberculosis (TB), instigated by Mycobacterium tuberculosis (Mtb), exerts a detrimental impact on public health worldwide. Mtb features unique and abundant lipids components and genes involved in lipogenesis, which are believed to provide the pathogen an advantage in the host, but the underlying mechanisms remain inconclusive. In the present study we show that Mycobacterium smegmatis (M. smegmatis) MSMEG_6906, annotated as a hydrolase that probably involved in lipid biosynthesis, functions in affecting bacterial morphology, and plays a role in modulating IL-1β expression in macrophages. The absence of MSMEG_6906 results in significantly attenuated survival of M. smegmatis in macrophages. Mechanistically, MSMEG_6906 suppresses the expression of IL-1β through nuclear factor-κB (NF-κB) signaling pathway, thus benefiting the survival of M. smegmatis in macrophages. Exogenously added IL-1β neutralizing antibody could partially rescue the bacterial load of MSMEG_6906 deficient strain to the level of wild type M. smegmatis in macrophages. Our findings broaden understanding on the interplay between mycobacterium and host immune response, provide an alternative for TB treatment or drug development in the future.