CMPK2 restricts Mycobacterium tuberculosis replication and regulates macrophage gene expression

Here, we identify the mitochondrial nucleoside monophosphate kinase CMPK2 as a regulator of macrophage responses to Mycobacterium tuberculosis (Mtb). Using a targeted genetic screen of candidate host factors, we found that depletion of CMPK2 enhances intracellular Mtb replication in human macrophages.

This phenotype was confirmed using both shRNA-mediated knockdown and CRISPR-Cas9-mediated knockout approaches. CMPK2 expression increased following macrophage activation and Mtb infection. Transcriptomic profiling revealed that loss of CMPK2 is associated with broad alterations in gene expression, including reduced expression of genes linked to innate immune and inflammatory responses early after infection.