NapM, a new nucleoid-associated protein, broadly regulates gene expression and affects mycobacterial resistance to anti-tuberculosis drugs

Abstract

Nucleoid-associated proteins (NAPs) play important roles in the global organization of bacterial chromosomes. However, potential NAPs and their functions are barely characterized in mycobacteria. In this study, NapM, an alkaline protein, functions as a new NAP. NapM is conserved in all of the sequenced mycobacterial genomes, and can recognize DNA in a length-dependent but sequence-independent manner. It prefers AT-rich DNA and binds to the major groove. NapM possesses a clear DNA-bridging function, and can protect DNA from DNase I digestion. NapM globally regulates the expression of more than 150 genes and the resistance of Mycobacterium smegmatis to two anti-tuberculosis drugs, namely, rifampicin and ethambutol. An ABC transporter operon was found to be specifically responsible for the napM-dependent ethambutol resistance of M. smegmatis. NapM also presents a similar regulation of anti-tuberculosis drug resistance in M. tuberculosis. These results suggest that NapM is a new member of the mycobacterial NAP family. Our findings expand the range of identified NAPs and improve the understanding on the relationship between NAPs with antibiotic resistance in mycobacteria.