Fluorescence-based visual analysis and inhibitor screening of Arylamine N-acetyltransferase 2, a key enzyme for tuberculosis

Tuberculosis is a global epidemic caused by pathogenic Mycobacterium tuberculosis (Mtb), which seriously threatens human life. Arylamine N-acetyltransferase 2 (NAT2) is a vital enzyme in the synthesis of Mtb wall, and closely related to the growth of Mtb. Herein, a fluorescence-based recognition tool (BDPN) has been developed for rapid, sensitive, and selective detection of NAT2 activity in Mtb. As well as a visual high-throughput screening approach for NAT2 inhibitors was established based on BDPN, and four active natural compounds derived from Psoraleae Fructus were discovered that exhibited strong inhibitory effect toward NAT2. Furthermore, Isobavachalcone exhibited the considerable anti-tuberculosis effect through prominently destroying the bacterial cell wall of Mtb and slow down its growth. Moreover, Isobavachalcone could delay the elimination of the anti-tuberculosis drug Isoniazid (INH) mediated by NAT2 and enhance anti-tuberculosis effect of INH. In summary, BDPN was a promising tool for monitoring endogenous NAT2 in Mtb and provided some useful guidance for the rational administration of anti-tuberculosis drug.