Mavintramycin A is a promising antibiotic for treating <i>Mycobacterium avium</i> complex infectious disease
Kanji Hosoda, Nobuhiro Koyama, Satoru Shigeno, Tomoyasu Nishimura, Naoki Hasegawa, Akihiko Kanamoto, Taichi Ohshiro, Hiroshi Tomoda
Abstract
ABSTRACT Mycobacterium avium complex (MAC) is a serious disease that is mainly caused by infection with the non-tuberculous mycobacteria (NTM), Mycobacterium avium and Mycobacterium intracellulare . Seven new compounds, designated mavintramycins A–G ( 1 – 7 ), were isolated along with structurally related compounds, including amicetin ( 9 ) and plicacetin ( 10 ), from the culture broth of Streptomyces sp. OPMA40551 as anti-MAC compounds that were active against M. avium and M. intracellulare . Among them, mavintramycin A showed the most potent and selective inhibition of M. avium and M. intracellulare . Furthermore, mavintramycin A was active against more than 40 clinically isolated M. avium , including multidrug-resistant strains, and inhibited the growth of M. avium in a persistent infection cell model using THP-1 macrophages. Mavintramycin A also exhibited in vivo efficacy in silkworm and mouse infection assays with NTM. An experiment to elucidate its mechanism of action revealed that mavintramycin A inhibits protein synthesis by binding to 23S ribosomal RNA in NTM. Mavintramycin A, with a different chemical structure from those of clinically used agents, is a promising drug candidate for the treatment of MAC infectious disease.