AUTHOR=Lee Duhyung , Kim Dong Hyun , Seo Hyejun , Choi Seaone , Kim Bum-Joon 

TITLE=Phylogenetic distribution of malonate semialdehyde decarboxylase (MSAD) genes among strains within the genus Mycobacterium: evidence of MSAD gene loss in the evolution of pathogenic mycobacteria

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1275616

DOI=10.3389/fmicb.2023.1275616

ISSN=1664-302X

ABSTRACT=<p>Despite the great diversity of malonate semialdehyde decarboxylases (MSADs), one of five subgroups of the tautomerase superfamily (TSF) found throughout the biosphere, their distribution among strains within the genus <italic>Mycobacterium</italic> remains unknown. In this study, we sought to investigate the phylogenetic distribution of MSAD genes of mycobacterial species via genome analysis of 192 different reference <italic>Mycobacterium</italic> species or subspecies retrieved from NCBI databases. We found that in a total of 87 of 192 strains (45.3%), MSAD-1 and MSAD-2 were distributed in an exclusive manner among <italic>Mycobacterium</italic> species except for 12 strains, including <italic>Mycobacterium chelonae</italic> members, with both in their genome. Of note, <italic>Mycobacterium</italic> strains better adapted to the host and of high virulence potential, such as the <italic>Mycobacterium tuberculosis</italic> complex, <italic>Mycobacterium leprae</italic>, <italic>Mycobacterium marinum</italic>, <italic>Mycobacterium ulcerans</italic>, and <italic>Mycobacterium avium</italic> subsp. <italic>paratuberculosis</italic>, had no orthologs of MSAD in their genome, suggesting MSAD loss during species differentiation in pathogenic slow-growing <italic>Mycobacterium</italic>. To investigate the MSAD distribution among strains of <italic>M. avium</italic> subspecies, the genome sequences of a total of 255 reference strains from the four subspecies of <italic>M. avium</italic> (43 of subspecies <italic>avium</italic>, 162 of subspecies <italic>hominissuis</italic>, 49 of subspecies <italic>paratuberculosis</italic>, and 1 of subspecies <italic>silvaticum</italic>) were further analyzed. We found that only 121 of 255 strains (47.4%) had MSADs in their genome, with none of the 49 <italic>M. avium</italic> subsp. <italic>paratuberculosis</italic> strains having MSAD genes. Even in 13 of 121 <italic>M. avium</italic> strains with the MSAD-1 gene in their genome, deletion mutations in the 98th codon causing premature termination of MSAD were found, further highlighting the occurrence of MSAD pseudogenization during species or subspecies differentiation of <italic>M. avium.</italic> In conclusion, our data indicated that there are two distinct types of MSADs, MSAD-1 and MSAD-2, among strains in the <italic>Mycobacterium</italic> genus, but more than half of the strains, including pathogenic mycobacteria, <italic>M. tuberculosis</italic> and <italic>M. leprae</italic>, have no orthologs in their genome, suggesting MSAD loss during host adaptation of pathogenic mycobacteria. In the future, the role of two distinct MSADs, MSAD-1 and MSAD-2, in mycobacterial pathogenesis or evolution should be investigated.</p>