AUTHOR=Jia Liqiu , Sha Shanshan , Yang Shufeng , Taj Ayaz , Ma Yufang 

TITLE=Effect of Protein O-Mannosyltransferase (MSMEG_5447) on M. smegmatis and Its Survival in Macrophages

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.657726

DOI=10.3389/fmicb.2021.657726

ISSN=1664-302X

ABSTRACT=<p>Protein O-mannosyltransferase (PMT) catalyzes an initial step of protein O-mannosylation of <italic>Mycobacterium tuberculosis</italic> (Mtb) and plays a crucial role for Mtb survival in the host. To better understand the role of PMT in the host innate immune response during mycobacterial infection, in this study, we utilized <italic>Mycobacterium smegmatis</italic> pmt (<italic>MSMEG_5447</italic>) gene knockout strain, ΔM5447, to infect THP-1 cells. Our results revealed that the lack of <italic>MSMEG_5447</italic> not only impaired the growth of <italic>M. smegmatis</italic> in 7H9 medium but also reduced the resistance of <italic>M. smegmatis</italic> against lysozyme and acidic stress <italic>in vitro</italic>. Macrophage infection assay showed that ΔM5447 displayed attenuated growth in macrophages at 24 h post-infection. The production of TNF-α and IL-6 and the activation of transcription factor NF-κB were decreased in ΔM5447-infected macrophages, which were further confirmed by transcriptomic analysis. Moreover, ΔM5447 failed to inhibit phagosome–lysosome fusion in macrophages. These findings revealed that PMT played a role in modulating the innate immune responses of the host, which broaden our understanding for functions of protein O-mannosylation in mycobacterium–host interaction.</p>