The autophagy-resistant Mycobacterium tuberculosis Beijing strain upregulates KatG to evade starvation-induced autophagic restriction. Issue 1 (17th January 2022)

• Record Type: Journal Article
• Authors: Siregar, Tegar Adriansyah Putra; Prombutara, Pinidphon; Kanjanasirirat, Phongthon; Kunkaew, Nawapol; Tubsuwan, Alisa; Boonmee, Atsadang; Palaga, Tanapat; Khumpanied, Tanawadee; Borwornpinyo, Suparerk; Chaiprasert, Angkana; Utaisincharoen, Pongsak; Ponpuak, Marisa
• Is Part Of: Pathogens and disease. Volume 80:Issue 1(2022)
• Publication Date: 2022-01-17
• Subjects: Mycobacterium tuberculosis -- tutophagy -- tuberculosis -- ROS -- KatG -- CRISPR; Medical microbiology -- Periodicals; Pathogenic microorganisms -- Periodicals; Communicable diseases -- Microbiology -- Periodicals; Communicable diseases -- Pathogenesis -- Periodicals; Host-parasite relationships -- Periodicals; Systems biology -- Periodicals; 616.904105
• DOI: 10.1093/femspd/ftac004
• Languages: English
• ISSNs: 2049-632X

Abstract

Abstract: Mycobacterium tuberculosis utilizes several mechanisms to block phagosome–lysosome fusion to evade host cell restriction. However, induction of host cell autophagy by starvation was shown to overcome this block, resulting in enhanced lysosomal delivery to mycobacterial phagosomes and the killing of the M. tuberculosis reference strain H37Rv. Nevertheless, our previous studies found that strains belonging to the M. tuberculosis Beijing genotype can resist starvation-induced autophagic elimination, though the mycobacterial factors involved remain unclear. In this study, we showed that KatG expression is upregulated in the autophagy-resistant M. tuberculosis Beijing strain (BJN) during autophagy induction by the starvation of host macrophages, while such increase was not observed in the H37Rv. KatG depletion using the CRISPR-dCas9 interference system in the BJN resulted in increased lysosomal delivery to its phagosome and decreased its survival upon autophagy induction by starvation. As KatG functions by catabolizing ROS, we determined the source of ROS contributing to the starvation-induced autophagic elimination of mycobacteria. Using siRNA-mediated knockdown, we found that Superoxide dismutase 2, which generates mitochondrial ROS but not NADPH oxidase 2, is important for the starvation-induced lysosomal delivery to mycobacterial phagosomes. Taken together, these findings showed that KatG is vital for the BJN to evade starvation-induced autophagic restriction. Abstract : A new role of KatG in autophagy evasion by M. tuberculosis .