Abstract
Almost 3% of the proteins of Mycobacterium tuberculosis (M. tuberculosis), the main causative agent of human tuberculosis, are lipoproteins. These lipoproteins are characteristic of the mycobacterial cell envelope and participate in many mechanisms involved in the pathogenesis of M. tuberculosis. In this review, the authors provide an updated analysis of M. tuberculosis lipoproteins and categorize them according to their demonstrated or predicted functions, including transport of compounds to and from the cytoplasm, biosynthesis of the mycobacterial cell envelope, defense and resistance mechanisms, enzymatic activities and signaling pathways. In addition, this updated analysis revealed that at least 40% of M. tuberculosis lipoproteins are glycosylated.
Tweetable abstract
Almost 3% of proteins of Mycobacterium tuberculosis, the main causative agent of human tuberculosis, are lipoproteins. This review provides an updated analysis of M. tuberculosis lipoproteins and categorizes them according to their demonstrated or predicted functions.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1. . Lipoprotein biogenesis in Gram-positive bacteria: knowing when to hold ‘em, knowing when to fold 'em. Trends Microbiol. 17(1), 13–21 (2009).
- 2. . Role of mycobacteria-induced monocyte/macrophage apoptosis in the pathogenesis of human tuberculosis. Int. J. Tuberc. Lung Dis. 9(4), 375–383 (2005).
- 3. . Lipoproteins of Mycobacterium tuberculosis: an abundant and functionally diverse class of cell envelope components. FEMS Microbiol. Rev. 28(5), 645–659 (2004). • A seminal revision regarding lipoproteins in M. tuberculosis.
- 4. . Lipoproteins of bacterial pathogens. Infect. Immun. 79(2), 548–561 (2011).
- 5. . Lipoprotein synthesis in mycobacteria. Microbiology 153(3), 652–658 (2007). •• Described the synthesis, localization and functions of lipoproteins in mycobacteria.
- 6. . Mycobacterium tuberculosis lipoproteins in virulence and immunity–fighting with a double-edged sword. FEBS Lett. 590(21), 3800–3819 (2016).
- 7. Identification of apolipoprotein N-acyltransferase (Lnt) in mycobacteria. J. Biol. Chem. 284(40), 27146–27156 (2009).
- 8. . Lipoproteins of slow-growing mycobacteria carry three fatty acids and are N-acylated by apolipoprotein N-acyltransferase BCG-2070c. BMC Microbiol. 13(1), 1–15 (2013).
- 9. . Identification of functional Tat signal sequences in Mycobacterium tuberculosis proteins. J. Bacteriol. 190(19), 6428–6438 (2008). •• Identified signal sequences capable of exporting mycobacterial proteins in a Tat-dependent manner.
- 10. . Export-mediated assembly of mycobacterial glycoproteins parallels eukaryotic pathways. Science 309(5736), 166–168 (2005). •• Demonstrated that specific translocation processes are required for protein O-mannosylation in M. tuberculosis.
- 11. . Mycobacteria and their sweet proteins: an overview of protein glycosylation and lipoglycosylation in M. tuberculosis. Tuberculosis 115, 1–13 (2019). • Described protein glycosylation in M. tuberculosis and acylation of glycosylated proteins.
- 12. . Analysis of post-translational modification of mycobacterial proteins using a cassette expression system. FEBS Lett. 473(3), 358–362 (2000).
- 13. Mycobacterium tuberculosis glycoproteomics based on ConA-lectin affinity capture of mannosylated proteins. J. Proteome Res. 8(2), 721–733 (2009). •• Identified glycoproteins in M. tuberculosis for the first time.
- 14. . O-linked glycosylation sites profiling in Mycobacterium tuberculosis culture filtrate proteins. J. Proteomics 97, 296–306 (2014). • The first glycoproteomics study identifying glycosylation sites on mycobacterial culture filtrate proteins on a global scale.
- 15. . Integrative proteomic and glycoproteomic profiling of Mycobacterium tuberculosis culture filtrate. PLoS One 15(3), 1–23 (2020). •• Amassive identification of glycoproteins in M. tuberculosis by shotgun analysis of culture filtrate proteins.
- 16. Ample glycosylation in membrane and cell envelope proteins may explain the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex. Sci. Rep. 9(1), 1–15 (2019).
- 17. Bacterial protein-O-mannosylating enzyme is crucial for virulence of Mycobacterium tuberculosis. Proc. Natl Acad. Sci. USA 110(16), 6560–6565 (2013).
- 18. . Identification of four novel DC-SIGN ligands on Mycobacterium bovis BCG. Protein Cell 1(9), 859–870 (2010).
- 19. Protein O-mannosylation deficiency increases LprG-associated lipoarabinomannan release by Mycobacterium tuberculosis and enhances the TLR2-associated inflammatory response. Sci. Rep. 7(1), 1–14 (2017).
- 20. Conserved mycobacterial lipoglycoproteins activate TLR2 but also require glycosylation for MHC class II-restricted T cell activation. J. Immunol. 180(9), 5833–5842 (2008).
- 21. . Lipoproteins in Gram-positive bacteria: abundance, function, fitness. Front. Microbiol. 11, 1–15 (2020).
- 22. An oligopeptide transporter of Mycobacterium tuberculosis regulates cytokine release and apoptosis of infected macrophages. PLOS ONE 5(8), 1–10 (2010).
- 23. . Trehalose-recycling ABC transporter LpqY-SugA-SugB-SugC is essential for virulence of Mycobacterium tuberculosis. Proc. Natl Acad. Sci. USA 107(50), 21761–21766 (2010).
- 24. Biophysical analysis of the Mycobacteria tuberculosis peptide binding protein DppA reveals a stringent peptide binding pocket. Tuberculosis (Edinb.) 132, 1–26 (2022).
- 25. . Crystal structure of the Mycobacterium tuberculosis phosphate binding protein PstS3. Proteins 82(9), 2268–2274 (2014).
- 26. An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity. Proc. Natl Acad. Sci. USA 111(18), 6750–6755 (2014).
- 27. Mycobacterium tuberculosis with disruption in genes encoding the phosphate binding proteins PstS1 and PstS2 is deficient in phosphate uptake and demonstrates reduced in vivo virulence. Infect. Immun. 73(3), 1898–1902 (2005).
- 28. . Role of an orphan substrate-binding protein MhuP in transient heme transfer in Mycobacterium tuberculosis. Int. J. Biol. Macromol. 211, 342–356 (2022).
- 29. Structural basis of trehalose recognition by the mycobacterial LpqY-SugABC transporter. J. Biol. Chem. 296, 1–12 (2021).
- 30. . Mycobacterial MCE proteins as transporters that control lipid homeostasis of the cell wall. Tuberculosis (Edinb.) 132, 1–6 (2022).
- 31. Structural basis of glycerophosphodiester recognition by the Mycobacterium tuberculosis substrate-binding protein UgpB. ACS Chem. Biol. 14(9), 1879–1887 (2019).
- 32. . Sulfolipid accumulation in Mycobacterium tuberculosis disrupted in the mce2 operon. J. Microbiol. 49(3), 441–447 (2011).
- 33. Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis. BMC Microbiol. 13(1), 200–209 (2013).
- 34. Role of the Mce1 transporter in the lipid homeostasis of Mycobacterium tuberculosis. Tuberculosis (Edinb.) 94(2), 170–177 (2014).
- 35. The hydrolase LpqI primes mycobacterial peptidoglycan recycling. Nat. Commun. 10(1), 1–11 (2019).
- 36. Identification of a novel protein with a role in lipoarabinomannan biosynthesis in mycobacteria. J. Biol. Chem. 281(14), 9011–9017 (2006).
- 37. . Molecular basis of phosphatidyl-myo-inositol mannoside biosynthesis and regulation in mycobacteria. J. Biol. Chem. 285(44), 33577–33583 (2010).
- 38. LprG-mediated surface expression of lipoarabinomannan is essential for virulence of Mycobacterium tuberculosis. PLoS Pathog. 10(9), e1004376 (2014).
- 39. . Characterization of a novel cell wall-anchored protein with carboxylesterase activity required for virulence in Mycobacterium tuberculosis. J. Biol. Chem. 282(25), 18348–18356 (2007).
- 40. Peptidoglycan synthesis in Mycobacterium tuberculosis is organized into networks with varying drug susceptibility. Proc. Natl Acad. Sci. USA 112(42), 13087–13092 (2015).
- 41. . Genetic characterization of mycobacterial L,D-transpeptidases. Microbiology 160(Pt 8), 1795–1806 (2014).
- 42. . Disruption of msl3 abolishes the synthesis of mycolipanoic and mycolipenic acids required for polyacyltrehalose synthesis in Mycobacterium tuberculosis H37Rv and causes cell aggregation. Mol. Microbiol. 45(5), 1451–1459 (2002).
- 43. LppX is a lipoprotein required for the translocation of phthiocerol dimycocerosates to the surface of Mycobacterium tuberculosis. EMBO J. 25(7), 1436–1444 (2006).
- 44. . Resuscitation-promoting factors as lytic enzymes for bacterial growth and signaling. FEMS Immunol. Med. Microbiol. 58(1), 39–50 (2010).
- 45. Mycobacterial metabolic syndrome: LprG and Rv1410 regulate triacylglyceride levels, growth rate and virulence in Mycobacterium tuberculosis. PLOS Pathog. 12(1), 1- 26 (2016).
- 46. Characterization of P55, a multidrug efflux pump in Mycobacterium bovis and Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 45(3), 800–804 (2001).
- 47. Role of P27–P55 operon from Mycobacterium tuberculosis in the resistance to toxic compounds. BMC Infect. Dis. 11, 195 1 -9 (2011).
- 48. Increased drug permeability of a stiffened mycobacterial outer membrane in cells lacking MFS transporter Rv1410 and lipoprotein LprG. Mol. Microbiol. 111(5), 1263–1282 (2019).
- 49. Structural and functional evidence that lipoprotein LpqN supports cell envelope biogenesis in Mycobacterium tuberculosis. J. Biol. Chem. 294(43), 15711–15723 (2019).
- 50. . Insight into isoprenoid biosynthesis by functional analysis of isoprenyl diphosphate synthases from Mycobacterium vanbaalenii and Mycobacterium tuberculosis. ChemBioChem 21(20), 2931–2938 (2020).
- 51. . A lipoprotein modulates activity of the MtrAB two-component system to provide intrinsic multidrug resistance, cytokinetic control and cell wall homeostasis in Mycobacterium. Mol. Microbiol. 76(2), 348–364 (2010).
- 52. . Rv0132c of Mycobacterium tuberculosis encodes a coenzyme F420-dependent hydroxymycolic acid dehydrogenase. PLoS One 8(12), 1–9 (2013).
- 53. . Crystal structure and functional implications of LprF from Mycobacterium tuberculosis and M. bovis. Acta Crystallogr. D Biol. Crystallogr. 70(Pt 10), 2619–2630 (2014).
- 54. . Association of the Rv0679c protein with lipids and carbohydrates in Mycobacterium tuberculosis/Mycobacterium bovis BCG. Arch. Microbiol. 187(4), 297–311 (2007).
- 55. A screen for protein-protein interactions in live mycobacteria reveals a functional link between the virulence-associated lipid transporter LprG and the mycolyltransferase antigen 85A. ACS Infect. Dis. 3(5), 336–348 (2017).
- 56. . Crystal structure and activity studies of the Mycobacterium tuberculosis β-lactamase reveal its critical role in resistance to β-lactam antibiotics. Antimicrob. Agents Chemother. 50(8), 2762–2771 (2006).
- 57. . Penicillin binding proteins and β-lactamases of Mycobacterium tuberculosis: reexamination of the historical paradigm. mSphere 7(1), 1–10 (2022).
- 58. Lipoprotein LprI of Mycobacterium tuberculosis acts as a lysozyme inhibitor. J. Biol. Chem. 291(6), 2938–2953 (2016).
- 59. . Corynebacterium glutamicum ggtB encodes a functional γ-glutamyl transpeptidase with γ-glutamyl dipeptide synthetic and hydrolytic activity. J. Biotechnol. 232, 99–109 (2016).
- 60. Rv2617c and P36 are virulence factors of pathogenic mycobacteria involved in resistance to oxidative stress. Virulence 10(1), 1026–1033 (2019).
- 61. . The lpqS knockout mutant of Mycobacterium tuberculosis is attenuated in macrophages. Microbiol. Res. 168(7), 407–414 (2013).
- 62. . Identification and subcellular localization of a novel Cu, Zn superoxide dismutase of Mycobacterium tuberculosis. FEBS Lett. 439(1–2), 192–196 (1998).
- 63. Unique features of the sodC-encoded superoxide dismutase from Mycobacterium tuberculosis, a fully functional copper-containing enzyme lacking zinc in the active site. J. Biol. Chem. 279(32), 33447–33455 (2004).
- 64. . Functional analyses of mycobacterial lipoprotein diacylglyceryl transferase and comparative secretome analysis of a mycobacterial lgt mutant. J. Bacteriol. 194(15), 3938–3949 (2012).
- 65. Lipoprotein processing is required for virulence of Mycobacterium tuberculosis. Mol. Microbiol. 52(6), 1543–1552 (2004).
- 66. Characterization of a secretory hydrolase from Mycobacterium tuberculosis sheds critical insight into host lipid utilization by M. tuberculosis. J. Biol. Chem. 292(27), 11326–11335 (2017).
- 67. . LpqM, a mycobacterial lipoprotein-metalloproteinase, is required for conjugal DNA transfer in Mycobacterium smegmatis. J. Bacteriol. 191(8), 2721–2727 (2009).
- 68. The Psp system of Mycobacterium tuberculosis integrates envelope stress-sensing and envelope-preserving functions. Mol. Microbiol. 97(3), 408–422 (2015).
- 69. . Interaction of the sensor module of Mycobacterium tuberculosis H37Rv KdpD with members of the Lpr family. Mol. Microbiol. 47(4), 1075–1089 (2003).
- 70. An aspartate-specific solute-binding protein regulates protein kinase G activity to control glutamate metabolism in mycobacteria. MBio 9(4), 1–13 (2018).
- 71. . Crystal structures of YBHB and YBCL from Escherichia coli, two bacterial homologues to a Raf kinase inhibitor protein. J. Mol. Biol. 310(3), 617–634 (2001).
- 72. . Deciphering the polycistronic nature of Mycobacterium tuberculosis lipoproteins of unknown functions. BioRxiv
doi:2023.07.16.549196 1–10 (2023). - 73. . Biochemical and structural characterization of CYP124: a methyl-branched lipid omega-hydroxylase from Mycobacterium tuberculosis. Proc. Natl Acad. Sci. USA 106(49), 20687–20692 (2009).
- 74. . Biochemical characterization of the Mycobacterium tuberculosis phosphoribosyl-1-pyrophosphate synthetase. Glycobiology 21(4), 410–425 (2011).
- 75. . Genetic requirements for mycobacterial survival during infection. Proc. Natl Acad. Sci. USA 100(22), 12989–12994 (2003).
- 76. . MPB70 and MPB83–major antigens of Mycobacterium bovis. Scand. J. Immunol. 69(6), 492–499 (2009).
- 77. . Modulation of host immune responses by overexpression of immunodominant antigens of Mycobacterium tuberculosis in Bacille Calmette-Guérin. Scand. J. Immunol. 58(4), 449–461 (2003).
- 78. Comprehensive essentiality analysis of the Mycobacterium tuberculosis genome via saturating transposon mutagenesis. MBio 8(1), 1–17 (2017).
- 79. Genomewide assessment of Mycobacterium tuberculosis conditionally essential metabolic pathways. mSystems 4(4), 1–13 (2019).
- 80. . Genome-wide requirements for Mycobacterium tuberculosis adaptation and survival in macrophages. Proc. Natl Acad. Sci. USA 102(23), 8327–8332 (2005).
- 81. . Identification of a virulence gene cluster of Mycobacterium tuberculosis by signature-tagged transposon mutagenesis. Mol. Microbiol. 34(2), 257–267 (1999).
- 82. Mycobacterium bovis Δmce2 double deletion mutant protects cattle against challenge with virulent M. bovis. Tuberculosis (Edinb.) 93(3), 363–372 (2013).
- 83. Effect of deletion or overexpression of the 19-kilodalton lipoprotein Rv3763 on the innate response to Mycobacterium tuberculosis. Infect. Immun. 73(10), 6831–6837 (2005).
- 84. . Mycobacterium tuberculosis LprE suppresses TLR2-dependent cathelicidin and autophagy expression to enhance bacterial survival in macrophages. J. Immunol. 203(10), 2665–2678 (2019).
- 85. . Mycobacterium tuberculosis LprG (Rv1411c): a novel TLR-2 ligand that inhibits human macrophage class II MHC antigen processing. J. Immunol. 173(4), 2660–2668 (2004).
- 86. Knockout mutation of p27–p55 operon severely reduces replication of Mycobacterium bovis in a macrophagic cell line and survival in a mouse model of infection. Virulence 2(3), 233–237 (2011).
- 87. . Shotgun proteomic profiling of dormant, ‘non-culturable’ Mycobacterium tuberculosis. PLOS ONE 17(8), 1–26 (2022).
- 88. Proteomic profiling of Mycobacterium tuberculosis identifies nutrient-starvation-responsive toxin-antitoxin systems. Mol. Cell. Proteomics 12(5), 1180–1191 (2013).
- 89. . Phosphate starvation enhances phagocytosis of Mycobacterium bovis/BCG by macrophages. BMC Immunol. 21(1), 1–8 (2020).
- 90. Transcriptional profiling of Mycobacterium tuberculosis exposed to in vitro lysosomal stress. Infect. Immun. 84(9), 2505–2523 (2016).
- 91. Mycobacteria release active membrane vesicles that modulate immune responses in a TLR2-dependent manner in mice. J. Clin. Invest. 121(4), 1471–1483 (2011).
- 92. The 19-kDa antigen of Mycobacterium tuberculosis is a major adhesin that binds the mannose receptor of THP-1 monocytic cells and promotes phagocytosis of mycobacteria. Microb. Pathog. 39(3), 97–107 (2005).
- 93. . Mycobacterium tuberculosis LprA is a lipoprotein agonist of TLR2 that regulates innate immunity and APC function. J. Immunol. 177(1), 422–429 (2006).
- 94. Cloning of the gene encoding a 22-kilodalton cell surface antigen of Mycobacterium bovis BCG and analysis of its potential for DNA vaccination against tuberculosis. Infect. Immun. 68(3), 1040–1047 (2000).
- 95. Toll-like receptor 2-dependent inhibition of macrophage class II MHC expression and antigen processing by 19-kDa lipoprotein of Mycobacterium tuberculosis. J. Immunol. 167(2), 910–918 (2001).
- 96. . PstS-1, the 38-kDa Mycobacterium tuberculosis glycoprotein, is an adhesin, which binds the macrophage mannose receptor and promotes phagocytosis. Scand. J. Immunol. 81(1), 46–55 (2015).
- 97. Recombinant lipoprotein Rv1016c derived from Mycobacterium tuberculosis is a TLR-2 ligand that induces macrophages apoptosis and inhibits MHC II antigen processing. Front. Cell. Infect. Microbiol. 6(NOV), 1–13 (2016).
- 98. Mycobacterial lipoprotein activates autophagy via TLR2/1/CD14 and a functional vitamin D receptor signalling. Cell. Microbiol. 12(11), 1648–1665 (2010).
- 99. LppM impact on the colonization of macrophages by Mycobacterium tuberculosis. Cell. Microbiol. 19(1), 1–11 (2017).
- 100. Mycobacterium bovis requires P27 (LprG) to arrest phagosome maturation and replicate within bovine macrophages. Infect. Immun. 85(3), 1–11 (2017).
- 101. . The 19 kDa Mycobacterium tuberculosis lipoprotein (LpqH) induces macrophage apoptosis through extrinsic and intrinsic pathways: a role for the mitochondrial apoptosis-inducing factor. Clin. Dev. Immunol. 2012, 1–11 (2012).
- 102. . Mycobacterium tuberculosis 38-kDa lipoprotein is apoptogenic for human monocyte-derived macrophages. Scand. J. Immunol. 69(1), 20–28 (2009).
- 103. . Rv3033, as an emerging anti-apoptosis factor, facilitates mycobacteria survival via inhibiting macrophage intrinsic apoptosis. Front. Immunol. 9(SEP), 1–11 (2018).
- 104. Mycobacterium tuberculosis Rv2224c modulates innate immune responses. Proc. Natl Acad. Sci. USA 105(1), 264–269 (2008).
- 105. Mycobacterium tuberculosis PstS1 amplifies IFN-γ and induces IL-17/IL-22 responses by unrelated memory CD4+ T cells via dendritic cell activation. Eur. J. Immunol. 43(9), 2386–2397 (2013).
- 106. Mycobacterial lipoprotein Z triggers efficient innate and adaptive immunity for protection against Mycobacterium tuberculosis infection. Front. Immunol. 9(JAN), 1–13 (2019).
- 107. Mycobacterium tuberculosis Rv0309 dampens the inflammatory response and enhances mycobacterial survival. Front. Immunol. 13(FEB), 1–19 (2022).
- 108. . Aggravated infection in mice co-administered with Mycobacterium tuberculosis and the 27-kDa lipoprotein. Microbes Infect. 8(7), 1750–1757 (2006).
- 109. Mycobacterium tuberculosis glycolipoprotein LprG inhibits inflammation through NF-κB signaling of ERK1/2 and JNK in LPS-induced murine macrophage cells. J. Cell. Biochem. 123(4), 772–781 (2022).
- 110. Immunodominant PstS1 antigen of Mycobacterium tuberculosis is a potent biological response modifier for the treatment of bladder cancer. BMC Cancer 4, 1–14 (2004).
- 111. Chemical genetic interaction profiling reveals determinants of intrinsic antibiotic resistance in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 61(12), 1–15 (2017).
- 112. . PPE surface proteins are required for heme utilization by Mycobacterium tuberculosis. MBio 8(1),1–14 (2017).
- 113. Mce3R, a TetR-type transcriptional repressor, controls the expression of a regulon involved in lipid metabolism in Mycobacterium tuberculosis. Microbiology 155(7), 2245–2255 (2009).
- 114. . Glycine betaine uptake by the proXVWZ ABC transporter contributes to the ability of Mycobacterium tuberculosis to initiate growth in human macrophages. J. Bacteriol. 190(11), 3955–3961 (2008).
- 115. . The putative compatible solute-binding protein ProX from Mycobacterium tuberculosis H37Rv: biochemical characterization and crystallographic data. Acta Crystallogr. Sect. F Struct. Biol. Commun. 74(4), 231–235 (2018).
- 116. Three different putative phosphate transport receptors are encoded by the Mycobacterium tuberculosis genome and are present at the surface of Mycobacterium bovis BCG. J. Bacteriol. 179(9), 2900–2906 (1997).
- 117. Mycobacterium tuberculosis LppM displays an original structure and domain composition linked to a dual localization. Structure 24(10), 1788–1794 ( 2016).
- 118. . Novel protein acetyltransferase, Rv2170, modulates carbon and energy metabolism in Mycobacterium tuberculosis. Sci. Rep. 7(1), 1–11 (2017).
- 119. . Definition of novel cell envelope associated proteins in Triton X-114 extracts of Mycobacterium tuberculosis H37Rv. BMC Microbiol. 10, 1–11 (2010).
- 120. . Cell-wall synthesis and ribosome maturation are co-regulated by an RNA switch in Mycobacterium tuberculosis. Nucleic Acids Res. 46(11), 5837–5849 (2018).
- 121. M. tuberculosis Rv2252 encodes a diacylglycerol kinase involved in the biosynthesis of phosphatidylinositol mannosides (PIMs). Mol. Microbiol. 60(5), 1152–1163 (2006).
- 122. Proteomics of culture filtrate of prevalent Mycobacterium tuberculosis strains: 2D-PAGE Map and MALDI-TOF/MS analysis. SLAS Discov. 22(9), 1142–1149 (2017).
- 123. . ADP-ribosylation systems in bacteria and viruses. Comput. Struct. Biotechnol. J. 19, 2366–2383 (2021).
- 124. . The macro domain protein family: structure, functions, and their potential therapeutic implications. Mutat. Res. 727(3), 86–103 (2011).
- 125. . Insights into the biogenesis, function, and regulation of ADP-ribosylation. Nat. Chem. Biol. 14(3), 236–243 (2018).
- 126. . The lipolytic activity of LipJ, a stress-induced enzyme, is regulated by its C-terminal adenylate cyclase domain. Future Microbiol. 16(7), 2020–0223 (2021).
- 127. . A multicopper oxidase is required for copper resistance in Mycobacterium tuberculosis. J. Bacteriol. 195(16), 3724–3733 (2013).
- 128. . Overexpression, purification, and characterization of VanX, a D-, D-dipeptidase which is essential for vancomycin resistance in Enterococcus faecium BM4147. Biochemistry 34(8), 2455–63 (1995).
- 129. The Rv2633c protein of Mycobacterium tuberculosis is a non-heme di-iron catalase with a possible role in defenses against oxidative stress. J. Biol. Chem. 293(5), 1590 (2018).
- 130. . Loss of a class A penicillin-binding protein alters β-lactam susceptibilities in Mycobacterium tuberculosis. ACS Infect. Dis. 2(2), 104–110 (2016).
- 131. An extracellular disulfide bond forming protein (DsbF) from Mycobacterium tuberculosis: structural, biochemical, and gene expression analysis. J. Mol. Biol. 396(5), 1211–1226 (2010).
- 132. . Identification of the polyketide synthase involved in the biosynthesis of the surface-exposed lipooligosaccharides in mycobacteria. J. Bacteriol. 191(8), 2613–2621 (2009).
- 133. Pks5-recombination-mediated surface remodelling in Mycobacterium tuberculosis emergence. Nat. Microbiol. 1(2), 1–11 (2016).
- 134. The nucleotide messenger (p)ppGpp is an anti-inducer of the purine synthesis transcription regulator PurR in Bacillus. Nucleic Acids Res. 50(2), 847–866 (2022).
- 135. . Radiation-sensitive gene A (RadA) targets DisA, DNA integrity scanning protein A, to negatively affect cyclic Di-AMP synthesis activity in Mycobacterium smegmatis. J. Biol. Chem. 288(31), 22426– 22436 (2013).
- 136. . Mycobacterium tuberculosis Rv3586 (DacA) is a diadenylate cyclase that converts ATP or ADP into c-di-AMP. PLoS One 7(4), 1–10 (2012).
- 137. . Unusual diheme conformation of the heme-degrading protein from Mycobacterium tuberculosis. J. Mol. Biol. 395(3), 595–608 (2010).
- 138. A lysine acetyltransferase contributes to the metabolic adaptation to hypoxia in Mycobacterium tuberculosis. Cell Chem. Biol. 25(12), 1495–1505.e3 (2018).
- 139. LpqT improves mycobacteria survival in macrophages by inhibiting TLR2-mediated inflammatory cytokine expression and cell apoptosis. Tuberculosis 111, 57–66 (2018).
- 140. The knockout of the lprG-Rv1410 operon produces strong attenuation of Mycobacterium tuberculosis. Microbes Infect. 6(2), 182–187 (2004).
- 141. . LspA inactivation in Mycobacterium tuberculosis results in attenuation without affecting phagosome maturation arrest. Microbiology 154(10), 2991–3001 (2008).
- 142. . Unraveling the structure of the mycobacterial envelope. Microbiol. Spectr. 7(4), 1–11 (2019).