Lipid metabolism and type VII secretion systems dominate the genome scale virulence profile of Mycobacterium tuberculosis in human dendritic cells

BMC Genomics

Volumn 16, Issue 1, 2015, Pages

  Mendum, Tom A ^a   Wu, Huihai ^a   Kierzek, Andrzej M ^a   Stewart, Graham R ^a  

^a UNIVERSITY OF SURREY   (United Kingdom)

Author keywords

cholesterol; dendritic cells; ESX systems; Mycobacterium tuberculosis; nitrate reductase; phenolic glycolipids; phthiocerol dimycolates; PPE genes; sulfolipid; transposon library

Indexed keywords

CYSTEINE; DNA; EARLY SECRETORY ANTIGENIC TARGET 6; LIPID; METHIONINE; NITRATE REDUCTASE; VIRULENCE FACTOR; CHOLESTEROL; REACTIVE NITROGEN SPECIES; TRANSPOSON; TYPE VII SECRETION SYSTEM;

ARTICLE; BACTERIAL GENE; BACTERIAL GENOME; BACTERIAL SECRETION SYSTEM; BACTERIAL VIRULENCE; BACTERIUM CULTURE; CATABOLISM; CELL SURVIVAL; CONTROLLED STUDY; DENDRITIC CELL; DNA PURIFICATION; FLOW CYTOMETRY; GENE AMPLIFICATION; GENE IDENTIFICATION; GENE INTERACTION; GENE LOCUS; GENE MUTATION; HUMAN; HUMAN CELL; LIPID METABOLISM; MUTANT; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; NUTRIENT; SEQUENCE ANALYSIS; TRANSPOSON; TUBERCULOSIS; TYPE VII SECRETION SYSTEM; CELL WALL; CYTOLOGY; GENETICS; GENOMICS; MACROPHAGE; METABOLISM; MICROBIOLOGY; MUTATION; OXIDATIVE STRESS; PATHOGENICITY; PHAGOSOME; VIRULENCE;

BACTERIA (MICROORGANISMS); MYCOBACTERIUM TUBERCULOSIS;

CELL WALL; CHOLESTEROL; DENDRITIC CELLS; DNA TRANSPOSABLE ELEMENTS; GENOME, BACTERIAL; GENOMICS; HUMANS; LIPID METABOLISM; MACROPHAGES; MUTATION; MYCOBACTERIUM TUBERCULOSIS; OXIDATIVE STRESS; PHAGOSOMES; REACTIVE NITROGEN SPECIES; TYPE VII SECRETION SYSTEMS; VIRULENCE;

EID: 84929154082     PISSN: None     EISSN: 14712164     Source Type: Journal    
DOI: 10.1186/s12864-015-1569-2     Document Type: Article

References (134)

1. Dye C, Williams BG. The Population Dynamics and Control of Tuberculosis. Science. 2010;328:856-61.
2. Eum SY, Kong JH, Hong MS, Lee YJ, Kim JH, Hwang SH, et al. Neutrophils Are the Predominant Infected Phagocytic Cells in the Airways of Patients With Active Pulmonary TB. CHEST Journal. 2010;137:122-8.
3. Wolf AJ, Linas B, Trevejo-Nuñez GJ, Kincaid E, Tamura T, Takatsu K, et al. Mycobacterium tuberculosis Infects Dendritic Cells with High Frequency and Impairs Their Function In Vivo. The Journal of Immunology. 2007;179:2509-19.
4. Garcia-Romo GS, Pedroza-Gonzalez A, Lambrecht BN, Aquilar-Leon D, Estrada-Garcia I, Hernandez-Pando R, et al. Mycobacterium tuberculosis manipulates pulmonary APCs subverting early immune responses. Immunobiology. 2013;218:393-401.
5. Segal AW, Geisow M, Garcia R, Harper A, Miller R. The respiratory burst of phagocytic cells is associated with a rise in vacuolar pH. Nature. 1981;290:406-9.
6. Persson YA, Blomgran-Julinder R, Rahman S, Zheng L, Stendahl O. Mycobacterium tuberculosis-induced apoptotic neutrophils trigger a pro-inflammatory response in macrophages through release of heat shock protein 72, acting in synergy with the bacteria. Microbes and Infection. 2008;10:233-40.
7. Hedlund S, Persson A, Vujic A, Che KF, Stendahl O, Larsson M. Dendritic cell activation by sensing Mycobacterium tuberculosisG€"induced apoptotic neutrophils via DC-SIGN. Human Immunology. 2010;71:535-40.
8. Sturgill-Koszycki S, Schlesinger PH, Chakraborty P, Haddix PL, Collins HL, Fok AK, et al. Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton-ATPase. Science. 1994;263:678-81.
9. Russell DG, Dant J, Sturgill-Koszycki S. Mycobacterium avium- and Mycobacterium tuberculosis-containing vacuoles are dynamic, fusion-competent vesicles that are accessible to glycosphingolipids from the host cell plasmalemma. J Immunol. 1996;156:4764-73.
10. Russell DG. Mycobacterium tuberculosis: here today, and here tomorrow. Nat Rev Mol Cell Biol. 2001;2:569-77.
11. Munoz-Elias EJ, McKinney JD. Mycobacterium tuberculosis isocitrate lyases 1 and 2 are jointly required for in vivo growth and virulence. Nat Med. 2005;11:638-44.
12. Pandey AK, Sassetti CM. Mycobacterial persistence requires the utilization of host cholesterol. Proc Natl Acad Sci U S A. 2008;105:4376-80.
13. Beste DJ, Noh K, Niedenfuhr S, Mendum TA, Hawkins ND, Ward JL, et al. 13C-flux spectral analysis of host-pathogen metabolism reveals a mixed diet for intracellular Mycobacterium tuberculosis. Chem Biol. 2013;20:1012-21.
14. Doz E, Rose S, Nigou J, Gilleron M, Puzo G, Erard F, et al. Acylation determines the toll-like receptor (TLR)-dependent positive versus TLR2-, mannose receptor-, and SIGNR1-independent negative regulation of pro-inflammatory cytokines by mycobacterial lipomannan. J Biol Chem. 2007;282:26014-25.
15. Harding CV, Boom WH. Regulation of antigen presentation by Mycobacterium tuberculosis: a role for Toll-like receptors. Nat Rev Microbiol. 2010;8:296-307.
16. Butler RE, Brodin P, Jang J, Jang MS, Robertson BD, Gicquel B, et al. The balance of apoptotic and necrotic cell death in Mycobacterium tuberculosis infected macrophages is not dependent on bacterial virulence. PLoS One. 2012;7, e47573.
17. Keane J, Remold HG, Kornfeld H. Virulent Mycobacterium tuberculosis strains evade apoptosis of infected alveolar macrophages. J Immunol. 2000;164:2016-20.
18. Forrellad MA, Klepp LI, Gioffre A, Sabioy Garcia J, Morbidoni HR, de la Paz Santangelo M, et al. Virulence factors of the Mycobacterium tuberculosis complex. Virulence. 2013;4:3-66.
19. Rosas-Magallanes V, Stadthagen-Gomez G, Rauzier J, Barreiro LB, Tailleux L, Boudou F, et al. Signature-tagged transposon mutagenesis identifies novel Mycobacterium tuberculosis genes involved in the parasitism of human macrophages. Infect Immun. 2007;75:504-7.
20. Camacho LR, Ensergueix D, Perez E, Gicquel B, Guilhot C. Identification of a virulence gene cluster of Mycobacterium tuberculosis by signature-tagged transposon mutagenesis. Molecular Microbiology. 1999;34:257-67.
21. Rengarajan J, Bloom BR, Rubin EJ. Genome-wide requirements for Mycobacterium tuberculosis adaptation and survival in macrophages. Proc Natl Acad Sci USA. 2005;102:8327-32.
22. Stewart GR, Patel J, Robertson BD, Rae A, Young DB. Mycobacterial mutants with defective control of phagosomal acidification. PLoS Pathog. 2005;1:269-78.
23. Mihret A, Mamo G, Tafesse M, Hailu A, Parida S. Dendritic Cells Activate and Mature after Infection with Mycobacterium tuberculosis. BMC Research Notes. 2011;4:247.
24. Henderson RA, Watkins SC, Flynn JL. Activation of human dendritic cells following infection with Mycobacterium tuberculosis. The Journal of Immunology. 1997;159:635-43.
25. Geijtenbeek T, Van Vliet SJ, Koppel EA, Sanchez-Hernandez M, Vandenbroucke-Grauls CM, Appelmelk B, et al. Mycobacteria target DC-SIGN to suppress dendritic cell function. J Exp Med. 2003;197:7.
26. Hava DL, van der Wel N, Cohen N, Dascher CC, Houben D, León L, et al. Evasion of peptide, but not lipid antigen presentation, through pathogen-induced dendritic cell maturation. Proceedings of the National Academy of Sciences. 2008;105:11281-6.
27. Demangel C, Bertolino P, Britton WJ. Autocrine IL-10 impairs dendritic cell (DC)-derived immune responses to mycobacterial infection by suppressing DC trafficking to draining lymph nodes and local IL-12 production. European Journal of Immunology. 2002;32:994-1002.
28. Buettner M, Meinken C, Bastian M, Bhat R, St-Ýssel E, Faller G, et al. Inverse Correlation of Maturity and Antibacterial Activity in Human Dendritic Cells. The Journal of Immunology. 2005;174:4203-9.
29. Tailleux L, Neyrolles O, Honoré-Bouakline S, Perret E, Sanchez FO, Abastado JP, et al. Constrained Intracellular Survival of Mycobacterium tuberculosis in Human Dendritic Cells. The Journal of Immunology. 2003;170:1939-48.
30. Bodnar KA, Serbina NV, Flynn JL. Fate of Mycobacterium tuberculosis within murine dendritic cells. Infect Immun. 2001;69:800-9.
31. Romagnoli A, Etna MP, Giacomini E, Pardini M, Remoli ME, Corazzari M, et al. ESX-1 dependent impairment of autophagic flux by Mycobacterium tuberculosis in human dendritic cells. Autophagy. 2012;8:1357-70.
32. Tailleux L, Waddell SJ, Pelizzola M, Mortellaro A, Withers M, Tanne A, et al. Probing host pathogen cross-talk by transcriptional profiling of both Mycobacterium tuberculosis and infected human dendritic cells and macrophages. PLoS ONE. 2008;3, e1403.
33. van der Wel N, Hava D, Houben D, Fluitsma D, van Zon M, Pierson J, et al. M. tuberculosis and M. leprae Translocate from the Phagolysosome to the Cytosol in Myeloid Cells. Cell. 2007;129:1287-98.
34. Pethe K, Swenson DL, Alonso S, Anderson J, Wang C, Russell DG. Isolation of Mycobacterium tuberculosis mutants defective in the arrest of phagosome maturation. Proc Natl Acad Sci USA. 2004;101:13642-7.
35. Walburger A, Koul A, Ferrari G, Nguyen L, Prescianotto-Baschong C, Huygen K, et al. Protein Kinase G from Pathogenic Mycobacteria Promotes Survival Within Macrophages. Science. 2004;304:1800-4.
36. Caminero JA, Pena MJ, Campos-Herrero MI, Rodriguez JC, Garcia I, Cabrera P, et al. Epidemiological evidence of the spread of a Mycobacterium tuberculosis strain of the Beijing genotype on Gran Canaria Island. Am J Respir Crit Care Med. 2001;164:1165-70.
37. Sassetti CM, Rubin EJ. Genetic requirements for mycobacterial survival during infection. Proc Natl Acad Sci U S A. 2003;100:12989-94.
38. Fortsch D, Rollinghoff M, Stenger S. IL-10 converts human dendritic cells into macrophage-like cells with increased antibacterial activity against virulent Mycobacterium tuberculosis. J Immunol. 2000;165:978-87.
39. Rivero-Lezcano OM, Gonzalez-Cortes C, Reyes-Ruvalcaba D, Diez-Tascon C. CCL20 is overexpressed in Mycobacterium tuberculosis-infected monocytes and inhibits the production of reactive oxygen species (ROS). Clin Exp Immunol. 2010;162:289-97.
40. Olakanmi O, Kesavalu B, Abdalla MY, Britigan BE. Iron acquisition by Mycobacterium tuberculosis residing within myeloid dendritic cells. Microbial Pathogenesis. 2013;65:21-8.
41. Ryan R, O'Sullivan M, Keane J. Mycobacterium tuberculosis infection induces non-apoptotic cell death of human dendritic cells. BMC Microbiology. 2011;11:237.
42. Abdalla H, Srinivasan L, Shah S, Mayer-Barber KD, Sher A, Sutterwala FS, et al. Mycobacterium tuberculosis Infection of Dendritic Cells Leads to Partially Caspase-1/11-Independent IL-1β and IL-18 Secretion but Not to Pyroptosis. PLoS ONE. 2012;7, e40722.
43. Zhang YJ, Ioerger TR, Huttenhower C, Long JE, Sassetti CM, Sacchettini JC, et al. Global assessment of genomic regions required for growth in Mycobacterium tuberculosis. PLoS Pathog. 2012;8, e1002946.
44. Cox JS, Chen B, McNeil M, Jacobs Jr WR. Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice. Nature. 1999;402:79-83.
45. Simeone R, Huet G, Constant P, Malaga W, Lemassu A, Laval F, et al. Functional characterisation of three o-methyltransferases involved in the biosynthesis of phenolglycolipids in Mycobacterium tuberculosis. PLoS One. 2013;8, e58954.
46. Kendall SL, Burgess P, Balhana R, Withers M, Ten Bokum A, Lott JS, et al. Cholesterol utilization in mycobacteria is controlled by two TetR-type transcriptional regulators: kstR and kstR2. Microbiology. 2010;156:1362-71.
47. Mohn WW, van der Geize R, Stewart GR, Okamoto S, Liu J, Dijkhuizen L, et al. The actinobacterial mce4 locus encodes a steroid transporter. J Biol Chem. 2008;283:35368-74.
48. Griffin J-E, Pandey A-K, Gilmore S-A, Mizrahi V, McKinney J-D, Bertozzi C-R, et al. Cholesterol Catabolism by Mycobacterium tuberculosis Requires Transcriptional and Metabolic Adaptations. Chemistry & Biology. 2012;19:218-27.
49. Houben EN, Korotkov KV, Bitter W. Take five - Type VII secretion systems of Mycobacteria. Biochim Biophys Acta. 1843;2014:1707-16.
50. Diamant I, Eldar YC, Rokhlenko O, Ruppin E, Shlomi T. A network-based method for predicting gene-nutrient interactions and its application to yeast amino-acid metabolism. Mol Biosyst. 2009;5:1732-9.
51. Beste DJ, Hooper T, Stewart G, Bonde B, Avignone-Rossa C, Bushell ME, et al. GSMN-TB: a web-based genome-scale network model of Mycobacterium tuberculosis metabolism. Genome Biol. 2007;8:R89.
52. Reed MB, Domenech P, Manca C, Su H, Barczak AK, Kreiswirth BN, et al. A glycolipid of hypervirulent tuberculosis strains that inhibits the innate immune response. Nature. 2004;431:84-7.
53. Huet G, Constant P, Malaga W, Laneelle MA, Kremer K, van Soolingen D, et al. A lipid profile typifies the Beijing strains of Mycobacterium tuberculosis: identification of a mutation responsible for a modification of the structures of phthiocerol dimycocerosates and phenolic glycolipids. J Biol Chem. 2009;284:27101-13.
54. Dhar N, McKinney JD. Mycobacterium tuberculosis persistence mutants identified by screening in isoniazid-treated mice. Proc Natl Acad Sci U S A. 2010;107:12275-80.
55. Sirakova TD, Dubey VS, Cynamon MH, Kolattukudy PE. Attenuation of Mycobacterium tuberculosis by disruption of a mas-like gene or a chalcone synthase-like gene, which causes deficiency in dimycocerosyl phthiocerol synthesis. J Bacteriol. 2003;185:2999-3008.
56. Passemar C, Arbués A, Malaga W, Mercier I, Moreau F, Lepourry L, et al. Multiple deletions in the polyketide synthase gene repertoire of Mycobacterium tuberculosis reveal functional overlap of cell envelope lipids in host-pathogen interactions. Cellular Microbiology. 2013;16:195-213.
57. Perez E, Constant P, Lemassu A, Laval F, Daffe M, Guilhot C. Characterization of three glycosyltransferases involved in the biosynthesis of the phenolic glycolipid antigens from the Mycobacterium tuberculosis complex. J Biol Chem. 2004;279:42574-83.
58. Indrigo J, Hunter Jr RL, Actor JK. Cord factor trehalose 6,6'-dimycolate (TDM) mediates trafficking events during mycobacterial infection of murine macrophages. Microbiology. 2003;149:2049-59.
59. Armitige LY, Jagannath C, Wanger AR, Norris SJ. Disruption of the genes encoding antigen 85A and antigen 85B of Mycobacterium tuberculosis H37Rv: effect on growth in culture and in macrophages. Infect Immun. 2000;68:767-78.
60. Belisle JT, Vissa VD, Sievert T, Takayama K, Brennan PJ, Besra GS. Role of the Major Antigen of Mycobacterium tuberculosis in Cell Wall Biogenesis. Science. 1997;276:1420-2.
61. Katti MK, Dai G, Armitige LY, Rivera Marrero C, Daniel S, Singh CR, et al. The Delta fbpA mutant derived from Mycobacterium tuberculosis H37Rv has an enhanced susceptibility to intracellular antimicrobial oxidative mechanisms, undergoes limited phagosome maturation and activates macrophages and dendritic cells. Cell Microbiol. 2008;10:1286-303.
62. Puech V, Guilhot C, Perez E, Tropis M, Armitige LY, Gicquel B, et al. Evidence for a partial redundancy of the fibronectin-binding proteins for the transfer of mycoloyl residues onto the cell wall arabinogalactan termini of Mycobacterium tuberculosis. Mol Microbiol. 2002;44:1109-22.
63. Hatzios SK, Schelle MW, Holsclaw CM, Behrens CR, Botyanszki Z, Lin FL, et al. PapA3 is an acyltransferase required for polyacyltrehalose biosynthesis in Mycobacterium tuberculosis. J Biol Chem. 2009;284:12745-51.
64. Rodriguez JE, Ramirez AS, Salas LP, Helguera-Repetto C, Gonzalez-y-Merchand J, Soto CY, et al. Transcription of genes involved in sulfolipid and polyacyltrehalose biosynthesis of Mycobacterium tuberculosis in experimental latent tuberculosis infection. PLoS One. 2013;8, e58378.
65. Barkan D, Rao V, Sukenick GD, Glickman MS. Redundant function of cmaA2 and mmaA2 in Mycobacterium tuberculosis cis cyclopropanation of oxygenated mycolates. J Bacteriol. 2010;192:3661-8.
66. Yuan Y, Zhu Y, Crane DD, Barry Iii CE. The effect of oxygenated mycolic acid composition on cell wall function and macrophage growth in Mycobacterium tuberculosis. Molecular Microbiology. 1998;29:1449-58.
67. Dao DN, Sweeney K, Hsu T, Gurcha SS, Nascimento IP, Roshevsky D, et al. Mycolic acid modification by the mmaA4 gene of M. tuberculosis modulates IL-12 production. PLoS Pathog. 2008;4:e1000081.
68. Boissier F, Bardou F, Guillet V, Uttenweiler-Joseph S, Daffe M, Quemard A, et al. Further insight into S-adenosylmethionine-dependent methyltransferases: structural characterization of Hma, an enzyme essential for the biosynthesis of oxygenated mycolic acids in Mycobacterium tuberculosis. J Biol Chem. 2006;281:4434-45.
69. McAdam RA, Quan S, Smith DA, Bardarov S, Betts JC, Cook FC, et al. Characterization of a Mycobacterium tuberculosis H37Rv transposon library reveals insertions in 351 ORFs and mutants with altered virulence. Microbiology. 2002;148:2975-86.
70. Dubnau E, Chan J, Raynaud C, Mohan VP, Lanéelle M-A, Yu K, et al. Oxygenated mycolic acids are necessary for virulence of Mycobacterium tuberculosis in mice. Molecular Microbiology. 2000;36:630-7.
71. Middlebrook G, Coleman CM, Schaefer WB. Sulfolipid from virulent tubercle bacilli. Proceedings of the National Academy of Sciences. 1959;45:1801-4.
72. Zhang L, Goren MB, Holzer TJ, Andersen BR. Effect of Mycobacterium tuberculosis-derived sulfolipid I on human phagocytic cells. Infection and Immunity. 1988;56:2876-83.
73. Pabst MJ, Gross JM, Brozna JP, Goren MB. Inhibition of macrophage priming by sulfatide from Mycobacterium tuberculosis. J Immunol. 1988;140:634-40.
74. Gilmore SA, Schelle MW, Holsclaw CM, Leigh CD, Jain M, Cox JS, et al. Sulfolipid-1 biosynthesis restricts Mycobacterium tuberculosis growth in human macrophages. ACS Chem Biol. 2012;7:863-70.
75. Kumar P, Schelle MW, Jain M, Lin FL, Petzold CJ, Leavell MD, et al. PapA1 and PapA2 are acyltransferases essential for the biosynthesis of the Mycobacterium tuberculosis virulence factor sulfolipid-1. Proc Natl Acad Sci U S A. 2007;104:11221-6.
76. Converse SE, Mougous JD, Leavell MD, Leary JA, Bertozzi CR, Cox JS. MmpL8 is required for sulfolipid-1 biosynthesis and Mycobacterium tuberculosis virulence. Proc Natl Acad Sci U S A. 2003;100:6121-6.
77. Lynett J, Stokes RW. Selection of transposon mutants of Mycobacterium tuberculosis with increased macrophage infectivity identifies fadD23 to be involved in sulfolipid production and association with macrophages. Microbiology. 2007;153:3133-40.
78. McAdam RA, Weisbrod TR, Martin J, Scuderi JD, Brown AM, Cirillo JD, et al. In vivo growth characteristics of leucine and methionine auxotrophic mutants of Mycobacterium bovis BCG generated by transposon mutagenesis. Infect Immun. 1995;63:1004-12.
79. DeJesus MA, Zhang YJ, Sassetti CM, Rubin EJ, Sacchettini JC, Ioerger TR. Bayesian analysis of gene essentiality based on sequencing of transposon insertion libraries. Bioinformatics. 2013;29:695-703.
80. Fukuda T, Matsumura T, Ato M, Hamasaki M, Nishiuchi Y, Murakami Y, et al. Critical roles for lipomannan and lipoarabinomannan in cell wall integrity of mycobacteria and pathogenesis of tuberculosis. MBio. 2013;4:e00472-00412.
81. Mishra AK, Driessen NN, Appelmelk BJ, Besra GS. Lipoarabinomannan and related glycoconjugates: structure, biogenesis and role in Mycobacterium tuberculosis physiology and host-pathogen interaction. FEMS Microbiol Rev. 2011;35:1126-57.
82. Welin A, Winberg ME, Abdalla H, Sarndahl E, Rasmusson B, Stendahl O, et al. Incorporation of Mycobacterium tuberculosis lipoarabinomannan into macrophage membrane rafts is a prerequisite for the phagosomal maturation block. Infect Immun. 2008;76:2882-7.
83. Afonso-Barroso A, Clark SO, Williams A, Rosa GT, Nobrega C, Silva-Gomes S, et al.: Lipoarabinomannan mannose caps do not affect mycobacterial virulence or the induction of protective immunity in experimental animal models of infection and have minimal impact on in vitro inflammatory responses. Cell Microbiol 2013;15:660-74.
84. Pitarque S, Herrmann JL, Duteyrat JL, Jackson M, Stewart GR, Lecointe F, et al. Deciphering the molecular bases of Mycobacterium tuberculosis binding to the lectin DC-SIGN reveals an underestimated complexity. Biochem J. 2005;392:615-24.
85. Ouellet H, Johnston JB, de Montellano PR. Cholesterol catabolism as a therapeutic target in Mycobacterium tuberculosis. Trends Microbiol. 2011;19:530-9.
86. Lee EJ, Pontes MH, Groisman EA. A bacterial virulence protein promotes pathogenicity by inhibiting the bacterium's own F1F0 ATP synthase. Cell. 2013;154:146-56.
87. Jain M, Petzold CJ, Schelle MW, Leavell MD, Mougous JD, Bertozzi CR, et al. Lipidomics reveals control of Mycobacterium tuberculosis virulence lipids via metabolic coupling. Proc Natl Acad Sci U S A. 2007;104:5133-8.
88. Colangeli R, Haq A, Arcus VL, Summers E, Magliozzo RS, McBride A, et al. The multifunctional histone-like protein Lsr2 protects mycobacteria against reactive oxygen intermediates. Proc Natl Acad Sci U S A. 2009;106:4414-8.
89. Klink M, Brzezinska M, Szulc I, Brzostek A, Kielbik M, Sulowska Z, et al. Cholesterol oxidase is indispensable in the pathogenesis of Mycobacterium tuberculosis. PLoS One. 2013;8, e73333.
90. Nguyen DH, Taub DD. Inhibition of chemokine receptor function by membrane cholesterol oxidation. Exp Cell Res. 2003;291:36-45.
91. Bednarska K, Kielbik M, Sulowska Z, Dziadek J: Cholesterol Oxidase Binds TLR2 and Modulates Functional Responses of Human Macrophages. Mediators Inflamm. 2014:498395.
92. Kendall SL, Withers M, Soffair CN, Moreland NJ, Gurcha S, Sidders B, et al. A highly conserved transcriptional repressor controls a large regulon involved in lipid degradation in Mycobacterium smegmatis and Mycobacterium tuberculosis. Mol Microbiol. 2007;65:684-99.
93. Slayden RA, Jackson M, Zucker J, Ramirez MV, Dawson CC, Crew R, et al. Updating and curating metabolic pathways of TB. Tuberculosis. 2013;93:47-59.
94. Chang JC, Harik NS, Liao RP, Sherman DR. Identification of Mycobacterial genes that alter growth and pathology in macrophages and in mice. J InfectDis. 2007;196:788-95.
95. Thomas ST, VanderVen BC, Sherman DR, Russell DG, Sampson NS. Pathway profiling in Mycobacterium tuberculosis: elucidation of cholesterol-derived catabolite and enzymes that catalyze its metabolism. J Biol Chem. 2011;286:43668-78.
96. Casabon I, Zhu SH, Otani H, Liu J, Mohn WW, Eltis LD. Regulation of the KstR2 regulon of Mycobacterium tuberculosis by a cholesterol catabolite. Mol Microbiol. 2013;89:1201-12.
97. MacGurn JA, Cox JS. A Genetic Screen for Mycobacterium tuberculosis Mutants Defective for Phagosome Maturation Arrest Identifies Components of the ESX-1 Secretion System. Infection and Immunity. 2007;75:2668-78.
98. Brodin P, Poquet Y, Levillain F, Peguillet I, Larrouy-Maumus G, Gilleron M, et al. High Content Phenotypic Cell-Based Visual Screen Identifies Mycobacterium tuberculosis Acyltrehalose-Containing Glycolipids Involved in Phagosome Remodeling. PLoS Pathog. 2010;6, e1001100.
99. Vergne I, Chua J, Lee HH, Lucas M, Belisle J, Deretic V. Mechanism of phagolysosome biogenesis block by viable Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2005;102:4033-8.
100. Thi EP, Hong CJ, Sanghera G, Reiner NE. Identification of the Mycobacterium tuberculosis protein PE-PGRS62 as a novel effector that functions to block phagosome maturation and inhibit iNOS expression. Cell Microbiol. 2013;15:795-808.
101. Iantomasi R, Sali M, Cascioferro A, Palucci I, Zumbo A, Soldini S, et al. PE_PGRS30 is required for the full virulence of Mycobacterium tuberculosis. Cell Microbiol. 2012;14:356-67.
102. Kim KH, An DR, Song J, Yoon JY, Kim HS, Yoon HJ, et al. Mycobacterium tuberculosis Eis protein initiates suppression of host immune responses by acetylation of DUSP16/MKP-7. Proc Natl Acad Sci U S A. 2012;109:7729-34.
103. Fratti RA, Chua J, Vergne I, Deretic V. Mycobacterium tuberculosis glycosylated phosphatidylinositol causes phagosome maturation arrest. Proceedings of the National Academy of Sciences. 2003;100:5437-42.
104. Siegrist MS, Unnikrishnan M, McConnell MJ, Borowsky M, Cheng TY, Siddiqi N, et al. Mycobacterial Esx-3 is required for mycobactin-mediated iron acquisition. Proc Natl Acad Sci U S A. 2009;106:18792-7.
105. Di Luca M, Bottai D, Batoni G, Orgeur M, Aulicino A, Counoupas C, et al. The ESX-5 associated eccB-EccC locus is essential for Mycobacterium tuberculosis viability. PLoS One. 2012;7, e52059.
106. Stoop EJ, Bitter W, van der Sar AM. Tubercle bacilli rely on a type VII army for pathogenicity. Trends Microbiol. 2012;20:477-84.
107. Bottai D, Majlessi L, Simeone R, Frigui W, Laurent C, Lenormand P, et al. ESAT-6 Secretion-Independent Impact of ESX-1 Genes espF and espG1 on Virulence of Mycobacterium tuberculosis. Journal of Infectious Diseases. 2011;203:1155-64.
108. Chen JM, Zhang M, Rybniker J, Basterra L, Dhar N, Tischler AD, et al. Phenotypic profiling of Mycobacterium tuberculosis EspA point mutants reveals that blockage of ESAT-6 and CFP-10 secretion in vitro does not always correlate with attenuation of virulence. J Bacteriol. 2013;195:5421-30.
109. Joshi SA, Ball DA, Sun MG, Carlsson F, Watkins BY, Aggarwal N, et al. EccA1, a component of the Mycobacterium marinum ESX-1 protein virulence factor secretion pathway, regulates mycolic acid lipid synthesis. Chem Biol. 2012;19:372-80.
110. Bottai D, Di Luca M, Majlessi L, Frigui W, Simeone R, Sayes F, et al. Disruption of the ESX-5 system of Mycobacterium tuberculosis causes loss of PPE protein secretion, reduction of cell wall integrity and strong attenuation. Mol Microbiol. 2012;83:1195-209.
111. Abdallah AM, Verboom T, Weerdenburg EM, van Pittius NC G, Mahasha PW, Jimenez C, et al. PPE and PE_PGRS proteins of Mycobacterium marinum are transported via the type VII secretion system ESX-5. Mol Microbiol. 2009;73:329-40.
112. Daleke MH, Ummels R, Bawono P, Heringa J, Vandenbroucke-Grauls CM, Luirink J, et al. General secretion signal for the mycobacterial type VII secretion pathway. Proc Natl Acad Sci U S A. 2012;109:11342-7.
113. Akhter Y, Ehebauer MT, Mukhopadhyay S, Hasnain SE. The PE/PPE multigene family codes for virulence factors and is a possible source of mycobacterial antigenic variation: perhaps more? Biochimie. 2012;94:110-6.
114. Werling D, Hope JC, Howard CJ, Jungi TW. Differential production of cytokines, reactive oxygen and nitrogen by bovine macrophages and dendritic cells stimulated with Toll-like receptor agonists. Immunology. 2004;111:41-52.
115. Ehrt S, Schnappinger D. Mycobacterial survival strategies in the phagosome: defence against host stresses. Cell Microbiol. 2009;11:1170-8.
116. Senaratne RH, De Silva AD, Williams SJ, Mougous JD, Reader JR, Zhang T, et al. 5-Adenosinephosphosulphate reductase (CysH) protects Mycobacterium tuberculosis against free radicals during chronic infection phase in mice. Molecular Microbiology. 2006;59:1744-53.
117. Voskuil MI, Schnappinger D, Rutherford R, Liu Y, Schoolnik GK. Regulation of the Mycobacterium tuberculosis PE/PPE genes. Tuberculosis. 2004;84:256-62.
118. Patil AG, Sang PB, Govindan A, Varshney U. Mycobacterium tuberculosis MutT1 (Rv2985) and ADPRase (Rv1700) proteins constitute a two-stage mechanism of 8-oxo-dGTP and 8-oxo-GTP detoxification and adenosine to cytidine mutation avoidance. J Biol Chem. 2013;288:11252-62.
119. Hillas PJ, del Alba FS, Oyarzabal J, Wilks A, Ortiz De Montellano PR. The AhpC and AhpD antioxidant defense system of Mycobacterium tuberculosis. J Biol Chem. 2000;275:18801-9.
120. Newton GL, Av-Gay Y, Fahey RC. N-Acetyl-1-D-myo-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside deacetylase (MshB) is a key enzyme in mycothiol biosynthesis. J Bacteriol. 2000;182:6958-63.
121. Buchmeier NA, Newton GL, Koledin T, Fahey RC. Association of mycothiol with protection of Mycobacterium tuberculosis from toxic oxidants and antibiotics. Mol Microbiol. 2003;47:1723-32.
122. Cunningham-Bussel A, Zhang T, Nathan CF: Nitrite produced by Mycobacterium tuberculosis in human macrophages in physiologic oxygen impacts bacterial ATP consumption and gene expression. Proc Natl Acad Sci. 2013;110:E4256-65.
123. Darwin KH, Ehrt S, Gutierrez-Ramos JC, Weich N, Nathan CF. The proteasome of Mycobacterium tuberculosis is required for resistance to nitric oxide. Science. 2003;302:1963-6.
124. Houghton J, Townsend C, Williams AR, Rodgers A, Rand L, Walker KB, et al. Important role for Mycobacterium tuberculosis UvrD1 in pathogenesis and persistence apart from its function in nucleotide excision repair. J Bacteriol. 2012;194:2916-23.
125. Jung JY, Madan-Lala R, Georgieva M, Rengarajan J, Sohaskey CD, Bange FC, et al. The intracellular environment of human macrophages that produce nitric oxide promotes growth of mycobacteria. Infect Immun. 2013;81:3198-209.
126. Herbst S, Schaible UE, Schneider BE. Interferon gamma activated macrophages kill mycobacteria by nitric oxide induced apoptosis. PLoS One. 2011;6, e19105.
127. Tan MP, Sequeira P, Lin WW, Phong WY, Cliff P, Ng SH, et al. Nitrate respiration protects hypoxic Mycobacterium tuberculosis against acid- and reactive nitrogen species stresses. PLoS One. 2010;5, e13356.
128. Cunningham-Bussel A, Bange FC, Nathan CF. Nitrite impacts the survival of Mycobacterium tuberculosis in response to isoniazid and hydrogen peroxide. Microbiologyopen. 2013;2:901-11.
129. Bardarov S, Kriakov J, Carriere C, Yu S, Vaamonde C, McAdam RA, et al. Conditionally replicating mycobacteriophages: a system for transposon delivery to Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 1997;94:10961-6.
130. Rubin EJ, Akerley BJ, Novik VN, Lampe DJ, Husson RN, Mekalanos JJ. In vivo transposition of mariner-based elements in enteric bacteria and mycobacteria. Proc Natl Acad Sci U S A. 1999;96:1645-50.
131. Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Meth. 2012;9:357-9.
132. Nadarajah S, Kotz S. A generalized logistic distribution. International Journal of Mathematics and Mathematical Sciences. 2005;2005:3169-74.
133. Loughin TM. A systematic comparison of methods for combining p-values from independent tests. Computational Statistics & Data Analysis. 2004;47:467-85.
134. Gevorgyan A, Bushell ME, Avignone-Rossa C, Kierzek AM. SurreyFBA: a command line tool and graphics user interface for constraint-based modeling of genome-scale metabolic reaction networks. Bioinformatics. 2011;27:433-4.