Mycobacterial Esx-3 requires multiple components for iron acquisition

mBio

Volumn 5, Issue 3, 2014, Pages

  Sloan Siegrist, M ^a   Steigedal, Magnus ^a,b,c   Ahmad, Rushdy ^d   Mehra, Alka ^e   Dragset, Marte S ^a,b,c   Schuster, Brian M ^a   Philips, Jennifer A ^e   Carr, Steven A ^d   Rubin, Eric J ^a  

^a HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^b NORWEGIAN UNIVERSITY OF SCIENCE AND TECHNOLOGY   (Norway)

^c TRONDHEIM UNIVERSITY HOSPITAL   (Norway)

^d BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^e NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIAL PROTEIN; IRON; MEMBRANE ENZYME; PROTEIN ESX 3; PROTEIN ESXGMS; PROTEIN ESXHMS; PROTEIN MYCP3; PROTEINASE; UNCLASSIFIED DRUG; MYCOBACTINS; OXAZOLE DERIVATIVE;

ARTICLE; BACTERIAL GENE; BACTERIAL GENETICS; BACTERIAL GROWTH; BACTERIAL SECRETION SYSTEM; CONTROLLED STUDY; ESX 3 GENE; IRON STORAGE; MUTANT; MYCOBACTERIUM SMEGMATIS; MYCP3MS GENE; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN TRANSPORT; TYPE VII SECRETION SYSTEM; GENE LOCUS; GENE ORDER; GENETICS; GROWTH, DEVELOPMENT AND AGING; METABOLISM; MYCOBACTERIUM;

BACTERIAL SECRETION SYSTEMS; GENE ORDER; GENETIC LOCI; IRON; MYCOBACTERIUM; OXAZOLES;

EID: 84903978034     PISSN: 21612129     EISSN: 21507511     Source Type: Journal    
DOI: 10.1128/mBio.01073-14     Document Type: Article

References (65)

1. Lewis KN, Liao R, Guinn KM, Hickey MJ, Smith S, Behr MA, Sherman DR. 2003. Deletion of RD1 from Mycobacterium tuberculosis mimics Bacille Calmette-Gu érin attenuation. J. Infect. Dis. 187: 117-123. http://dx. doi. org/10. 1086/345862.
2. Pym AS, Brodin P, Brosch R, Huerre M, Cole ST. 2002. Loss of RD1 contributed to the attenuation of the live tuberculosis vaccines Mycobacterium bovis BCG and Mycobacterium microti. Mol. Microbiol. 46: 709-717. http://dx. doi. org/10. 1046/j. 1365-2958. 2002. 03237. x.
3. Pym AS, Brodin P, Majlessi L, Brosch R, Demangel C, Williams A, Griffiths KE, Marchal G, Leclerc C, Cole ST. 2003. Recombinant BCG exporting ESAT-6 confers enhanced protection against tuberculosis. Nat. Med. 9: 533-539. http://dx. doi. org/10. 1038/nm859.
4. Coros A, Callahan B, Battaglioli E, Derbyshire KM. 2008. The specialized secretory apparatus ESX-1 is essential for DNA transfer in Mycobacterium smegmatis. Mol. Microbiol. 69: 794-808. http://dx. doi. org/10. 1111/j. 1365-2958. 2008. 06299. x.
5. Flint JL, Kowalski JC, Karnati PK, Derbyshire KM. 2004. The RD1 virulence locus of Mycobacterium tuberculosis regulates DNA transfer in Mycobacterium smegmatis. Proc. Natl. Acad. Sci. U. S. A. 101: 12598-12603. http://dx. doi. org/10. 1073/pnas. 0404892101.
6. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE, III, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG. 1998. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393: 537-544. http://dx. doi. org/10. 1038/31159.
7. Tekaia F, Gordon SV, Garnier T, Brosch R, Barrell BG, Cole ST. 1999. Analysis of the proteome of Mycobacterium tuberculosis in silico. Tuber. Lung Dis. 79: 329-342. http://dx. doi. org/10. 1054/tuld. 1999. 0220.
8. Gey Van Pittius NC, Gamieldien J, Hide W, Brown GD, Siezen RJ, Beyers AD. 2001. The ESAT-6 gene cluster of Mycobacterium tuberculosis and other high G_C Gram-positive bacteria. Genome Biol. 2: RESEARCH0044. http://dx. doi. org/10. 1186/gb-2001-2-10-research0044.
9. Abdallah AM, Savage ND, van Zon M, Wilson L, Vandenbroucke-Grauls CM, van der Wel NN, Ottenhoff TH, Bitter W. 2008. The ESX-5 secretion system of Mycobacterium marinum modulates the macrophage response. J. Immunol. 181: 7166-7175.
10. Abdallah AM, Verboom T, Hannes F, Safi M, Strong M, Eisenberg D, Musters RJ, Vandenbroucke-Grauls CM, Appelmelk BJ, Luirink J, Bitter W. 2006. A specific secretion system mediates PPE41 transport in pathogenic mycobacteria. Mol. Microbiol. 62: 667-679. http://dx. doi. org/10. 1111/j. 1365-2958. 2006. 05409. x.
11. Abdallah AM, Verboom T, Weerdenburg EM, Gey van Pittius NC, Mahasha PW, Jiménez C, Parra M, Cadieux N, Brennan MJ, Appelmelk BJ, Bitter W. 2009. PPE and PE_PGRS proteins of Mycobacterium marinum are transported via the type VII secretion system ESX-5. Mol. Microbiol. 73: 329-340. http://dx. doi. org/10. 1111/j. 1365-2958. 2009. 06783. x.
12. Serafini A, Boldrin F, Palù G, Manganelli R. 2009. Characterization of a Mycobacterium tuberculosis ESX-3 conditional mutant: essentiality and rescue by iron and zinc. J. Bacteriol. 191: 6340-6344. http://dx. doi. org/10. 1128/JB. 00756-09.
13. Siegrist MS, Unnikrishnan M, McConnell MJ, Borowsky M, Cheng TY, Siddiqi N, Fortune SM, Moody DB, Rubin EJ. 2009. Mycobacterial Esx-3 is required for mycobactin-mediated iron acquisition. Proc. Natl. Acad. Sci. U. S. A. 106: 18792-18797. http://dx. doi. org/10. 1073/pnas. 0900589106.
14. Sweeney KA, Dao DN, Goldberg MF, Hsu T, Venkataswamy MM, Henao-Tamayo M, Ordway D, Sellers RS, Jain P, Chen B, Chen M, Kim J, Lukose R, Chan J, Orme IM, Porcelli SA, Jacobs WR, Jr. 2011. A recombinant Mycobacterium smegmatis induces potent bactericidal immunity against Mycobacterium tuberculosis. Nat. Med. 17: 1261-1268. http://dx. doi. org/10. 1038/nm. 2420.
15. Ilghari D, Lightbody KL, Veverka V, Waters LC, Muskett FW, Renshaw PS, Carr MD. 2011. Solution structure of the Mycobacterium tuberculosis EsxG-EsxH complex: functional implications and comparisons with other M. tuberculosis Esx family complexes. J. Biol. Chem. 286: 29993-30002. http://dx. doi. org/10. 1074/jbc. M111. 248732.
16. Abdallah AM, Bestebroer J, Savage ND, de Punder K, van Zon M, Wilson L, Korbee CJ, van der Sar AM, Ottenhoff TH, van der Wel NN, Bitter W, Peters PJ. 2011. Mycobacterial secretion systems ESX-1 and ESX-5 play distinct roles in host cell death and inflammasome activation. J. Immunol. 187: 4744-4753. http://dx. doi. org/10. 4049/jimmunol. 1101457.
17. Daleke MH, Cascioferro A, de Punder K, Ummels R, Abdallah AM, van der Wel N, Peters PJ, Luirink J, Manganelli R, Bitter W. 2011. Conserved Pro-Glu (PE) and Pro-Pro-Glu (PPE) protein domains target LipY lipases of pathogenic mycobacteria to the cell surface via the ESX-5 pathway. J. Biol. Chem. 286: 19024-19034. http://dx. doi. org/10. 1074/jbc. M110. 204966.
18. Mehra A, Zahra A, Thompson V, Sirisaengtaksin N, Wells A, Porto M, Koster S, Penberthy K, Kubota Y, Dricot A, Rogan D, Vidal M, Hill DE, Bean AJ, Philips JA. 2013. Mycobacterium tuberculosis type VII secreted effector EsxH targets host ESCRT to impair trafficking. PLoS Pathog. 9: e1003734. http://dx. doi. org/10. 1371/journal. ppat. 1003734.
19. Serafini A, Pisu D, Palu G, Rodriguez GM, Manganelli R. 2013. The ESX-3 secretion system is necessary for iron and zinc homeostasis in Mycobacterium tuberculosis. PLoS One 8: e78351. http://dx. doi. org/10. 1371/journal. pone. 0078351.
20. Sassetti CM, Boyd DH, Rubin EJ. 2003. Genes required for mycobacterial growth defined by high density mutagenesis. Mol. Microbiol. 48: 77-84. http://dx. doi. org/10. 1046/j. 1365-2958. 2003. 03425. x.
21. Rodriguez GM, Voskuil MI, Gold B, Schoolnik GK, Smith I. 2002. ideR, an essential gene in Mycobacterium tuberculosis: role of IdeR in irondependent gene expression, iron metabolism, and oxidative stress response. Infect. Immun. 70: 3371-3381. http://dx. doi. org/10. 1128/IAI. 70. 7. 3371-3381. 2002.
22. Maciag A, Dainese E, Rodriguez GM, Milano A, Provvedi R, Pasca MR, Smith I, Palù G, Riccardi G, Manganelli R. 2007. Global analysis of the Mycobacterium tuberculosis Zur (FurB) regulon. J. Bacteriol. 189: 730-740. http://dx. doi. org/10. 1128/JB. 01190-06.
23. Ratledge C, Dover LG. 2000. Iron metabolism in Pathogenic Bacteria. Annu. Rev. Microbiol. 54: 881-941. http://dx. doi. org/10. 1146/annurev. micro. 54. 1. 881.
24. Ratledge C, Ewing M. 1996. The occurrence of carboxymycobactin, the siderophore of pathogenic mycobacteria, as a second extracellular siderophore in Mycobacterium smegmatis. Microbiology 142: 2207-2212. http://dx. doi. org/10. 1099/13500872-142-8-2207.
25. Rodriguez GM. 2006. Control of iron metabolism in Mycobacterium tuberculosis. Trends Microbiol. 14: 320-327. http://dx. doi. org/10. 1016/j. tim. 2006. 05. 006.
26. Jones CM, Niederweis M. 2010. Role of porins in iron uptake by Mycobacterium smegmatis. J. Bacteriol. 192: 6411-6417. http://dx. doi. org/10. 1128/JB. 00986-10.
27. Tullius MV, Harmston CA, Owens CP, Chim N, Morse RP, McMath LM, Iniguez A, Kimmey JM, Sawaya MR, Whitelegge JP, Horwitz MA, Goulding CW. 2011. Discovery and characterization of a unique mycobacterial heme acquisition system. Proc. Natl. Acad. Sci. U. S. A. 108: 5051-5056. http://dx. doi. org/10. 1073/pnas. 1009516108.
28. Jones CM, Niederweis M. 2011. Mycobacterium tuberculosis can utilize heme as an iron source. J. Bacteriol. 193: 1767-1770. http://dx. doi. org/10. 1128/JB. 01312-10.
29. Bitter W, Houben EN, Bottai D, Brodin P, Brown EJ, Cox JS, Derbyshire K, Fortune SM, Gao LY, Liu J, Gey van Pittius NC, Pym AS, Rubin EJ, Sherman DR, Cole ST, Brosch R. 2009. Systematic genetic nomenclature for type VII secretion systems. PLoS Pathog. 5: e1000507. http://dx. doi. org/10. 1371/journal. ppat. 1000507.
30. Abdallah AM, Gey van Pittius NC, Champion PA, Cox J, Luirink J, Vandenbroucke-Grauls CM, Appelmelk BJ, Bitter W. 2007. Type VII secretion-mycobacteria show the way. Nat. Rev. Microbiol. 5:-883-891. http://dx. doi. org/10. 1038/nrmicro1773.
31. Champion PA, Cox JS. 2007. Protein secretion systems in Mycobacteria. Cell. Microbiol. 9: 1376-1384. http://dx. doi. org/10. 1111/j. 1462-5822. 2007. 00943. x.
32. Simeone R, Bottai D, Brosch R. 2009. ESX/type VII secretion systems and their role in host-pathogen interaction. Curr. Opin. Microbiol. 12: 4-10. http://dx. doi. org/10. 1016/j. mib. 2008. 11. 003.
33. MacGurn JA, Raghavan S, Stanley SA, Cox JS. 2005. A non-RD1 gene cluster is required for Snm secretion in Mycobacterium tuberculosis. Mol. Microbiol. 57: 1653-1663. http://dx. doi. org/10. 1111/j. 1365-2958. 2005. 04800. x.
34. Fortune SM, Jaeger A, Sarracino DA, Chase MR, Sassetti CM, Sherman DR, Bloom BR, Rubin EJ. 2005. Mutually dependent secretion of proteins required for mycobacterial virulence. Proc. Natl. Acad. Sci. U. S. A. 102: 10676-10681. http://dx. doi. org/10. 1073/pnas. 0504922102.
35. Brodin P, Majlessi L, Marsollier L, de Jonge MI, Bottai D, Demangel C, Hinds J, Neyrolles O, Butcher PD, Leclerc C, Cole ST, Brosch R. 2006. Dissection of ESAT-6 system 1 of Mycobacterium tuberculosis and impact on immunogenicity and virulence. Infect. Immun. 74: 88-98. http://dx. doi. org/10. 1128/IAI. 74. 1. 88-98. 2006.
36. Converse SE, Cox JS. 2005. A protein secretion pathway critical for Mycobacterium tuberculosis virulence is conserved and functional in Mycobacterium smegmatis. J. Bacteriol. 187: 1238-1245. http://dx. doi. org/10. 1128/JB. 187. 4. 1238-1245. 2005.
37. Gao LY, Guo S, McLaughlin B, Morisaki H, Engel JN, Brown EJ. 2004. A mycobacterial virulence gene cluster extending RD1 is required for cytolysis, bacterial spreading and ESAT-6 secretion. Mol. Microbiol. 53: 1677-1693. http://dx. doi. org/10. 1111/j. 1365-2958. 2004. 04261. x.
38. Guinn KM, Hickey MJ, Mathur SK, Zakel KL, Grotzke JE, Lewinsohn DM, Smith S, Sherman DR. 2004. Individual RD1-region genes are required for export of ESAT-6/CFP-10 and for virulence of Mycobacterium tuberculosis. Mol. Microbiol. 51: 359-370. http://dx. doi. org/10. 1046/j. 1365-2958. 2003. 03844. x.
39. Hsu T, Hingley-Wilson SM, Chen B, Chen M, Dai AZ, Morin PM, Marks CB, Padiyar J, Goulding C, Gingery M, Eisenberg D, Russell RG, Derrick SC, Collins FM, Morris SL, King CH, Jacobs WR, Jr. 2003. The primary mechanism of attenuation of bacillus Calmette-Guerin is a loss of secreted lytic function required for invasion of lung interstitial tissue. Proc. Natl. Acad. Sci. U. S. A. 100: 12420-12425. http://dx. doi. org/10. 1073/pnas. 1635213100.
40. Stanley SA, Raghavan S, Hwang WW, Cox JS. 2003. Acute infection and macrophage subversion by Mycobacterium tuberculosis require a specialized secretion system. Proc. Natl. Acad. Sci. U. S. A. 100:-13001-13006. http://dx. doi. org/10. 1073/pnas. 2235593100.
41. Ohol YM, Goetz DH, Chan K, Shiloh MU, Craik CS, Cox JS. 2010. Mycobacterium tuberculosis MycP1 protease plays a dual role in regulation of ESX-1 secretion and virulence. Cell Host Microbe 7: 210-220. http://dx. doi. org/10. 1016/j. chom. 2010. 02. 006.
42. Bottai D, Majlessi L, Simeone R, Frigui W, Laurent C, Lenormand P, Chen J, Rosenkrands I, Huerre M, Leclerc C, Cole ST, Brosch R. 2011. ESAT-6 secretion-independent impact of ESX-1 genes espF and espG1 on virulence of Mycobacterium tuberculosis. J. Infect. Dis. 203: 1155-1164. http://dx. doi. org/10. 1093/infdis/jiq089.
43. Garces A, Atmakuri K, Chase MR, Woodworth JS, Krastins B, Rothchild AC, Ramsdell TL, Lopez MF, Behar SM, Sarracino DA, Fortune SM. 2010. EspA acts as a critical mediator of ESX1-dependent virulence in Mycobacterium tuberculosis by affecting bacterial cell wall integrity. PLoS Pathog. 6: e1000957. http://dx. doi. org/10. 1371/journal. ppat. 1000957.
44. Chen JM, Zhang M, Rybniker J, Basterra L, Dhar N, Tischler AD, Pojer F, Cole ST. 2013. Phenotypic profiling of Mycobacterium tuberculosis EspA point mutants reveals blockage of ESAT-6 and CFP-10 secretion in vitro does not always correlate with attenuation of virulence. J. Bacteriol. 195: 5421-5430. http://dx. doi. org/10. 1128/JB. 00967-13.
45. Addona TA, Shi X, Keshishian H, Mani DR, Burgess M, Gillette MA, Clauser KR, Shen D, Lewis GD, Farrell LA, Fifer MA, Sabatine MS, Gerszten RE, Carr SA. 2011. A pipeline that integrates the discovery and verification of plasma protein biomarkers reveals candidate markers for cardiovascular disease. Nat. Biotechnol. 29: 635-643. http://dx. doi. org/10. 1038/nbt. 1899.
46. Gillette MA, Carr SA. 2013. Quantitative analysis of peptides and proteins in biomedicine by targeted mass spectrometry. Nat. Methods 10: 28-34. http://dx. doi. org/10. 1038/nmeth. 2309.
47. Griffin JE, Gawronski JD, Dejesus MA, Ioerger TR, Akerley BJ, Sassetti CM. 2011. High-resolution phenotypic profiling defines genes essential for mycobacterial growth and cholesterol catabolism. PLoS Pathog. 7: e1002251. http://dx. doi. org/10. 1371/journal. ppat. 1002251.
48. Zhang YJ, Ioerger TR, Huttenhower C, Long JE, Sassetti CM, Sacchettini JC, Rubin EJ. 2012. Global assessment of genomic regions required for growth in Mycobacterium tuberculosis. PLoS Pathog. 8: e1002946. http://dx. doi. org/10. 1371/journal. ppat. 1002946.
49. Sassetti CM, Rubin EJ. 2003. Genetic requirements for mycobacterial survival during infection. Proc. Natl. Acad. Sci. U. S. A. 100:-12989-12994. http://dx. doi. org/10. 1073/pnas. 2134250100.
50. Wagner JM, Evans TJ, Chen J, Zhu H, Houben EN, Bitter W, Korotkov KV. 2013. Understanding specificity of the mycosin proteases in ESX/type VII secretion by structural and functional analysis. J. Struct. Biol. 184: 115-128. http://dx. doi. org/10. 1016/j. jsb. 2013. 09. 022.
51. Solomonson M, Huesgen PF, Wasney GA, Watanabe N, Gruninger RJ, Prehna G, Overall CM, Strynadka NC. 2013. Structure of the mycosin-1 protease from the mycobacterial ESX-1 protein type VII secretion system. J. Biol. Chem. 288: 17782-17790. http://dx. doi. org/10. 1074/jbc. M113. 462036.
52. McCann JR, McDonough JA, Pavelka MS, Braunstein M. 2007. Betalactamase can function as a reporter of bacterial protein export during Mycobacterium tuberculosis infection of host cells. Microbiology 153: 3350-3359. http://dx. doi. org/10. 1099/mic. 0. 2007/008516-0.
53. Champion MM, Williams EA, Kennedy GM, Champion PA. 2012. Direct detection of bacterial protein secretion using whole colony proteomics. Mol. Cell. Proteomics 11: 596-604. http://dx. doi. org/10. 1074/mcp. M112. 017533.
54. Wei JR, Krishnamoorthy V, Murphy K, Kim JH, Schnappinger D, Alber T, Sassetti CM, Rhee KY, Rubin EJ. 2011. Depletion of antibiotic targets has widely varying effects on growth. Proc. Natl. Acad. Sci. U. S. A. 108: 4176-4181. http://dx. doi. org/10. 1073/pnas. 1018301108.
55. Bottai D, Di Luca M, Majlessi L, Frigui W, Simeone R, Sayes F, Bitter W, Brennan MJ, Leclerc C, Batoni G, Campa M, Brosch R, Esin S. 2012. 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. 83: 1195-1209. http://dx. doi. org/10. 1111/j. 1365-2958. 2012. 08001. x.
56. Teutschbein J, Schumann G, Möllmann U, Grabley S, Cole ST, Munder T. 2009. A protein linkage map of the ESAT-6 secretion system 1 (ESX-1) of Mycobacterium tuberculosis. Microbiol. Res. 164:-253-259. http://dx. doi. org/10. 1016/j. micres. 2006. 11. 016.
57. Daleke MH, van der Woude AD, Parret AH, Ummels R, de Groot AM, Watson D, Piersma SR, Jiménez CR, Luirink J, Bitter W, Houben EN. 2012. Specific chaperones for the type VII protein secretion pathway. J. Biol. Chem. 287: 31939-31947. http://dx. doi. org/10. 1074/jbc. M112. 397596.
58. Chen JM, Zhang M, Rybniker J, Boy-Röttger S, Dhar N, Pojer F, Cole ST. 2013. Mycobacterium tuberculosis EspB binds phospholipids and mediates EsxA-independent virulence. Mol. Microbiol. 89: 1154-1166. http://dx. doi. org/10. 1111/mmi. 12336.
59. Champion PA, Champion MM, Manzanillo P, Cox JS. 2009. ESX-1 secreted virulence factors are recognized by multiple cytosolic AAA ATPases in pathogenic mycobacteria. Mol. Microbiol. 73: 950-962. http://dx. doi. org/10. 1111/j. 1365-2958. 2009. 06821. x.
60. McLaughlin B, Chon JS, MacGurn JA, Carlsson F, Cheng TL, Cox JS, Brown EJ. 2007. A mycobacterium ESX-1-secreted virulence factor with unique requirements for export. PLoS Pathog. 3: e105. http://dx. doi. org/10. 1371/journal. ppat. 0030105.
61. Houben EN, Bestebroer J, Ummels R, Wilson L, Piersma SR, Jiménez CR, Ottenhoff TH, Luirink J, Bitter W. 2012. Composition of the type VII secretion system membrane complex. Mol. Microbiol. 86:-472-484. http://dx. doi. org/10. 1111/j. 1365-2958. 2012. 08206. x.
62. Festa RA, McAllister F, Pearce MJ, Mintseris J, Burns KE, Gygi SP, Darwin KH. 2010. Prokaryotic ubiquitin-like protein (Pup) proteome of Mycobacterium tuberculosis [corrected]. PLoS One 5: e8589. http://dx. doi. org/10. 1371/journal. pone. 0008589.
63. Farhana A, Kumar S, Rathore SS, Ghosh PC, Ehtesham NZ, Tyagi AK, Hasnain SE. 2008. Mechanistic insights into a novel exporter-importer system of Mycobacterium tuberculosis unravel its role in trafficking of iron. PLoS One 3: e2087. http://dx. doi. org/10. 1371/journal. pone. 0002087.
64. Rodriguez GM, Smith I. 2006. Identification of an ABC transporter required for iron acquisition and virulence in Mycobacterium tuberculosis. J. Bacteriol. 188: 424-430. http://dx. doi. org/10. 1128/JB. 188. 2. 424-430. 2006.
65. Ryndak MB, Wang S, Smith I, Rodriguez GM. 2009. Mycobacterium tuberculosis high affinity iron importer, IrtA, contains an FAD-binding domain. J. Bacteriol. 192: 861-869. http://dx. doi. org/10. 1128/JB. 00223-09.