Chapter 15 : The Physiology and Genetics of Oxidative Stress in Mycobacteria

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

The Physiology and Genetics of Oxidative Stress in Mycobacteria, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818845/9781555818838_Chap15-1.gif /docserver/preview/fulltext/10.1128/9781555818845/9781555818838_Chap15-2.gif


Redox reactions are essential for life and play a role in both aerobic and anaerobic respiration. In aerobic microorganisms, the oxidants and reactive species are equalized by the antioxidants in order to maintain redox balance ( ). is an obligate aerobe, although it has been demonstrated that it can survive for more than a decade under anaerobic conditions. In the macrophage and the lung of the host, is exposed to a range of complex environments which can profoundly influence the physiology, including the redox homeostasis, of the mycobacterium. Thus, it is likely that the mechanisms to maintain redox homeostasis in are vital in determining disease outcome. As in other bacteria, has developed pathways that monitor and respond to gaseous signals, such as NO, CO, and O, and fluctuations in the intra- and extracellular redox status ( ). In this article, we will explore the physiology and genetics of redox homeostasis in mycobacteria by considering the environments to which is exposed, the sensors whereby mycobacteria discern an imbalance in the redox balance both endogenously and in the extracellular environment, mechanisms utilized by mycobacteria to respond to redox stress in order to maintain the intracellular redox balance, and the means currently used to measure the redox state in mycobacteria.

Citation: Cumming B, Lamprecht D, Wells R, Saini V, Mazorodze J, Steyn A. 2014. The Physiology and Genetics of Oxidative Stress in Mycobacteria, p 299-322. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0019-2013
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

The RSH/RSSR reductase/NAD(P)H redox pathway for the reduction of cellular oxidants. The oxidation-reduction reaction of a typical flavoprotein disulfide reductase. The commonly found intracellular low-molecular-weight thiols and the organisms in which they are found.

Citation: Cumming B, Lamprecht D, Wells R, Saini V, Mazorodze J, Steyn A. 2014. The Physiology and Genetics of Oxidative Stress in Mycobacteria, p 299-322. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0019-2013
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

The biosynthesis pathway of mycothiol (MSH), with the related biosynthesis of I-1-P by tbINO. The enzyme associated with MshA2 activity is yet to be identified. The genomic organization of the MSH biosynthetic genes in H37Rv. See text for definition of abbreviations.

Citation: Cumming B, Lamprecht D, Wells R, Saini V, Mazorodze J, Steyn A. 2014. The Physiology and Genetics of Oxidative Stress in Mycobacteria, p 299-322. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0019-2013
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

The intracellular functions of MSH: redox homeostasis, detoxification, source of carbon, and a cofactor in enzyme reactions.

Citation: Cumming B, Lamprecht D, Wells R, Saini V, Mazorodze J, Steyn A. 2014. The Physiology and Genetics of Oxidative Stress in Mycobacteria, p 299-322. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0019-2013
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
Figure 4

Biosynthesis of ergothioneine as proposed by Seebeck ( ). Putative five-gene cluster in H37Rv encoding ERG biosynthetic enzymes.

Citation: Cumming B, Lamprecht D, Wells R, Saini V, Mazorodze J, Steyn A. 2014. The Physiology and Genetics of Oxidative Stress in Mycobacteria, p 299-322. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0019-2013
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Halliwell B,, Gutteridge JMC . 2007. Free Radicals in Biology and Medicine, 4th ed. Oxford University Press, Oxford/New York.
2. Sacchettini JC,, Rubin EJ,, Freundlich JS . 2008. Drugs versus bugs: in pursuit of the persistent predator Mycobacterium tuberculosis. Nat Rev Microbiol 6 : 41 52.[PubMed][CrossRef]
3. Kumar A,, Toledo JC,, Patel RP,, Lancaster JR Jr,, Steyn AJ . 2007. Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor. Proc Natl Acad Sci USA 104 : 11568 11573.[PubMed][CrossRef]
4. Singh A,, Guidry L,, Narasimhulu KV,, Mai D,, Trombley J,, Redding KE,, Giles GI,, Lancaster JR Jr,, Steyn AJ . 2007. Mycobacterium tuberculosis WhiB3 responds to O2 and nitric oxide via its [4Fe-4S] cluster and is essential for nutrient starvation survival. Proc Natl Acad Sci USA 104 : 11562 11567.[PubMed][CrossRef]
5. Schafer FQ,, Buettner GR . 2001. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med 30 : 1191 1212.[CrossRef]
6. Hansen RE,, Roth D,, Winther JR . 2009. Quantifying the global cellular thiol-disulfide status. Proc Natl Acad Sci USA 106 : 422 427.[PubMed][CrossRef]
7. Quemard A,, Sacchettini JC,, Dessen A,, Vilcheze C,, Bittman R,, Jacobs WR Jr,, Blanchard JS . 1995. Enzymatic characterization of the target for isoniazid in Mycobacterium tuberculosis. Biochemistry 34 : 8235 8241.[PubMed][CrossRef]
8. Baulard AR,, Betts JC,, Engohang-Ndong J,, Quan S,, McAdam RA,, Brennan PJ,, Locht C,, Besra GS . 2000. Activation of the pro-drug ethionamide is regulated in mycobacteria. J Biol Chem 275 : 28326 28331.[PubMed]
9. Manjunatha UH,, Boshoff H,, Dowd CS,, Zhang L,, Albert TJ,, Norton JE,, Daniels L,, Dick T,, Pang SS,, Barry CE 3rd . 2006. Identification of a nitroimidazo-oxazine-specific protein involved in PA-824 resistance in Mycobacterium tuberculosis. Proc Natl Acad Sci USA 103 : 431 436.[PubMed][CrossRef]
10. Vilcheze C,, Weisbrod TR,, Chen B,, Kremer L,, Hazbon MH,, Wang F,, Alland D,, Sacchettini JC,, Jacobs WR Jr . 2005. Altered NADH/NAD+ ratio mediates coresistance to isoniazid and ethionamide in mycobacteria. Antimicrob Agents Chemother 49 : 708 720.[PubMed][CrossRef]
11. Miesel L,, Weisbrod TR,, Marcinkeviciene JA,, Bittman R,, Jacobs WR Jr . 1998. NADH dehydrogenase defects confer isoniazid resistance and conditional lethality in Mycobacterium smegmatis. J Bacteriol 180 : 2459 2467.[PubMed]
12. Xu X,, Vilcheze C,, Av-Gay Y,, Gomez-Velasco A,, Jacobs WR Jr . 2011. Precise null deletion mutations of the mycothiol synthesis genes reveal their role in isoniazid and ethionamide resistance in Mycobacterium smegmatis. Antimicrob Agents Chemother 55 : 3133 3139.[PubMed][CrossRef]
13. Bedard K,, Krause KH . 2007. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87 : 245 313.[PubMed][CrossRef]
14. Chan J,, Xing Y,, Magliozzo RS,, Bloom BR . 1992. Killing of virulent Mycobacterium tuberculosis by reactive nitrogen intermediates produced by activated murine macrophages. J Exp Med 175 : 1111 1122.[PubMed][CrossRef]
15. Chan J,, Tanaka K,, Carroll D,, Flynn J,, Bloom BR . 1995. Effects of nitric oxide synthase inhibitors on murine infection with Mycobacterium tuberculosis. Infect Immun 63 : 736 740.[PubMed]
16. Styblo K . 1980. Recent advances in epidemiological research in tuberculosis. Adv Tuberc Res 20 : 1 63.[PubMed]
17. DePalo VA,, McCool FD, . 2003. Pulmonary anatomy & physiology. In Hanley ME,, Welsh CH (ed), Current Diagnosis & Treatment in Pulmonary Medicine. McGraw-Hill, New York, NY.
18. Park HS,, Kim SR,, Lee YC . 2009. Impact of oxidative stress on lung diseases. Respirology 14 : 2 38.[PubMed][CrossRef]
19. Ward PA . 2010. Oxidative stress: acute and progressive lung injury. Ann NY Acad Sci 1203 : 53 59.[PubMed][CrossRef]
20. Rahman I,, Biswas SK,, Kode A . 2006. Oxidant and antioxidant balance in the airways and airway diseases. Eur J Pharmacol 533 : 222 239.[PubMed][CrossRef]
21. Liang Y,, Yeligar SM,, Brown LA . 2012. Chronic-alcohol-abuse-induced oxidative stress in the development of acute respiratory distress syndrome. Sci World J 2012 : 740308. [PubMed][CrossRef]
22. Buhl R,, Jaffe HA,, Holroyd KJ,, Wells FB,, Mastrangeli A,, Saltini C,, Cantin AM,, Crystal RG . 1989. Systemic glutathione deficiency in symptom-free HIV-seropositive individuals. Lancet 2 : 1294 1298.[CrossRef]
23. Narasimhan P,, Wood J,, Macintyre CR,, Mathai D . 2013. Risk factors for tuberculosis. Pulm Med 2013 : 828939. [PubMed][CrossRef]
24. Yeh MY,, Burnham EL,, Moss M,, Brown LA . 2008. Non-invasive evaluation of pulmonary glutathione in the exhaled breath condensate of otherwise healthy alcoholics. Respir Med 102 : 248 255.[PubMed][CrossRef]
25. Venketaraman V,, Millman A,, Salman M,, Swaminathan S,, Goetz M,, Lardizabal A,, David H,, Connell ND . 2008. Glutathione levels and immune responses in tuberculosis patients. Microb Pathog 44 : 255 261.[PubMed][CrossRef]
26. Vandiviere HM,, Loring WE,, Melvin I,, Willis S . 1956. The treated pulmonary lesion and its tubercle bacillus. II. The death and resurrection. Am J Med Sci 232 : 30 37; passim.[PubMed][CrossRef]
27. Wayne LG,, Hayes LG . 1996. An in vitro model for sequential study of shiftdown of Mycobacterium tuberculosis through two stages of nonreplicating persistence. Infect Immun 64 : 2062 2069.[PubMed]
28. Meylan PR,, Richman DD,, Kornbluth RS . 1992. Reduced intracellular growth of mycobacteria in human macrophages cultivated at physiologic oxygen pressure. Am Rev Respir Dis 145 : 947 953.[PubMed][CrossRef]
29. Boshoff HI,, Barry CE 3rd . 2005. Tuberculosis: metabolism and respiration in the absence of growth. Nat Rev Microbiol 3 : 70 80.[PubMed][CrossRef]
30. Via LE,, Lin PL,, Ray SM,, Carrillo J,, Allen SS,, Eum SY,, Taylor K,, Klein E,, Manjunatha U,, Gonzales J,, Lee EG,, Park SK,, Raleigh JA,, Cho SN,, McMurray DN,, Flynn JL,, Barry CE 3rd . 2008. Tuberculous granulomas are hypoxic in guinea pigs, rabbits, and nonhuman primates. Infect Immun 76 : 2333 2340.[PubMed][CrossRef]
31. Leistikow RL,, Morton RA,, Bartek IL,, Frimpong I,, Wagner K,, Voskuil MI . 2010. The Mycobacterium tuberculosis DosR regulon assists in metabolic homeostasis and enables rapid recovery from nonrespiring dormancy. J Bacteriol 192 : 1662 1670.[PubMed][CrossRef]
32. Dasgupta N,, Kapur V,, Singh KK,, Das TK,, Sachdeva S,, Jyothisri K,, Tyagi JS . 2000. Characterization of a two-component system, devR-devS, of Mycobacterium tuberculosis. Tuber Lung Dis 80 : 141 159.[PubMed][CrossRef]
33. Kumar A,, Deshane JS,, Crossman DK,, Bolisetty S,, Yan BS,, Kramnik I,, Agarwal A,, Steyn AJ . 2008. Heme oxygenase-1-derived carbon monoxide induces the Mycobacterium tuberculosis dormancy regulon. J Biol Chem 283 : 18032 18039.[PubMed][CrossRef]
34. Shiloh MU,, Manzanillo P,, Cox JS . 2008. Mycobacterium tuberculosis senses host-derived carbon monoxide during macrophage infection. Cell Host Microbe 3 : 323 330.[PubMed][CrossRef]
35. Ioanoviciu A,, Yukl ET,, Moenne-Loccoz P,, de Montellano PR . 2007. DevS, a heme-containing two-component oxygen sensor of Mycobacterium tuberculosis. Biochemistry 46 : 4250 4260.[PubMed][CrossRef]
36. Sousa EH,, Tuckerman JR,, Gonzalez G,, Gilles-Gonzalez MA . 2007. DosT and DevS are oxygen-switched kinases in Mycobacterium tuberculosis. Protein Sci 16 : 1708 1719.[PubMed][CrossRef]
37. Kumar A,, Toledo JC,, Patel RP,, Lancaster JR Jr,, Steyn AJ . 2007. Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor. Proc Natl Acad Sci USA 104 : 11568 11573.[PubMed][CrossRef]
38. Singh A,, Guidry L,, Narasimhulu KV,, Mai D,, Trombley J,, Redding KE,, Giles GI,, Lancaster JR Jr,, Steyn AJ . 2007. Mycobacterium tuberculosis WhiB3 responds to O2 and nitric oxide via its [4Fe-4S] cluster and is essential for nutrient starvation survival. Proc Natl Acad Sci USA 104 : 11562 11567.[PubMed][CrossRef]
39. Soliveri JA,, Gomez J,, Bishai WR,, Chater KF . 2000. Multiple paralogous genes related to the Streptomyces coelicolor developmental regulatory gene whiB are present in Streptomyces and other actinomycetes. Microbiology 146 : 333 343.[PubMed]
40. Steyn AJ,, Collins DM,, Hondalus MK,, Jacobs WR Jr,, Kawakami RP,, Bloom BR . 2002. Mycobacterium tuberculosis WhiB3 interacts with RpoV to affect host survival but is dispensable for in vivo growth. Proc Natl Acad Sci USA 99 : 3147 3152.[PubMed][CrossRef]
41. Kim TH,, Park JS,, Kim HJ,, Kim Y,, Kim P,, Lee HS . 2005. The whcE gene of Corynebacterium glutamicum is important for survival following heat and oxidative stress. Biochem Biophys Res Commun 337 : 757 764.[PubMed][CrossRef]
42. Morris RP,, Nguyen L,, Gatfield J,, Visconti K,, Nguyen K,, Schnappinger D,, Ehrt S,, Liu Y,, Heifets L,, Pieters J,, Schoolnik G,, Thompson CJ . 2005. Ancestral antibiotic resistance in Mycobacterium tuberculosis. Proc Natl Acad Sci USA 102 : 12200 12205.[PubMed][CrossRef]
43. Larsson C,, Luna B,, Ammerman NC,, Maiga M,, Agarwal N,, Bishai WR . 2012. Gene expression of Mycobacterium tuberculosis putative transcription factors whiB1-7 in redox environments. PLoS One 7 : e37516. [PubMed][CrossRef]
44. Singh A,, Crossman DK,, Mai D,, Guidry L,, Voskuil MI,, Renfrow MB,, Steyn AJ . 2009. Mycobacterium tuberculosis WhiB3 maintains redox homeostasis by regulating virulence lipid anabolism to modulate macrophage response. PLoS Pathog 5 : e1000545. [PubMed][CrossRef]
45. Sherman DR,, Voskuil M,, Schnappinger D,, Liao R,, Harrell MI,, Schoolnik GK . 2001. Regulation of the Mycobacterium tuberculosis hypoxic response gene encoding alpha-crystallin. Proc Natl Acad Sci USA 98 : 7534 7539.[PubMed][CrossRef]
46. Ohno H,, Zhu G,, Mohan VP,, Chu D,, Kohno S,, Jacobs WR Jr,, Chan J . 2003. The effects of reactive nitrogen intermediates on gene expression in Mycobacterium tuberculosis. Cell Microbiol 5 : 637 648.[PubMed][CrossRef]
47. Voskuil MI,, Visconti KC,, Schoolnik GK . 2004. Mycobacterium tuberculosis gene expression during adaptation to stationary phase and low-oxygen dormancy. Tuberculosis (Edinb) 84 : 218 227.[PubMed][CrossRef]
48. Betts JC,, Lukey PT,, Robb LC,, McAdam RA,, Duncan K . 2002. Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol Microbiol 43 : 717 731.[PubMed][CrossRef]
49. Rustad TR,, Harrell MI,, Liao R,, Sherman DR . 2008. The enduring hypoxic response of Mycobacterium tuberculosis. PLoS One 3 : e1502. [PubMed][CrossRef]
50. Rachman H,, Strong M,, Schaible U,, Schuchhardt J,, Hagens K,, Mollenkopf H,, Eisenberg D,, Kaufmann SH . 2006. Mycobacterium tuberculosis gene expression profiling within the context of protein networks. Microbes Infect 8 : 747 757.[PubMed][CrossRef]
51. Chawla M,, Parikh P,, Saxena A,, Munshi M,, Mehta M,, Mai D,, Srivastava AK,, Narasimhulu KV,, Redding KE,, Vashi N,, Kumar D,, Steyn AJ,, Singh A . 2012. Mycobacterium tuberculosis WhiB4 regulates oxidative stress response to modulate survival and dissemination in vivo. Mol Microbiol 85 : 1148 1165.[PubMed][CrossRef]
52. Boshoff HI,, Xu X,, Tahlan K,, Dowd CS,, Pethe K,, Camacho LR,, Park TH,, Yun CS,, Schnappinger D,, Ehrt S,, Williams KJ,, Barry CE 3rd . 2008. Biosynthesis and recycling of nicotinamide cofactors in Mycobacterium tuberculosis. An essential role for NAD in nonreplicating bacilli. J Biol Chem 283 : 19329 19341.[PubMed][CrossRef]
53. Burian J,, Ramon-Garcia S,, Howes CG,, Thompson CJ . 2012. WhiB7, a transcriptional activator that coordinates physiology with intrinsic drug resistance in Mycobacterium tuberculosis. Expert Rev Anti Infect Ther 10 : 1037 1047.[PubMed][CrossRef]
54. Aslund F,, Beckwith J . 1999. Bridge over troubled waters: sensing stress by disulfide bond formation. Cell 96 : 751 753.[CrossRef]
55. Voskuil MI,, Bartek IL,, Visconti K,, Schoolnik GK . 2011. The response of Mycobacterium tuberculosis to reactive oxygen and nitrogen species. Front Microbiol 2 : 105. [PubMed]
56. Humpel A,, Gebhard S,, Cook GM,, Berney M . 2010. The SigF regulon in Mycobacterium smegmatis reveals roles in adaptation to stationary phase, heat, and oxidative stress. J Bacteriol 192 : 2491 2502.[PubMed][CrossRef]
57. Hahn MY,, Raman S,, Anaya M,, Husson RN . 2005. The Mycobacterium tuberculosis extracytoplasmic-function sigma factor SigL regulates polyketide synthases and secreted or membrane proteins and is required for virulence. J Bacteriol 187 : 7062 7071.[PubMed][CrossRef]
58. Thakur KG,, Praveena T,, Gopal B . 2010. Structural and biochemical bases for the redox sensitivity of Mycobacterium tuberculosis RslA. J Mol Biol 397 : 1199 1208.[PubMed][CrossRef]
59. Song T,, Dove SL,, Lee KH,, Husson RN . 2003. RshA, an anti-sigma factor that regulates the activity of the mycobacterial stress response sigma factor SigH. Mol Microbiol 50 : 949 959.[PubMed][CrossRef]
60. Barik S,, Sureka K,, Mukherjee P,, Basu J,, Kundu M . 2010. RseA, the SigE specific anti-sigma factor of Mycobacterium tuberculosis, is inactivated by phosphorylation-dependent ClpC1P2 proteolysis. Mol Microbiol 75 : 592 606.[PubMed][CrossRef]
61. Li W,, Bottrill AR,, Bibb MJ,, Buttner MJ,, Paget MS,, Kleanthous C . 2003. The role of zinc in the disulphide stress-regulated anti-sigma factor RsrA from Streptomyces coelicolor. J Mol Biol 333 : 461 472.[PubMed][CrossRef]
62. Paget MS,, Bae JB,, Hahn MY,, Li W,, Kleanthous C,, Roe JH,, Buttner MJ . 2001. Mutational analysis of RsrA, a zinc-binding anti-sigma factor with a thiol-disulphide redox switch. Mol Microbiol 39 : 1036 1047.[PubMed][CrossRef]
63. Brugarolas P,, Movahedzadeh F,, Wang Y,, Zhang N,, Bartek IL,, Gao Y,, Voskuil MI,, Franzblau SG,, He C . 2012. The oxidation-sensing regulator (MosR) is a new redox-dependent transcription factor in Mycobacterium tuberculosis. J Biol Chem 287 : 37703 37712.[PubMed][CrossRef]
64. Rengarajan J,, Bloom BR,, Rubin EJ . 2005. Genome-wide requirements for Mycobacterium tuberculosis adaptation and survival in macrophages. Proc Natl Acad Sci USA 102 : 8327 8332.[PubMed][CrossRef]
65. Chan J,, Fujiwara T,, Brennan P,, McNeil M,, Turco SJ,, Sibille JC,, Snapper M,, Aisen P,, Bloom BR . 1989. Microbial glycolipids: possible virulence factors that scavenge oxygen radicals. Proc Natl Acad Sci USA 86 : 2453 2457.[PubMed][CrossRef]
66. Chan J,, Fan XD,, Hunter SW,, Brennan PJ,, Bloom BR . 1991. Lipoarabinomannan, a possible virulence factor involved in persistence of Mycobacterium tuberculosis within macrophages. Infect Immun 59 : 1755 1761.[PubMed]
67. Pabst MJ,, Gross JM,, Brozna JP,, Goren MB . 1988. Inhibition of macrophage priming by sulfatide from Mycobacterium tuberculosis. J Immunol 140 : 634 640.[PubMed]
68. Miller BH,, Fratti RA,, Poschet JF,, Timmins GS,, Master SS,, Burgos M,, Marletta MA,, Deretic V . 2004. Mycobacteria inhibit nitric oxide synthase recruitment to phagosomes during macrophage infection. Infect Immun 72 : 2872 2878.[PubMed][CrossRef]
69. Davis AS,, Vergne I,, Master SS,, Kyei GB,, Chua J,, Deretic V . 2007. Mechanism of inducible nitric oxide synthase exclusion from mycobacterial phagosomes. PLoS Pathog 3 : e186. [PubMed][CrossRef]
70. El Kasmi KC,, Qualls JE,, Pesce JT,, Smith AM,, Thompson RW,, Henao-Tamayo M,, Basaraba RJ,, Konig T,, Schleicher U,, Koo MS,, Kaplan G,, Fitzgerald KA,, Tuomanen EI,, Orme IM,, Kanneganti TD,, Bogdan C,, Wynn TA,, Murray PJ . 2008. Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens. Nat Immunol 9 : 1399 1406.[PubMed][CrossRef]
71. Qualls JE,, Neale G,, Smith AM,, Koo MS,, DeFreitas AA,, Zhang H,, Kaplan G,, Watowich SS,, Murray PJ . 2010. Arginine usage in mycobacteria-infected macrophages depends on autocrine-paracrine cytokine signaling. Sci Signal 3 : ra62. [PubMed][CrossRef]
72. Pessanha AP,, Martins RA,, Mattos-Guaraldi AL,, Vianna A,, Moreira LO . 2012. Arginase-1 expression in granulomas of tuberculosis patients. FEMS Immunol Med Microbiol 66 : 265 268.[PubMed][CrossRef]
73. Andersen P,, Askgaard D,, Ljungqvist L,, Bennedsen J,, Heron I . 1991. Proteins released from Mycobacterium tuberculosis during growth. Infect Immun 59 : 1905 1910.[PubMed]
74. Zhang Y,, Lathigra R,, Garbe T,, Catty D,, Young D . 1991. Genetic analysis of superoxide dismutase, the 23 kilodalton antigen of Mycobacterium tuberculosis. Mol Microbiol 5 : 381 391.[PubMed][CrossRef]
75. Harth G,, Horwitz MA . 1999. Export of recombinant Mycobacterium tuberculosis superoxide dismutase is dependent upon both information in the protein and mycobacterial export machinery. A model for studying export of leaderless proteins by pathogenic mycobacteria. J Biol Chem 274 : 4281 4292.[PubMed][CrossRef]
76. Braunstein M,, Espinosa BJ,, Chan J,, Belisle JT,, Jacobs WR Jr . 2003. SecA2 functions in the secretion of superoxide dismutase A and in the virulence of Mycobacterium tuberculosis. Mol Microbiol 48 : 453 464.[PubMed][CrossRef]
77. Battistoni A . 2003. Role of prokaryotic Cu,Zn superoxide dismutase in pathogenesis. Biochem Soc Trans 31 : 1326 1329.[PubMed][CrossRef]
78. Wu CH,, Tsai-Wu JJ,, Huang YT,, Lin CY,, Lioua GG,, Lee FJ . 1998. Identification and subcellular localization of a novel Cu,Zn superoxide dismutase of Mycobacterium tuberculosis. FEBS Lett 439 : 192 196.[CrossRef]
79. Piddington DL,, Fang FC,, Laessig T,, Cooper AM,, Orme IM,, Buchmeier NA . 2001. Cu,Zn superoxide dismutase of Mycobacterium tuberculosis contributes to survival in activated macrophages that are generating an oxidative burst. Infect Immun 69 : 4980 4987.[PubMed][CrossRef]
80. Claiborne A,, Malinowski DP,, Fridovich I . 1979. Purification and characterization of hydroperoxidase II of Escherichia coli B. J Biol Chem 254 : 11664 11668.[PubMed]
81. Diaz GA,, Wayne LG . 1974. Isolation and characterization of catalase produced by Mycobacterium tuberculosis. Am Rev Respir Dis 110 : 312 319.[PubMed]
82. Wengenack NL,, Jensen MP,, Rusnak F,, Stern MK . 1999. Mycobacterium tuberculosis KatG is a peroxynitritase. Biochem Biophys Res Commun 256 : 485 487.[PubMed][CrossRef]
83. Li Z,, Kelley C,, Collins F,, Rouse D,, Morris S . 1998. Expression of katG in Mycobacterium tuberculosis is associated with its growth and persistence in mice and guinea pigs. J Infect Dis 177 : 1030 1035.[PubMed][CrossRef]
84. Nachamkin I,, Kang C,, Weinstein MP . 1997. Detection of resistance to isoniazid, rifampin, and streptomycin in clinical isolates of Mycobacterium tuberculosis by molecular methods. Clin Infect Dis 24 : 894 900.[PubMed][CrossRef]
85. van Soolingen D,, de Haas PE,, van Doorn HR,, Kuijper E,, Rinder H,, Borgdorff MW . 2000. Mutations at amino acid position 315 of the katG gene are associated with high-level resistance to isoniazid, other drug resistance, and successful transmission of Mycobacterium tuberculosis in the Netherlands. J Infect Dis 182 : 1788 1790.[PubMed][CrossRef]
86. Wilson M,, DeRisi J,, Kristensen HH,, Imboden P,, Rane S,, Brown PO,, Schoolnik GK . 1999. Exploring drug-induced alterations in gene expression in Mycobacterium tuberculosis by microarray hybridization. Proc Natl Acad Sci USA 96 : 12833 12838.[PubMed][CrossRef]
87. Wilson TM,, Collins DM . 1996. ahpC, a gene involved in isoniazid resistance of the Mycobacterium tuberculosis complex. Mol Microbiol 19 : 1025 1034.[PubMed][CrossRef]
88. Master SS,, Springer B,, Sander P,, Boettger EC,, Deretic V,, Timmins GS . 2002. Oxidative stress response genes in Mycobacterium tuberculosis: role of ahpC in resistance to peroxynitrite and stage-specific survival in macrophages. Microbiology 148 : 3139 3144.[PubMed]
89. Zhang Z,, Hillas PJ,, Ortiz de Montellano PR . 1999. Reduction of peroxides and dinitrobenzenes by Mycobacterium tuberculosis thioredoxin and thioredoxin reductase. Arch Biochem Biophys 363 : 19 26.[PubMed][CrossRef]
90. Bryk R,, Lima CD,, Erdjument-Bromage H,, Tempst P,, Nathan C . 2002. Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein. Science 295 : 1073 1077.[PubMed][CrossRef]
91. Cole ST,, Brosch R,, Parkhill J,, Garnier T,, Churcher C,, Harris D,, Gordon SV,, Eiglmeier K,, Gas S,, Barry CE 3rd,, 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,, Barrell BG . 1998. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393 : 537 544.[PubMed][CrossRef]
92. Jaeger T . 2007. Peroxiredoxin systems in mycobacteria. Subcell Biochem 44 : 207 217.[PubMed][CrossRef]
93. Holmgren A . 1985. Thioredoxin. Annu Rev Biochem 54 : 237 271.[PubMed][CrossRef]
94. Martin JL . 1995. Thioredoxin: a fold for all reasons. Structure 3 : 245 250.[CrossRef]
95. Williams CH Jr . 1995. Mechanism and structure of thioredoxin reductase from Escherichia coli. FASEB J 9 : 1267 1276.[PubMed]
96. Kadokura H,, Katzen F,, Beckwith J . 2003. Protein disulfide bond formation in prokaryotes. Annu Rev Biochem 72 : 111 135.[PubMed][CrossRef]
97. Akif M,, Khare G,, Tyagi AK,, Mande SC,, Sardesai AA . 2008. Functional studies of multiple thioredoxins from Mycobacterium tuberculosis. J Bacteriol 190 : 7087 7095.[PubMed][CrossRef]
98. Wittenberg JB,, Bolognesi M,, Wittenberg BA,, Guertin M . 2002. Truncated hemoglobins: a new family of hemoglobins widely distributed in bacteria, unicellular eukaryotes, and plants. J Biol Chem 277 : 871 874.[PubMed][CrossRef]
99. Ouellet H,, Ranguelova K,, Labarre M,, Wittenberg JB,, Wittenberg BA,, Magliozzo RS,, Guertin M . 2007. Reaction of Mycobacterium tuberculosis truncated hemoglobin O with hydrogen peroxide: evidence for peroxidatic activity and formation of protein-based radicals. J Biol Chem 282 : 7491 7503.[PubMed][CrossRef]
100. Ascenzi P,, Visca P . 2008. Scavenging of reactive nitrogen species by mycobacterial truncated hemoglobins. Methods Enzymol 436 : 317 337.[CrossRef]
101. Nicoletti FP,, Comandini A,, Bonamore A,, Boechi L,, Boubeta FM,, Feis A,, Smulevich G,, Boffi A . 2010. Sulfide binding properties of truncated hemoglobins. Biochemistry 49 : 2269 2278.[PubMed][CrossRef]
102. Wheeler PR,, Coldham NG,, Keating L,, Gordon SV,, Wooff EE,, Parish T,, Hewinson RG . 2005. Functional demonstration of reverse transsulfuration in the Mycobacterium tuberculosis complex reveals that methionine is the preferred sulfur source for pathogenic mycobacteria. J Biol Chem 280 : 8069 8078.[PubMed][CrossRef]
103. Weissbach H,, Etienne F,, Hoshi T,, Heinemann SH,, Lowther WT,, Matthews B,, St John G,, Nathan C,, Brot N . 2002. Peptide methionine sulfoxide reductase: structure, mechanism of action, and biological function. Arch Biochem Biophys 397 : 172 178.[PubMed][CrossRef]
104. Rhee KY,, Erdjument-Bromage H,, Tempst P,, Nathan CF . 2005. S-nitroso proteome of Mycobacterium tuberculosis: enzymes of intermediary metabolism and antioxidant defense. Proc Natl Acad Sci USA 102 : 467 472.[PubMed][CrossRef]
105. St John G,, Brot N,, Ruan J,, Erdjument-Bromage H,, Tempst P,, Weissbach H,, Nathan C . 2001. Peptide methionine sulfoxide reductase from Escherichia coli and Mycobacterium tuberculosis protects bacteria against oxidative damage from reactive nitrogen intermediates. Proc Natl Acad Sci USA 98 : 9901 9906.[PubMed][CrossRef]
106. Boschi-Muller S,, Olry A,, Antoine M,, Branlant G . 2005. The enzymology and biochemistry of methionine sulfoxide reductases. Biochim Biophys Acta 1703 : 231 238.[PubMed][CrossRef]
107. Lee WL,, Gold B,, Darby C,, Brot N,, Jiang X,, de Carvalho LP,, Wellner D,, St John G,, Jacobs WR Jr,, Nathan C . 2009. Mycobacterium tuberculosis expresses methionine sulphoxide reductases A and B that protect from killing by nitrite and hypochlorite. Mol Microbiol 71 : 583 593.[PubMed][CrossRef]
108. Douglas T,, Daniel DS,, Parida BK,, Jagannath C,, Dhandayuthapani S . 2004. Methionine sulfoxide reductase A (MsrA) deficiency affects the survival of Mycobacterium smegmatis within macrophages. J Bacteriol 186 : 3590 3598.[PubMed][CrossRef]
109. Schnappinger D,, Ehrt S,, Voskuil MI,, Liu Y,, Mangan JA,, Monahan IM,, Dolganov G,, Efron B,, Butcher PD,, Nathan C,, Schoolnik GK . 2003. Transcriptional adaptation of Mycobacterium tuberculosis within macrophages: insights into the phagosomal environment. J Exp Med 198 : 693 704.[PubMed][CrossRef]
110. Fahey RC . 2001. Novel thiols of prokaryotes. Annu Rev Microbiol 55 : 333 356.[PubMed][CrossRef]
111. Patel MP,, Blanchard JS . 1998. Synthesis of Des-myo-Inositol mycothiol and demonstration of a mycobacterial specific reductase activity. J Am Chem Soc 120 : 11538 11539.[CrossRef]
112. Wong KK,, Vanoni MA,, Blanchard JS . 1988. Glutathione reductase: solvent equilibrium and kinetic isotope effects. Biochemistry 27 : 7091 7096.[PubMed][CrossRef]
113. del Cardayre SB,, Stock KP,, Newton GL,, Fahey RC,, Davies JE . 1998. Coenzyme A disulfide reductase, the primary low molecular weight disulfide reductase from Staphylococcus aureus. Purification and characterization of the native enzyme. J Biol Chem 273 : 5744 5751.[CrossRef]
114. Gaballa A,, Newton GL,, Antelmann H,, Parsonage D,, Upton H,, Rawat M,, Claiborne A,, Fahey RC,, Helmann JD . 2010. Biosynthesis and functions of bacillithiol, a major low-molecular-weight thiol in bacilli. Proc Natl Acad Sci USA 107 : 6482 6486.[PubMed][CrossRef]
115. Antelmann H,, Hamilton CJ . 2012. Bacterial mechanisms of reversible protein S-thiolation: structural and mechanistic insights into mycoredoxins. Mol Microbiol 86 : 759 764.[PubMed][CrossRef]
116. Krauth-Siegel RL,, Comini MA . 2008. Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism. Biochim Biophys Acta 1780 : 1236 1248.[PubMed][CrossRef]
117. Gutierrez-Lugo M-T,, Newton GL,, Fahey RC,, Bewley CA . 2006. Cloning, expression and rapid purification of active recombinant mycothiol ligase as B1 immunoglobulin binding domain of streptococcal protein G, glutathione-S-transferase and maltose binding protein fusion proteins in Mycobacterium smegmatis. Protein Expr Purif 50 : 128 136.[PubMed][CrossRef]
118. Newton GL,, Leung SS,, Wakabayashi JI,, Rawat M,, Fahey RC . 2011. The DinB superfamily includes novel mycothiol, bacillithiol, and glutathione S-transferases. Biochemistry 50 : 10751 10760.[PubMed][CrossRef]
119. Cheah IK,, Halliwell B . 2012. Ergothioneine: antioxidant potential, physiological function and role in disease. Biochim Biophys Acta 1822 : 784 793.[PubMed][CrossRef]
120. Banerjee R . 2012. Redox outside the box: linking extracellular redox remodeling with intracellular redox metabolism. J Biol Chem 287 : 4397 4402.[PubMed][CrossRef]
121. Benetti LR,, Campos D,, Gurgueira SA,, Vercesi AE,, Guedes CEV,, Santos KL,, Wallace JL,, Teixeira SA,, Florenzano J,, Costa SKP,, Muscara MN,, Ferreira HHA . 2013. Hydrogen sulfide inhibits oxidative stress in lungs from allergic mice in vivo. Eur J Pharmacol 698 : 463 469.[PubMed][CrossRef]
122. Parasassi T,, Brunelli R,, Costa G,, De Spirito M,, Krasnowska E,, Lundeberg T,, Pittaluga E,, Ursini F . 2010. Thiol redox transitions in cell signaling: a lesson from N-acetylcysteine. Sci World J 10 : 1192 1202.[PubMed][CrossRef]
123. Garcia-Mata C,, Lamattina L . 2013. Gasotransmitters are emerging as new guard cell signaling molecules and regulators of leaf gas exchange. Plant Sci 201-202 : 66 73.[PubMed][CrossRef]
124. Newton GL,, Arnold K,, Price MS,, Sherrill C,, Delcardayre SB,, Aharonowitz Y,, Cohen G,, Davies J,, Fahey RC,, Davis C . 1996. Distribution of thiols in microorganisms: mycothiol is a major thiol in most actinomycetes. J Bacteriol 178 : 1990 1995.[PubMed]
125. Newton GL,, Fahey RC,, Cohen G,, Aharonowitz Y . 1993. Low-molecular-weight thiols in streptomycetes and their potential role as antioxidants. J Bacteriol 175 : 2734 2742.[PubMed]
126. Sakuda S,, Zhou Z-Y,, Yamada Y . 1994. Structure of a novel disulfide of 2-(N-acetylcysteinyl)amido-2-deoxy-alpha-D-glucopyran-osyl-myo-inositol produced by Streptomyces sp. Biosci Biotechnol Biochem 58 : 1347 1348.[PubMed][CrossRef]
127. Spies HSC,, Steenkamp DJ . 1994. Thiols of intracellular pathogens. Identification of ovothiol A in Leishmania donovani and structural analysis of a novel thiol from Mycobacterium bovis. Eur J Biochem 224 : 203 213.[PubMed][CrossRef]
128. Newton GL,, Bewley CA,, Dwyer TJ,, Horn R,, Aharonowitz Y,, Cohen G,, Davies J,, Faulkner DJ,, Fahey RC . 1995. The structure of U17 isolated from Streptomyces clavuligerus and its properties as an antioxidant thiol. Eur J Biochem 230 : 821 825.[PubMed][CrossRef]
129. Norman RA,, McAlister MSB,, Murray-Rust J,, Movahedzadeh F,, Stoker NG,, McDonald NQ . 2002. Crystal structure of inositol 1-phosphate synthase from Mycobacterium tuberculosis, a key enzyme in phosphatidylinositol synthesis. Structure 10 : 393 402.[CrossRef]
130. Morita YS,, Fukuda T,, Sena CBC,, Yamaryo-Botte Y,, McConville MJ,, Kinoshita T . 2011. Inositol lipid metabolism in mycobacteria: biosynthesis and regulatory mechanisms. Biochim Biophys Acta 1810 : 630 641.[PubMed][CrossRef]
131. Newton GL,, Koledin T,, Gorovitz B,, Rawat M,, Fahey RC,, Av-Gay Y . 2003. The glycosyltransferase gene encoding the enzyme catalyzing the first step of mycothiol biosynthesis (mshA). J Bacteriol 185 : 3476 3479.[PubMed][CrossRef]
132. Newton GL,, Ta P,, Bzymek KP,, Fahey RC . 2006. Biochemistry of the initial steps of mycothiol biosynthesis. J Biol Chem 281 : 33910 33920.[PubMed][CrossRef]
133. Newton GL,, Av-Gay Y,, Fahey RC . 2000. N-Acetyl-1- D-myo-inosityl-2-amino-2-deoxy-α- D-glucopyranoside deacetylase (MshB) is a key enzyme in mycothiol biosynthesis. J Bacteriol 182 : 6958 6963.[PubMed][CrossRef]
134. Newton GL,, Ko M,, Ta P,, Av-Gay Y,, Fahey RC . 2006. Purification and characterization of Mycobacterium tuberculosis 1D-myo-inosityl-2-acetamido-2-deoxy-a-D-glucopyranoside deacetylase, MshB, a mycothiol biosynthetic enzyme. Protein Expr Purif 47 : 542 550.[PubMed][CrossRef]
135. Huang X,, Kocabas E,, Hernick M . 2011. The activity and cofactor preferences of N-acetyl-1-D-myo-inositol-2-amino-2-deoxy-α-D-glucopyranoside deacetylase (MshB) change depending on environmental conditions. J Biol Chem 286( 23) : 20275 20282.[PubMed][CrossRef]
136. Fan F,, Blanchard JS . 2009. Toward the catalytic mechanism of a cysteine ligase (MshC) from Mycobacterium smegmatis: an enzyme involved in the biosynthetic pathway of mycothiol. Biochemistry 48 : 7150 7159.[PubMed][CrossRef]
137. Fan F,, Luxenburger A,, Painter GF,, Blanchard JS . 2007. Steady-state and pre-steady-state kinetic analysis of Mycobacterium smegmatis cysteine ligase (MshC). Biochemistry 46 : 11421 11429.[PubMed][CrossRef]
138. Vetting MW,, Roderick SL,, Yu M,, Blanchard JS . 2003. Crystal structure of mycothiol synthase (Rv0819) from Mycobacterium tuberculosis shows structural homology to the GNAT family of N-acetyltransferases. Protein Sci 12 : 1954 1959.[PubMed][CrossRef]
139. Koledin T,, Newton GL,, Fahey RC . 2002. Identification of the mycothiol synthase gene ( mshD) encoding the acetyltransferase producing mycothiol in actinomycetes. Arch Microbiol 178 : 331 337.[PubMed][CrossRef]
140. Vetting MW,, Frantom PA,, Blanchard JS . 2008. Structural and enzymatic analysis of MshA from Corynebacterium glutamicum. J Biol Chem 283 : 15834 15844.[PubMed][CrossRef]
141. Vetting MW,, Yu M,, Rendle PM,, Blanchard JS . 2006. The substrate-induced conformational change of Mycobacterium tuberculosis mycothiol synthase. J Biol Chem 281 : 2795 2802.[PubMed][CrossRef]
142. Bone R,, Frank L,, Springer JP,, Pollack SJ,, Osborne S,, Atack JR,, Knowles MR,, McAllister G,, Ragan CI . 1994. Structural analysis of inositol monophosphatase complexes with substrates. Biochemistry 33 : 9460 9467.[PubMed][CrossRef]
143. Gu X,, Chen M,, Shen H,, Jiang X,, Huang Y,, Wang H . 2006. Rv2131c gene product: an unconventional enzyme that is both inositol monophosphatase and fructose-1,6-bisphosphatase. Biochem Biophys Res Commun 339 : 897 904.[PubMed][CrossRef]
144. Hatzios SK,, Iavarone AT,, Bertozzi CR . 2008. Rv2131c from Mycobacterium tuberculosis is a CysQ 3′-phosphoadenosine-5′-phosphatase. Biochemistry 47 : 5823 5831.[PubMed][CrossRef]
145. Morgan AJ,, Wang YK,, Roberts MF,, Miller SJ . 2004. Chemistry and biology of deoxy-myo-inositol phosphates: stereospecificity of substrate interactions within an archaeal and a bacterial IMPase. J Am Chem Soc 126 : 15370 15371.[PubMed][CrossRef]
146. Newton GL,, Fahey RC . 2008. Regulation of mycothiol metabolism by σR and the thiol redox sensor anti-sigma factor RsrA. Mol Microbiol 68 : 805 809.[PubMed][CrossRef]
147. Park J-H,, Roe J-H . 2008. Mycothiol regulates and is regulated by a thiol-specific antisigma factor RsrA and σR in Streptomyces coelicolor. Mol Microbiol 68 : 861 870.[PubMed][CrossRef]
148. Trivedi A,, Singh N,, Bhat SA,, Gupta P,, Kumar A . 2012. Redox biology of tuberculosis pathogenesis. Adv Microb Physiol 60 : 263 324.[PubMed][CrossRef]
149. Newton GL,, Unson MD,, Anderberg SJ,, Aguilera JA,, Oh NN,, delCardayre SB,, Av-Gay Y,, Fahey RC . 1999. Characterization of Mycobacterium smegmatis mutants defective in 1-d-myo-Inosityl-2-amino-2-deoxy-α-d-glucopyranoside and mycothiol biosynthesis. Biochem Biophys Res Commun 255 : 239 244.[PubMed][CrossRef]
150. Xu X,, Vilcheze C,, Av-Gay Y,, Gomez-Velasco A,, Jacobs WR Jr . 2011. Precise null deletion mutations of the mycothiol synthesis genes reveal their role in isoniazid and ethionamide resistance in Mycobacterium smegmatis. Antimicrob Agents Chemother 55 : 3133 3139.[PubMed][CrossRef]
151. Rawat M,, Kovacevic S,, Billman-Jacobe H,, Av-Gay Y . 2003. Inactivation of mshB, a key gene in the mycothiol biosynthesis pathway in Mycobacterium smegmatis. Microbiology 149 : 1341 1349.[PubMed][CrossRef]
152. Rawat M,, Newton GL,, Ko M,, Martinez GJ,, Fahey RC,, Av-Gay Y . 2002. Mycothiol-deficient Mycobacterium smegmatis mutants are hypersensitive to alkylating agents, free radicals, and antibiotics. Antimicrob Agents Chemother 46 : 3348 3355.[PubMed][CrossRef]
153. Newton GL,, Ta P,, Fahey RC . 2005. A mycothiol synthase mutant of Mycobacterium smegmatis produces novel thiols and has an altered thiol redox status. J Bacteriol 187 : 7309 7316.[PubMed][CrossRef]
154. Almeida Da Silva PE,, Palomino JC . 2011. Molecular basis and mechanisms of drug resistance in Mycobacterium tuberculosis: classical and new drugs. J Antimicrob Chemother 66 : 1417 1430.[PubMed][CrossRef]
155. Newton GL,, Buchmeier N,, Fahey RC . 2008. Biosynthesis and functions of mycothiol, the unique protective thiol of actinobacteria. Microbiol Mol Biol Rev 72 : 471 494.[PubMed][CrossRef]
156. Rawat M,, Johnson C,, Cadiz V,, Av-Gay Y . 2007. Comparative analysis of mutants in the mycothiol biosynthesis pathway in Mycobacterium smegmatis. Biochem Biophys Res Commun 363 : 71 76.[PubMed][CrossRef]
157. Buchmeier N,, Fahey RC . 2006. The mshA gene encoding the glycosyltransferase of mycothiol biosynthesis is essential in Mycobacterium tuberculosis Erdman. FEMS Microbiol Lett 264 : 74 79. [PubMed][CrossRef]
158. Vilchèze C,, Av-Gay Y,, Attarian R,, Zhen L,, Hazbón MH,, Colangeli R,, Chen B,, Weijun L,, Alland D,, Sacchettini JC,, Jacobs WR Jr . 2008. Mycothiol biosynthesis is essential for ethionamide susceptibility in Mycobacterium tuberculosis. Mol Microbiol 69 : 1316 1329.[PubMed][CrossRef]
159. Buchmeier NA,, Newton GL,, Koledin T,, Fahey RC . 2003. Association of mycothiol with protection of Mycobacterium tuberculosis from toxic oxidants and antibiotics. Mol Microbiol 47 : 1723 1732.[PubMed][CrossRef]
160. Sareen D,, Newton GL,, Fahey RC,, Buchmeier NA . 2003. Mycothiol is essential for growth of Mycobacterium tuberculosis Erdman. J Bacteriol 185 : 6736 6740.[PubMed][CrossRef]
161. Buchmeier NA,, Newton GL,, Fahey RC . 2006. A mycothiol synthase mutant of Mycobacterium tuberculosis has an altered thiol-disulfide content and limited tolerance to stress. J Bacteriol 188 : 6245 6252.[PubMed][CrossRef]
162. Rengarajan J,, Bloom BR,, Rubin EJ . 2005. Genome-wide requirements for Mycobacterium tuberculosis adaptation and survival in macrophages. Proc Natl Acad Sci USA 102 : 8327 8332.[PubMed][CrossRef]
163. Patel MP,, Blanchard JS . 1999. Expression, purification, and characterization of Mycobacterium tuberculosis mycothione reductase. Biochemistry 38 : 11827 11833.[PubMed][CrossRef]
164. Patel MP,, Blanchard JS . 2001. Mycobacterium tuberculosis mycothione reductase: pH dependence of the kinetic parameters and kinetic isotope effects. Biochemistry 40 : 5119 5126.[PubMed][CrossRef]
165. Hayward D,, Wiid I,, van Helden P . 2004. Differential expression of mycothiol pathway genes: are they affected by antituberculosis drugs? IUBMB Life 56 : 131 138.[PubMed][CrossRef]
166. Van Laer K,, Buts L,, Foloppe N,, Vertommen D,, Van Belle K,, Wahni K,, Roos G,, Nilsson L,, Mateos LM,, Rawat M,, van Nuland NAJ,, Messens J . 2012. Mycoredoxin-1 is one of the missing links in the oxidative stress defence mechanism of mycobacteria. Mol Microbiol 86 : 787 804.[PubMed][CrossRef]
167. Vogt RN,, Steenkamp DJ,, Zheng RJ,, Blanchard JS . 2003. The metabolism of nitrosothiols in the mycobacteria: identification and characterization of S-nitrosomycothiol reductase. Biochem J 375 : 657 665.[PubMed][CrossRef]
168. Miller CC,, Rawat M,, Johnson T,, Av-Gay Y . 2007. Innate protection of Mycobacterium smegmatis against the antimicrobial activity of nitric oxide is provided by mycothiol. Antimicrob Agents Chemother 51 : 3364 3366.[PubMed][CrossRef]
169. Newton GL,, Av-Gay Y,, Fahey RC . 2000. A novel mycothiol-dependent detoxification pathway in mycobacteria involving mycothiol S-conjugate amidase. Biochemistry 39 : 10739 10746.[PubMed][CrossRef]
170. Steffek M,, Newton GL,, Av-Gay Y,, Fahey RC . 2003. Characterization of Mycobacterium tuberculosis mycothiol S-conjugate amidase. Biochemistry 42 : 12067 12076.[PubMed][CrossRef]
171. Rawat M,, Uppal M,, Newton G,, Steffek M,, Fahey RC,, Av-Gay Y . 2004. Targeted mutagenesis of the Mycobacterium smegmatis mca gene, encoding a mycothiol-dependent detoxification protein. J Bacteriol 186 : 6050 6058.[PubMed][CrossRef]
172. Chi H-W,, Huang C-C,, Chin D-H . 2012. Thiols screened by the neocarzinostatin protein for preserving or detoxifying its bound enediyne antibiotic. Chemistry 18 : 6238 6249.[PubMed][CrossRef]
173. Nicholas GM,, Eckman LL,, Newton GL,, Fahey RC,, Ray S,, Bewley CA . 2003. Inhibition and kinetics of Mycobacterium tuberculosis and Mycobacterium smegmatis mycothiol-S-conjugate amidase by natural product inhibitors. Bioorg Med Chem 11 : 601 608.[PubMed][CrossRef]
174. Nicholas GM,, Eckman LL,, Ray S,, Hughes RO,, Pfefferkorn JA,, Barluenga S,, Nicolaou KC,, Bewley CA . 2002. Bromotyrosine-derived natural and synthetic products as inhibitors of mycothiol-S-conjugate amidase. Bioorg Med Chem Lett 12 : 2487 2490.[PubMed][CrossRef]
175. Fetterolf B,, Bewley CA . 2004. Synthesis of a bromotyrosine-derived natural product inhibitor of mycothiol-S-conjugate amidase. Bioorg Med Chem Lett 14 : 3785 3788.[PubMed][CrossRef]
176. Metaferia BB,, Ray S,, Smith JA,, Bewley CA . 2007. Design and synthesis of substrate-mimic inhibitors of mycothiol-S-conjugate amidase from Mycobacterium tuberculosis. Bioorg Med Chem Lett 17 : 444 447.[PubMed][CrossRef]
177. Bzymek KP,, Newton GL,, Ta P,, Fahey RC . 2007. Mycothiol import by Mycobacterium smegmatis and function as a resource for metabolic precursors and energy production. J Bacteriol 189 : 6796 6805.[PubMed][CrossRef]
178. Anderberg SJ,, Newton GL,, Fahey RC . 1998. Mycothiol biosynthesis and metabolism. Cellular levels of potential intermediates in the biosynthesis and degradation of mycothiol in Mycobacterium smegmatis. J Biol Chem 273 : 30391 30397.[PubMed][CrossRef]
179. Seebeck FP . 2010. In vitro reconstitution of mycobacterial ergothioneine biosynthesis. J Am Chem Soc 132 : 6632 6633.[PubMed][CrossRef]
180. Tanret C . 1909. Sur une base novelle retirée du seigle ergote, l'ergothioneine. Compt Rend 149 : 222 224.
181. Barger G,, Ewins AJ . 1911. The constitution of ergothioneine: a betaine related to histidine. J Chem Soc Trans 99 : 2336 2341.[CrossRef]
182. Pfeiffer C,, Bauer T,, Surek B,, Schomig E,, Grundemann D . 2011. Cyanobacteria produce high levels of ergothioneine. Food Chem 129 : 1766 1769.[CrossRef]
183. Genghof DS,, Vandamme O . 1964. Biosynthesis of ergothioneine and hercynine by mycobacteria. J Bacteriol 87 : 852 862.[PubMed]
184. Genghof DS,, Inamine E,, Kovalenko V,, Melville DB . 1956. Ergothioneine in microorganisms. J Biol Chem 223 : 9 17.[PubMed]
185. Melville DB, . 1959. Ergothioneine, p. 155 204. In Harris RH,, Marrian GF,, Thimann KV (ed), Vitamins & Hormones, vol. 17. Academic Press, New York.
186. Melville DB,, Eich S . 1956. The occurrence of ergothioneine in plant material. J Biol Chem 218 : 647 651.[PubMed]
187. Fahey RC . 2013. Glutathione analogs in prokaryotes. Biochim Biophys Acta 1830 : 3182 3198.[PubMed][CrossRef]
188. Misra HP . 1974. Generation of superoxide free radical during the autoxidation of thiols. J Biol Chem 249 : 2151 2155.[PubMed]
189. Hua Long L,, Halliwell B . 2001. Oxidation and generation of hydrogen peroxide by thiol compounds in commonly used cell culture media. Biochem Biophys Res Commun 286 : 991 994.[PubMed][CrossRef]
190. Mayumi T,, Kawano H,, Sakamoto Y,, Suehisa E,, Kawai Y,, Hama T . 1978. Studies on ergothioneine. V. Determination by high performance liquid chromatography and application to metabolic research. Chem Pharm Bull 26 : 3772 3778.[PubMed][CrossRef]
191. Heath H,, Toennies G . 1958. The preparation and properties of ergothioneine disulphide. Biochem J 68 : 204 210.[PubMed]
192. Seebeck FP . 2010. In vitro reconstitution of mycobacterial ergothioneine biosynthesis. J Am Chem Soc 132 : 6632 6633.[PubMed][CrossRef]
193. Grundemann D,, Harlfinger S,, Golz S,, Geerts A,, Lazar A,, Berkels R,, Jung N,, Rubbert A,, Schomig E . 2005. Discovery of the ergothioneine transporter. Proc Natl Acad Sci USA 102 : 5256 5261.[PubMed][CrossRef]
194. Hanlon DP . 1971. Interaction of ergothioneine with metal ions and metalloenzymes. J Med Chem 14 : 1084 1087.[PubMed][CrossRef]
195. Motohashi N,, Mori I,, Sugiura Y . 1976. Complexing of copper ion by ergothioneine. Chemical Pharm Bull 24 : 2364 2368.[PubMed][CrossRef]
196. Zhu BZ,, Mao L,, Fan RM,, Zhu JG,, Zhang YN,, Wang J,, Kalyanaraman B,, Frei B . 2011. Ergothioneine prevents copper-induced oxidative damage to DNA and protein by forming a redox-inactive ergothioneine-copper complex. Chem Res Toxicol 24 : 30 34.[PubMed][CrossRef]
197. Kawano H,, Higuchi F,, Mayumi T,, Hama T . 1982. Studies on ergothioneine. VII. Some effects on ergothioneine on glycolytic metabolism in red blood cells from rats. Chem Pharm Bull 30 : 2611 2613.[PubMed][CrossRef]
198. Laurenza I,, Colognato R,, Migliore L,, Del Prato S,, Benzi L . 2008. Modulation of palmitic acid-induced cell death by ergothioneine: evidence of an anti-inflammatory action. Biofactors 33 : 237 247.[PubMed][CrossRef]
199. Rahman I,, Gilmour PS,, Jimenez LA,, Biswas SK,, Antonicelli F,, Aruoma OI . 2003. Ergothioneine inhibits oxidative stress- and TNF-alpha-induced NF-kappa B activation and interleukin-8 release in alveolar epithelial cells. Biochem Biophys Res Commun 302 : 860 864.[PubMed][CrossRef]
200. Akanmu D,, Cecchini R,, Aruoma OI,, Halliwell B . 1991. The antioxidant action of ergothioneine. Arch Biochem Biophys 288 : 10 16.[PubMed][CrossRef]
201. Aruoma OI,, Spencer JP,, Mahmood N . 1999. Protection against oxidative damage and cell death by the natural antioxidant ergothioneine. Food Chem Toxicol 37 : 1043 1053.[PubMed][CrossRef]
202. Mitsuyama H,, May JM . 1999. Uptake and antioxidant effects of ergothioneine in human erythrocytes. Clin Sci (Lond) 97 : 407 411.[PubMed][CrossRef]
203. Reglinski J,, Smith WE,, Sturrock RD . 1988. Spin-echo 1H NMR detected response of ergothioneine to oxidative stress in the intact human erythrocyte. Magn Reson Med 6 : 217 223.[PubMed][CrossRef]
204. Hartman PE . 1990. Ergothioneine as antioxidant. Methods Enzymol 186 : 310 318.[CrossRef]
205. Ey J,, Schomig E,, Taubert D . 2007. Dietary sources and antioxidant effects of ergothioneine. J Agric Food Chem 55 : 6466 6474.[PubMed][CrossRef]
206. Paul BD,, Snyder SH . 2010. The unusual amino acid L-ergothioneine is a physiologic cytoprotectant. Cell Death Differ 17 : 1134 1140.[PubMed][CrossRef]
207. Bello MH,, Barrera-Perez V,, Morin D,, Epstein L . 2012. The Neurospora crassa mutant NcDeltaEgt-1 identifies an ergothioneine biosynthetic gene and demonstrates that ergothioneine enhances conidial survival and protects against peroxide toxicity during conidial germination. Fungal Genet Biol 49 : 160 172.[PubMed][CrossRef]
208. Ta P,, Buchmeier N,, Newton GL,, Rawat M,, Fahey RC . 2011. Organic hydroperoxide resistance protein and ergothioneine compensate for loss of mycothiol in Mycobacterium smegmatis mutants. J Bacteriol 193 : 1981 1990.[PubMed][CrossRef]
209. Fraser RS . 1951. Blood ergothioneine levels in disease. J Lab Clin Med 37 : 199 206.[PubMed]
210. Mahasirimongkol S,, Yanai H,, Nishida N,, Ridruechai C,, Matsushita I,, Ohashi J,, Summanapan S,, Yamada N,, Moolphate S,, Chuchotaworn C,, Chaiprasert A,, Manosuthi W,, Kantipong P,, Kanitwittaya S,, Sura T,, Khusmith S,, Tokunaga K,, Sawanpanyalert P,, Keicho N . 2009. Genome-wide SNP-based linkage analysis of tuberculosis in Thais. Genes Immun 10 : 77 83.[PubMed][CrossRef]
211. Ridruechai C,, Mahasirimongkol S,, Phromjai J,, Yanai H,, Nishida N,, Matsushita I,, Ohashi J,, Yamada N,, Moolphate S,, Summanapan S,, Chuchottaworn C,, Manosuthi W,, Kantipong P,, Kanitvittaya S,, Sawanpanyalert P,, Keicho N,, Khusmith S,, Tokunaga K . 2010. Association analysis of susceptibility candidate region on chromosome 5q31 for tuberculosis. Genes Immun 11 : 416 422.[PubMed][CrossRef]
212. Chen F,, Xia Q,, Ju LK . 2003. Aerobic denitrification of Pseudomonas aeruginosa monitored by online NAD(P)H fluorescence. Appl Environ Microbiol 69 : 6715 6722.[PubMed][CrossRef]
213. Newton GL,, Fahey RC . 2002. Mycothiol biochemistry. Arch Microbiol 178 : 388 394.[PubMed][CrossRef]
214. Hwang C,, Sinskey AJ,, Lodish HF . 1992. Oxidized redox state of glutathione in the endoplasmic reticulum. Science 257 : 1496 1502.[PubMed][CrossRef]
215. Austin CD,, Wen X,, Gazzard L,, Nelson C,, Scheller RH,, Scales SJ . 2005. Oxidizing potential of endosomes and lysosomes limits intracellular cleavage of disulfide-based antibody-drug conjugates. Proc Natl Acad Sci USA 102 : 17987 17992.[PubMed][CrossRef]