An overview of tuberculosis chemotherapy – a literature review
Keywords:
Tuberculosis, multi drug resistant, extremely drug resistant, immune modulatorAbstract
Tuberculosis (TB) is a major global health threat. The emergence of human immunodeficiency virus (HIV) and also multi drug resistant (MDR) and extremely drug resistant (XDR)-TB poses a vital challenge to the control of the disease. For the last 50 years, no new anti-TB drug has been discovered. This literature review provides a brief discussion of existing drugs and emerging drug targets, and also of the advantages of incorporating modern drug delivery systems and immune modulators in order to improve the existing treatment regimen in terms of better efficacy, reduced drug administration frequency, shortened period of treatment and reduced drug related toxicity. The investigation for a new drug target is essential to continue the battle against MDR and XDR-TB. However, owing to the enormous cost and time involved in new drug development, improvement of the existing treatment regimen is seen to be a valid alternative.
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FERENCES
Goletti D, Weissman D, Jackson RW, Graham NM, Vlahov D, Klein RS, Munsiff SS, LOrtona L, Cauda R, Fauci AS. Effect of Mycobacterium tuberculosis on HIV replication. Role of immune activation. J Immunol, 1996; 157:1271-1278.
Mariani F, Goletti D, Ciaramella A, Martino A, Colizzi V, Fraziano M. Macrophage response to Mycobacterium tuberculosis during HIV infection relationships between macrophage activation and apoptosis. CurrMol Med. 2001; 1:209-216.
Strohmeier GR, Fenton JM. Roles of lipoarabinomannan in the pathogenesis of tuberculosis. Microbes Infect. 1999; 1:709-717.
WHO multi/extremely drug resistant TB report 2010 last accessed on 15 Apr, 2010: http://whqlibdoc.who.int/publications/2010/9789241599191_eng.pdf.
Burman WJ, Dalton CB, Cohn DL, Butler JRG, Reves RR. A cost-effectiveness analysis of directly observed therapy vs self-administered therapy for treatment of tuberculosis. Chest. 1997; 112:63-70.
Tupasi TE, Gupta R, Quelapio MI, Orillaza RB, Mira NR, Mangubat NV, Belen V, Arnisto N, Macalintal L, Arabit M,Lagahid JY, Espinal M, Floyd K. Feasibility and cost-effectiveness of treating multidrug resistant tuberculosis: a cohort study in the Philippines. Plos Med. 2006; 3(9): e352.
Gandhi NR, Moll A, Sturm AW, Pawinski R, Govender T, Lalloo U, Zeller K, Andrews J, Friedland G. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet. 2006; 368:1575-1580.
Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D,etal. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998; 393:537-544.
DiMasi JA, Hansen RW, Grabowski HG. The price of innovation: new estimates of drug development cost. J Health Econ. 2003; 22:151-186.
Mitchison D. Basic mechanism of chemotherapy. Chest. 1979; 76:771-781.
Zhang Y. The magic bullets and tuberculosis drug targets. Annu Rev PharmacolToxicol. 2005; 45:529-564.
Hooper DC, Wolfson JS. The fluoroquinolonones: pharmacology, clinical uses and toxicities in humans. Antimicro Agents Chemother. 1985; 28:716-721.
Alangaden GJ, Lerner SA. The clinical use of fluoroquinolones for the treatment of mycobacterial diseases. Clin Infect Dise. 1997; 25:1213-1221.
Centers for Disease Control and Prevention (CDC). Update: Fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis infection, and revisions in American Thoracic Society/CDC recommendations—United States, 2001. MMWR Morb Mortal Wkly Rep. 2001; 50:733-735.
Nuermberger EL, Yoshimatsu T, Tyagi S, O'Brien RJ, Vernon AN, Chaisson RE, Bishai WR, Grosset JH. Moxifloxacin-containing regimen greatly reduces time to culture conversion in murine tuberculosis. Am J RespirCrit Care Med. 2004; 169:421–426.
Grimaldo ER, Tupasi TE, Rivera AB, Quelapio MI, Cardano RC, Derilo JO, Belen VA. Increased resistance to ciprofloxacin and ofloxacin in multidrug-resistant Mycobacterium tuberculosis isolates from patients seen at a tertiary hospital in Philippines. Int J Tuberc Lung Dis. 2001; 5:546-550.
Brogden RN, Fitton A. Rifabutin. A review of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1994; 47:983-1009.
Centers for Disease Control and Prevention (CDC). Updated guidelines for the use of rifabutin or rifampin for the treatment and prevention of tuberculosis among HIV-infected patients taking protease inhibitors or nonnucleoside reverse transcriptase inhibitors. MMWR Morb Mortal Wkly Rep. 1999; 49:185-189.
Centers for Disease Control and Prevention (CDC). Prevention and treatment of tuberculosis among patients with human immunodeficiency virus: principles of therapy and revised recommendations. Centers for Disease Control and Prevention. MMWR Recomm Rep. 1998; 47:1-58.
Dietze R, Teixeira L, Rocha LM, Palaci M, Johnson JL, Wells C, Rose L, Eisenach K, Ellner JJ. Safety and bactericidal activity of rifalzil in patients with pulmonary tuberculosis. Antimicrob Agents Chemother. 2001; 45:1972-1976.
Moellering RC. Linezolid; the first oxazolidinone antimicrobial. Ann Intern Med. 2003; 138:135-142.
Bozdogan B, Appelbaum PC. Oxazolidinones: activity, mode of action, and mechanism of resistance. Int J Antimicrob Agents. 2004; 23:113-119.
Williams KN, Stover CK, Tasneen TZR, Tyagi S, Grosset JH, Nuermberger E. Promising anti-tuberculosis activity of the oxazolidinone PNU-100480 relative to linezolid in the murine model. Am J RespirCrit Care Med. 2009; 180:371-376.
Stover CK, Warrener P, VanDevanter DR, Sherman DR, Arain TM, Langhorne MH, Anderson SW, Towell JA, Yuan Y, McMurray DN, Kreiswirth BN, Barry CE, Baker WR. A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis. Nature. 2000; 405: 962-966.
Barry CE, Boshoff HI, Dowd CS. Prospects for clinical introduction of nitroimidazole antibiotics for the treatment of tuberculosis. Curr Pharm Des. 2004; 10:3239-3262.
Sun Z, Zhang Y. Antituberculosis activity of certain antifungal and antihelmintic drugs. Tuberc Lung Dis. 1999; 79:319–320.
Leys D, Mowat CG, McLean KJ, Richmond A, Chapman SK, Walkinshaw MD, Munro AW. Atomic structure of Mycobacterium tuberculosis CYP121 to 1.06 A reveals novel features of cytochrome P450. J Biol Chem. 2003; 278:5141–5147.
Diacon AH, Pym A, Grobusch M, Patientia R, Rustomjee R, Page-Shipp L, etal. The Diarylquinoline TMC207 for multidrug-resistant tuberculosis. N Engl J Med. 2009; 360:2397-2405.
Andries K, Verhasselt P, Guillemont J, et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science. 2005; 307:223-227.
Koul A, Dendouga N, Vergauwen K, Molenberghs B, Vranckx L, Willebrords R, Ristic Z, Lill H, Dorange I, Guillemont J, Bald D, Andries K. Diarylquinolines target subunit c of mycobacterial ATP synthase. Nat Chem Biol. 2007; 3:323-324.
Amaral L, Kristiansen JE. Phenothiazines: an alternative to conventional therapy for the initial management of suspected multidrug resistant tuberculosis. A call for studies. Int J Antimicrob Agents. 2000; 14:173-176.
Amaral L, Kristiansen JE, Viveiros M, Atouguia J. Activity of phenothiazines against antibiotic-resistant Mycobacterium tuberculosis: a review supporting further studies that may elucidate the potential use of thioridazine as anti-tuberculosis therapy. J AntimicrobChemother. 2001; 47:505-511.
Amaral L, Kristiansen JE, Abebe LS, Millett W. Inhibition of the respiration of multi-drug resistant clinical isolates of Mycobacterium tuberculosis by thioridazine: potential use for initial therapy of freshly diagnosed tuberculosis. J AntimicrobChemother. 1996; 38:1049-1053.
Bettencourt MV, Bosne-David S, Amaral L. Comparative in vitro activity of phenothiazines against multidrug-resistant Mycobacterium tuberculosis. Int J Antimicrob Agents. 2000; 16:69-71.
Crowle AJ, Douvas GS, May MH. Chlorpromazine: a drug potentially useful for treating ycobacterial infections. Chemotherapy. 1992; 38:410-419.
Giglione C, Pierre M, Meinnel T. Peptide deformylase as a target for new generation, broad spectrum antimicrobial agents. MolMicrobiol. 2000; 36:1197–1205.
Sharma A, Khuller GK, Sharma S. Peptide deformylase – a promising therapeutic target for tuberculosis and antibacterial drug discovery. Expert OpinTher Targets. 2009; 13:753-765.
Teo JW, Thayalan P, Beer D, Yap AS, Nanjundappa M, Ngew X, etal. Peptide deformylase inhibitors as potent antimycobacterial agents. Antimicrob Agents Chemother. 2006; 50:3665-3673.
Hasan S, Daugelat S, Rao PS, Schreiber M. Prioritizing genomic drug targets in pathogens: application to Mycobacterium tuberculosis. PLosComput Biol. 2006; 2:540-550.
Khasnobis S, Escuyer VE, Chatterjee D. Emerging therapeutic targets in tuberculosis: post- genomic era. Expert OpinTher Targets. 2002; 6:21-40.
Brennan PJ, Crick DC. The cell-wall core of Mycobacterium tuberculosis in the context of drug discovery. Curr Top Med Chem. 2007; 7:475-488.
Eoh H, Brennan PJ, Crick DC. The Mycobacterium tuberculosis MEP (2C-methyl-D-erythritol 4-phosphate) pathway as a new drug target. Tuberculosis. 2009; 89:1-11.
Wolucka BA, McNeil MR, de Hoffmann E, Chojnacki T, Brennan PJ. Recognition of the lipid intermediate for arabinogalactan/arabinomannan biosynthesis and its relation to the mode of action of ethambutol on mycobacteria. J Biol Chem. 1994; 269:23328–23335.
Mahapatra S, Yagi T, Belisle JT, Espinosa BJ, Hill PJ, McNeil MR, Brennan PJ, Crick DC. Mycobacterial lipid II is composed of a complex mixture of modified muramyl and peptide moieties linked to decaprenyl phosphate. J Bacteriol. 2005; 187:2747–2757.
Anderson RG, Hussey H, Baddiley J. The mechanism of wall synthesis in bacteria. The organization of enzymes and isoprenoid phosphates in the membrane. Biochem J. 1972; 127:11–25.
Mckinney JD, Honer ZU, Bentrup K, Munoz-Elias EJ. Persistance of mycobacterium tuberculosis in macrophages and mice requires the glyoxalate shunt enzyme isocitratelyase. Nature. 2000; 406:683-685.
Savi S, Warner DF, Kana BD, Mckinney JD, Mizrahi V, Dawes SS. Functional characterisation of a vitamin B12-depandent methylmalonyl pathway in mycobacterium tuberculosis: implications for propionate metabolism during growth on fatty acids. J Bacteriol. 2008, 190:3886-3895.
Ducati RG, Basso LA, Santos DS. Mycobacterial shikimate pathway enzymes as targets for drug design. Current Drug Targets. 2007; 8:423-435.
Pavelka MS Jr, Chen B, Kelley CL, Collins FM, Jacobs WR Jr. Vaccine efficacy of alysine auxotroph of Mycobacterium tuberculosis. Infect Immun. 2003; 71:4190-4192.
Smith DA, Parish T, Stoker NG, Bancroft GJ. Characterization of auxotroph mutants of Mycobacterium tuberculosis and their potential as vaccine candidates. Infect Immun. 2001; 69:1142-1150.
Ryndak M, Wang S, Smith I. PhoP, a key player in Mycobacterium tuberculosis virulence. Trends Microbiol. 2008; 16:528-534.
Frigui W, Bottai D, Majlessi L, Monot M, Josselin E, Brodin P, Garnier T, Gicquel B, Martin C, Leclerc C, Cole ST, Brosch R. Control of M.tuberculosis ESAT-6 secretion and specific T cell recognition by PhoP. PLoSPathog. 2008; 4:e33.
Primm TP, Anderson SJ, Mizrahi V, Avarbock D, Rubin H, Barry CE III. The stringent response of Mycobacterium tuberculosis is required for long-term survival. J Bacteriol. 2000; 182:4889-4898.
Monfeli RR, Beeson C. Targeting iron acquisition by Mycobacterium tuberculosis. Infect Disord Drug Targets. 2007; 7:213-220.
Weinberga ED, Miklossy J. Iron withholding: a defense against disease. J Alzheimers Dis. 2008; 13:451–463.
Ferreras JA, Ryu JS, Di Lello F, Tan DS, Quadri LE. Small-molecule inhibition of siderophore biosynthesis in Mycobacterium tuberculosis and Yersinia pestis. Nat Chem Biol. 2005; 1:29-32.
Munro SA, Lewin SA, Smith HJ, Engel ME, Fretheim A, Volmink J. Patient adherence to tuberculosis treatment: a systematic review of qualitative research. PLoS Med. 2007; 4:e238.
Pandey R, Khuller GK. Nanotechnology based drug delivery system(s) for the management of tuberculosis. Indian J Exp Biol. 2006; 44:357-366.
Pandey R, Ahmed Z, Sharma S, Khuller GK. Nanoparticle encapsulated antituberculosis drugs as a potential oral drug delivery system against murine tuberculosis. Tuberculosis (Edinb). 2003; 83: 373-378.
Sharma A, Pandey R, Sharma S, Khuller GK. Chemotherapeutic efficacy of poly (DL-lactide-co-glycolide) nanoparticle encapsulated antituberculosis drugs at sub-therapeutic dose against experimental tuberculosis. Int J Antimicrob Agent. 2004; 24:599-604.
Pandey R, Sharma A, Zahoor A, Sharma S, Khuller GK, Prasad B. Poly (DL-lactide-co-glycolide) nanoparticle based inhalable sustained drug delivery system for experimental tuberculosis. J AntimicrobChemother. 2003; 52:981-986.
Deol P, Khuller GK. Lung specific stealth liposomes; stability, biodistribution and toxicity of liposomal antituberculosis drugs in mice. BiochemBiophysActa. 1997: 1334:161-172.
Pandey R, Sharma S, Khuller GK. Liposome based antituberculosis drug therapy in a guinea pig model of tuberculosis. Int J Antimicrob Agents. 2004; 23:414-415.
Pandey R, Khuller GK. Chemotherapeutic potential of alginate chitosan microspheres as antitubercular drug carriers. J AntimicrobChemother. 2004; 53: 635-640.
Shegokar R, Al Shaal L, Mitri K. Present status of nanoparticle research for treatment of Tuberculosis. J Pharm Pharm Sci. 2011; 14: 100-116.
Canetti G. The Tubercle bacillus in the pulmonary lesion of man. New York: Springer.1955.
Briken V, Porcelli SA, Besra GS, Kremer L. Mycobacterial lipoarabonamannan and relatedlipoglycans: from biogenesis to modulation of the immune response. MolMicrobiol. 2004; 53:391-403.
Jozefowski S, Sobota A, Kwiatkowska K. How Mycobacterium tuberculosis subverts host immune responses. Bio Essays. 2008; 30:943-954.
Tomioka H. Adjunctive immunotherapy of mycobacterial infections. Current Pharm Design. 2004; 10:3297-3312.
Cooper AM, Magram J, Ferrante J, Orme IM. Interleukin 12 (IL-12) is crucial to the development of protective immunity in mice intravenously infected with Mycobacterium tuberculosis. J Exp Med. 1997; 186:39-45.
Altare F, Durandy A, Lammas D et.al. Impairment of mycobacterial immunity in human interleukin 12 receptor defiency. Science. 1998; 280:1432-1435.
Casanova JL. Mendelian susceptibility to mycobacterial infection in man. Swiss Med Wkly.2001, 131:445–454.
Ha SJ, Park SH, Kim HJ, Kim SC, Kang HJ, Lee EG, Kwon SG, Kim BM, Lee SH, Kim WB, SungYC, Cho SN. Enhanced immunogenicity and protective efficacy with the use of interleukin-12-encapsulated microspheres plus AS01B in tuberculosis subunit vaccination. Infect Immun. 2006; 74:4954-4959.
Doherty TM, Sher A. IL-12 promotes drug-induced clearance of Mycobacteriumavium infection in mice. J Immunol. 1998; 160:5428-5435.
Wang Z, Qiu SJ, Ye SL, Tang ZY and Xiao X. Combined IL-12 and GM-CSF gene therapy for murine hepatocellular carcinoma. Cancer Gene Ther. 2001; 8:751-758.
Douvas GS, Looker DL, Vatter AE, Crowel AJ. Interferon-γ activates human macrophages to become tumoricidal and leishmanicidal but enhances duplication of macrophage-associated mycobacteria. Infect Immunol. 1985; 50:1-8.
Rook GAW, Steele J, Ainsworth M, Champion BR. Activation of macrophages to inhibit proliferation of Mycobacterium tuberculosis: comparison of the effects of recombinant gamma interferon on human monocytes and murine peritoneal macrophage. Immunology. 1986; 59:333-338.
Condos R, Rom WN, Schluger NW. Treatment of multidrug-resistant pulmonary tuberculosis with interferon gamma via aerosol. Lancet. 1997; 349:1513-1515.
Squires KE, Brown ST, Armstrong D, Murphy WF, Murray HW. Interferon-gamma treatment for Mycobacterium aviumintracellulre complex bacillemia in patients with AIDS. J Infect Dis. 1992; 166:686-687.
Newport MJ, Awomoyi AA, Blackwell JM. Polymorphism in the interferon-gamma receptor-1 gene and susceptibility to pulmonary tuberculosis in the Gambia. Scand J Immunol. 2003; 58:383–385.
Cooke GS, Campbell SJ, Sillah J, Gustafson P, Bah B, Sirugo G, Bennett S, McAdam KP, Sow O, Lienhardt C, Hill AV. Polymorphism within the interferon-gamma/receptor complex is associated with pulmonary tuberculosis. Am J RespirCrit Care Med. 2006; 174:339–343.
Stein CM, Zalwango S, Chiunda AB, Millard C, Leontiev DV, Horvath AL, Cartier KC, Chervenak K, Boom WH, Elston RC, Mugerwa RD, Whalen CC, Iyengar SK. Linkage and association analysis of candidate genes for TB and TNF alpha cytokine expression: evidence for association with IFNGR1, IL-10, and TNF receptor 1 genes. Hum Genet. 2007; 121:663-673.
Ding AH, Nathan CF, Stuehr DJ. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immunol. 1988; 141:2407–2412.
Flesch IE, Hess JH, Oswald IP, Kaufmann SH. Growth inhibition of Mycobacterium bovis by IFN-gamma stimulated macrophages: regulation by endogenous tumour necrosis factor-alpha and by IL-10. IntImmunol. 1994; 6:693–700.
Bean AG, Roach DR, Briscoe H, FranceMP, Korner H, Sedgwick JD, Britton WJ. Structural deficiencies in granuloma formation in TNF gene-targeted mice underlie the heightened susceptibility to aerosol Mycobacterium tuberculosis infection, which is not compensated for by lymphotoxin. J Immunol. 1999; 162:3504–3511.
Flynn JL, Goldstein MM, Chan J, Triebold KJ, Pfeffer K, Lowenstein CJ, Schreiber R, Mak TW, Bloom BR. Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice. Immunity. 1995; 2:561–572.
Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD, Siegel JN, Braun MM. Tuberculosis associated with infliximab, a tumour necrosis factor alphaneutralizing agent. N Engl J Med. 2001; 345:1098–1104.
Hickman SP, Chan J, Salgame P. Mycobacterium tuberculosis induces differential cytokine roduction from dendritic cells and macrophages with divergent effect on naive T cell polarization. J Immunol. 2002; 168:4636-4642.
Silva RA, Pais TF, Appelberg R. Blocking the receptor for IL-10 improves antimycobacterial chemotherapy and vaccination. J Immunol. 2001; 167:1535-1541.
Rigopoulou EI, Abbot WGH, Haigh P, Naoumov NV. Blocking the interleukin-10 receptor- a novel approach to stimulate T-helper cell type 1 responses to hepatitis C virus. ClinImmunol. 2005; 117:57-64.
Selvaraj P, Chandra G, Jawahar MS, Rani MV, Rajeshwari DN, Narayanan PR. Regulatory role of vitamin D receptor gene variants of Bsm I, Apa I, Taq I, and Fok I polymorphisms on macrophage phagocytosis and lymphoproliferative response to Mycobacterium tuberculosis antigen in pulmonary tuberculosis. J ClinImmunol. 2004; 24:523–532.
Chocano-Bedoya P, Ronnenberg AG. Vitamin D and tuberculosis. Nutr Rev. 2009; 67:289-293.
Martineau AR, Honecker FU, Wilkinson RJ, Griffiths CJ. Vitamin D in the treatment of pulmonary tuberculosis. J Steroid BiochemMol Biol. 2007; 103:793–798.
Liu PT. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006; 311:1770–1773.
Harvard gazette archives (last accessed on 25 Apr, 2010): http://www.news.harvard.edu/gazette/2006/03.09/01-tb.html.
Peterson JD, Herzenberg LA, Vasquez K,Waltenbaugh C. Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns. Proc Nat AcadSci USA. 1998; 95:3071-3076.
Venketaraman V, Millman A, Salman M, Swaminathan S, Goetz M, Lardizabal A, David Hom, Connell ND. Glutathione levels and immune responses in tuberculosis patients. MicrobPathog. 2008; 44:255-261.
Connell ND, Venketaraman V. Control of Mycobacterium tuberculosis infection by glutathione. Recent Pat Antiinfect Drug Discov. 2009; 4:214-226.
Venketaraman V, Dayaram YK, Talaue MT, Connell ND. Glutathione and nitrosoglutathione in macrophage defense against M. Tuberculosis. Infect Immunity. 2005; 73:1886-1894.
Venketaraman V, Rodgers T, Linares R, Reilly N, Swaminathan S, Hom D, Millman AC, Wallis R, Connell ND. Glutathione and growth inhibition of Mycobacterium tuberculosis in healthy and HIV infected subjects. AIDS Res Therap. 2006; 3:5.
Barrow WW. Microsphere technology for chemotherapy of mycobacterial infections. Curr Pharm Des. 2004; 10:3275-3284.
Barrow ELW, Winchester GA, Staas JK, Quenelle DC, Barrow WW. Use of microsphere technology for sustained and targeted delivery of rifampin to Mycobacterium tuberculosis- infected macrophages. Antimicrob Agents Chemother. 1998; 42:2682-2689.
Schlesinger LS. Macrophage phagocytosis of virulent but not attenuated strains of Mycobacterium tuberculosis is mediated by mannose receptors in addition to complement receptors. J Immunol. 1993; 150:2920-2930.
Taylor ML, Noble PW, White B, Wise R, Liu MC and Bochner BS. Extensive surface phenotyping of alveolar macrophages in interstitial lung disease. ClinImmunol. 2000; 94:33-41.
Akasaka Y, Ueda H, Takayama K, Machida Y, Nagai T. Preparation and evaluation of bovine serumalbumin nanospheres coated with monoclonal antibodies. Drug Des Deliv. 1988; 3:85-97.
Dye C. Global epidemiology of tuberculosis. Lancet. 2006; 367:938–940.
Schneemann M, Schoedon G, Hofer S, Blau N, Guerrero L, Schaffner A. Nitric oxide synthase is not a constituent of the antimicrobial armature of human mononuclear phagocytes. J Infect Dis. 1993; 167:1358–1363.
MacMicking J, Xie Q, Nathan C. Nitric oxide andmacrophage function. Ann Rev Immunol.1997; 15:323–350.
Kalia VC, Rani A, Lal S, Cheema S, Raut CP. Combing databases reveals potential antibiotic producers. ExpOpin Drug Disc. 2007; 2:211-224.
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