Generic placeholder image

Current Proteomics

Editor-in-Chief

ISSN (Print): 1570-1646
ISSN (Online): 1875-6247

Research Article

Analysis of Membrane Proteins of Streptomycin-Resistant Mycobacterium tuberculosis Isolates

Author(s): Rananjay Singh, Devesh Sharma, Divakar Sharma, Mahendra Kumar Gupta and Deepa Bisht*

Volume 19, Issue 5, 2022

Published on: 28 June, 2022

Page: [388 - 399] Pages: 12

DOI: 10.2174/1570164619666220428082752

Price: $65

Abstract

Background: Drug-resistant tuberculosis remains a health security threat and resistance to second-line drugs limits the options for treatment. Consequently, there is an utmost need for identifying and characterizing new biomarkers/drug targets of prime importance. Membrane proteins have an anticipated role in biological processes and could qualify as biomarkers/drug targets. Streptomycin (SM) is recommended as a second-line treatment regimen only when amikacin resistance has been confirmed. As extensively drug-resistant (XDR) isolates are frequently cross-resistant to second-line injectable drugs, an untapped potential for the continued use of SM has been suggested.

Objective: The study aimed to analyze the membrane proteins overexpressed in SM resistant isolates of Mycobacterium tuberculosis using proteomics approaches.

Methods: Membrane proteins were extracted employing sonication and ultracentrifugation. Twodimensional gel electrophoresis (2DGE) of membrane proteins was performed and identification of proteins was done by liquid chromatography-mass spectrometry (LCMS) and bioinformatics tools.

Results: On analyzing the two-dimensional (2D) gels, five protein spots were found overexpressed in the membrane of SM resistant isolates. Docking analysis revealed that SM might bind to the conserved domain of overexpressed proteins and Group-based prediction system-prokaryotic ubiquitinlike protein (GPS-PUP) predicted potential pupylation sites within them.

Conclusion: These proteins might be of diagnostic importance for detecting the cases early and for exploring effective control strategies against drug-resistant tuberculosis, particularly SM.

Keywords: Streptomycin, tuberculosis, membrane proteins, proteomics, two-dimensional gel electrophoresis, mass spectrometry.

Graphical Abstract

[1]
Raviglione, M.C. The TB epidemic from 1992 to 2002. Tuberculosis (Edinb.), 2003, 83(1-3), 4-14.
[http://dx.doi.org/10.1016/S1472-9792(02)00071-9] [PMID: 12758183]
[2]
World Health Organization. Global tuberculosis report 2020; Geneva, Switzerland 2020. Available from: https://apps.who.int/iris/bit-stream/handle/10665/336069/9789240013131-eng.pdf
[3]
Schatz, A.; Bugle, E.; Waksman, S.A. Streptomycin, a substance exhibiting antibiotic activity against gram-positive and gram-negative bacteria. Proc. Soc. Exp. Biol. Med., 1944, 55(1), 66-69.
[http://dx.doi.org/10.3181/00379727-55-14461]
[4]
World Health Organization. Consolidated guidelines on drugresistant tuberculosis treatment; Geneva, Switzerland 2019. Available from: https://apps.who.int/iris/bitstream/handle/10665/311389/ 9789241550529-eng.pdf?sequence=1&isAllowed=y
[5]
Cohen, K.A.; Stott, K.E.; Munsamy, V.; Manson, A.L.; Earl, A.M.; Pym, A.S. Evidence for expanding the role of streptomycin in the management of drug-resistant Mycobacterium tuberculosis. Antimicrob. Agents Chemother., 2020, 64(9), e00860-e20.
[http://dx.doi.org/10.1128/AAC.00860-20] [PMID: 32540971]
[6]
Bespyatykh, J.A.; Shitikov, E.A.; Ilina, E.N. Proteomics for the investigation of mycobacteria. Acta Nat. (Engl. Ed.), 2017, 9(1), 15-25.
[http://dx.doi.org/10.32607/20758251-2017-9-1-15-25] [PMID: 28461970]
[7]
Mann, M.; Kulak, N.A.; Nagaraj, N.; Cox, J. The coming age of complete, accurate, and ubiquitous proteomes. Mol. Cell, 2013, 49(4), 583-590.
[http://dx.doi.org/10.1016/j.molcel.2013.01.029] [PMID: 23438854]
[8]
Tebbe, A.; Klammer, M.; Sighart, S.; Schaab, C.; Daub, H. Systematic evaluation of label-free and super-SILAC quantification for proteo-me expression analysis. Rapid Commun. Mass Spectrom., 2015, 29(9), 795-801.
[http://dx.doi.org/10.1002/rcm.7160] [PMID: 26377007]
[9]
Sinha, S.; Arora, S.; Kosalai, K.; Namane, A.; Pym, A.S.; Cole, S.T. Proteome analysis of the plasma membrane of Mycobacterium tuber-culosis. Comp. Funct. Genomics, 2002, 3(6), 470-483.
[http://dx.doi.org/10.1002/cfg.211] [PMID: 18629250]
[10]
Singhal, N.; Sharma, P.; Kumar, M.; Joshi, B.; Bisht, D. Analysis of intracellular expressed proteins of Mycobacterium tuberculosis clinical isolates. Proteome Sci., 2012, 10(1), 14.
[http://dx.doi.org/10.1186/1477-5956-10-14] [PMID: 22375954]
[11]
Kumar, B.; Sharma, D.; Sharma, P.; Katoch, V.M.; Venkatesan, K.; Bisht, D. Proteomic analysis of Mycobacterium tuberculosis isolates resistant to kanamycin and amikacin. J. Proteomics, 2013, 94, 68-77.
[http://dx.doi.org/10.1016/j.jprot.2013.08.025] [PMID: 24036035]
[12]
Zhu, C.; Zhao, Y.; Huang, X.; Pang, Y.; Zhao, Y.; Zhuang, Y.; He, X. Quantitative proteomic analysis of streptomycin resistant and sensi-tive clinical isolates of Mycobacterium tuberculosis. Wei Sheng Wu Hsueh Pao, 2013, 53(2), 154-163.
[PMID: 23627108]
[13]
Sigler, K.; Höfer, M. Biotechnological aspects of membrane function. Crit. Rev. Biotechnol., 1997, 17(2), 69-86.
[http://dx.doi.org/10.3109/07388559709146607] [PMID: 9192471]
[14]
Hoffmann, C.; Leis, A.; Niederweis, M.; Plitzko, J.M.; Engelhardt, H. Disclosure of the mycobacterial outer membrane: Cryo-electron tomography and vitreous sections reveal the lipid bilayer structure. Proc. Natl. Acad. Sci. USA, 2008, 105(10), 3963-3967.
[http://dx.doi.org/10.1073/pnas.0709530105] [PMID: 18316738]
[15]
Sharma, D.; Kumar, B.; Lata, M.; Joshi, B.; Venkatesan, K.; Shukla, S.; Bisht, D. Comparative proteomic analysis of aminoglycosides resistant and susceptible Mycobacterium tuberculosis clinical isolates for exploring potential drug targets. PLoS One, 2015, 10(10), e0139414.
[http://dx.doi.org/10.1371/journal.pone.0139414] [PMID: 26436944]
[16]
Abrahams, K.A.; Besra, G.S. Mycobacterial cell wall biosynthesis: A multifaceted antibiotic target. Parasitology, 2018, 145(2), 116-133.
[http://dx.doi.org/10.1017/S0031182016002377] [PMID: 27976597]
[17]
Chen, H.; Nyantakyi, S.A.; Li, M.; Gopal, P.; Aziz, D.B.; Yang, T.; Moreira, W.; Gengenbacher, M.; Dick, T.; Go, M.L. The mycobacterial membrane: A novel target space for anti-tubercular drugs. Front. Microbiol., 2018, 9, 1627.
[http://dx.doi.org/10.3389/fmicb.2018.01627] [PMID: 30072978]
[18]
Sharma, P.; Kumar, B.; Gupta, Y.; Singhal, N.; Katoch, V.M.; Venkatesan, K.; Bisht, D. Proteomic analysis of streptomycin resistant and sensitive clinical isolates of Mycobacterium tuberculosis. Proteome Sci., 2010, 8, 59.
[http://dx.doi.org/10.1186/1477-5956-8-59] [PMID: 21083941]
[19]
Sharma, D.; Bisht, D. Secretory proteome analysis of streptomycin-resistant Mycobacterium tuberculosis clinical isolates. SLAS Discov. Adv. Life Sci., 2017, 22(10), 1229-1238.
[20]
Palomino, J-C.; Martin, A.; Camacho, M.; Guerra, H.; Swings, J.; Portaels, F. Resazurin microtiter assay plate: Simple and inexpensive method for detection of drug resistance in Mycobacterium tuberculosis. Antimicrob. Agents Chemother., 2002, 46(8), 2720-2722.
[http://dx.doi.org/10.1128/AAC.46.8.2720-2722.2002] [PMID: 12121966]
[21]
Jadaun, G.P.S.; Agarwal, C.; Sharma, H.; Ahmed, Z.; Upadhyay, P.; Faujdar, J.; Gupta, A.K.; Das, R.; Gupta, P.; Chauhan, D.S.; Sharma, V.D.; Katoch, V.M. Determination of ethambutol MICs for Mycobacterium tuberculosis and Mycobacterium avium isolates by resazurin microtitre assay. J. Antimicrob. Chemother., 2007, 60(1), 152-155.
[http://dx.doi.org/10.1093/jac/dkm117] [PMID: 17483147]
[22]
Brodie, A.F.; Kalra, V.K.; Lee, S.H.; Cohen, N.S. Properties of energy-transducing systems in different types of membrane preparations from Mycobacterium phlei-preparation, resolution, and reconstitution. Methods Enzymol., 1979, 55, 175-200.
[http://dx.doi.org/10.1016/0076-6879(79)55024-1] [PMID: 156832]
[23]
Bradford, M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem., 1976, 72, 248-254.
[http://dx.doi.org/10.1016/0003-2697(76)90527-3] [PMID: 942051]
[24]
Görg, A.; Obermaier, C.; Boguth, G.; Harder, A.; Scheibe, B.; Wildgruber, R.; Weiss, W. The current state of two-dimensional electropho-resis with immobilized pH gradients. Electrophoresis, 2000, 21(6), 1037-1053.
[http://dx.doi.org/10.1002/(SICI)1522-2683(20000401)21:6<1037:AID-ELPS1037>3.0.CO;2-V] [PMID: 10786879]
[25]
Laemmli, U.K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 1970, 227(5259), 680-685.
[http://dx.doi.org/10.1038/227680a0] [PMID: 5432063]
[26]
Shevchenko, A.; Wilm, M.; Vorm, O.; Mann, M. Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal. Chem., 1996, 68(5), 850-858.
[http://dx.doi.org/10.1021/ac950914h] [PMID: 8779443]
[27]
Andrusier, N.; Nussinov, R.; Wolfson, H.J. FireDock: Fast interaction refinement in molecular docking. Proteins, 2007, 69(1), 139-159.
[http://dx.doi.org/10.1002/prot.21495] [PMID: 17598144]
[28]
Mashiach, E.; Schneidman-Duhovny, D.; Andrusier, N.; Nussinov, R.; Wolfson, H.J. FireDock: A web server for fast interaction refine-ment in molecular docking. Nucleic Acids Res., 2008, 36(Web Server issue), W229-32.
[http://dx.doi.org/10.1093/nar/gkn186] [PMID: 18424796]
[29]
Liu, Z.; Ma, Q.; Cao, J.; Gao, X.; Ren, J.; Xue, Y. GPS-PUP: Computational prediction of pupylation sites in prokaryotic proteins. Mol. Biosyst., 2011, 7(10), 2737-2740.
[http://dx.doi.org/10.1039/c1mb05217a] [PMID: 21850344]
[30]
Barandun, J.; Delley, C.L.; Weber-Ban, E. The pupylation pathway and its role in mycobacteria. BMC Biol., 2012, 10, 95.
[http://dx.doi.org/10.1186/1741-7007-10-95] [PMID: 23198822]
[31]
Zhang, J.; Wang, K.; Zhang, J.; Liu, S.S.; Dai, L.; Zhang, J-Y. Using proteomic approach to identify tumor-associated proteins as bi-omarkers in human esophageal squamous cell carcinoma. J. Proteome Res., 2011, 10(6), 2863-2872.
[http://dx.doi.org/10.1021/pr200141c] [PMID: 21517111]
[32]
Zhang, L.; Wang, Q.; Wang, W.; Liu, Y.; Wang, J.; Yue, J.; Xu, Y.; Xu, W.; Cui, Z.; Zhang, X.; Wang, H. Identification of putative bi-omarkers for the serodiagnosis of drug-resistant Mycobacterium tuberculosis. Proteome Sci., 2012, 10, 12.
[http://dx.doi.org/10.1186/1477-5956-10-12] [PMID: 22364187]
[33]
Peng, Z.; Chen, L.; Zhang, H. Serum proteomic analysis of Mycobacterium tuberculosis antigens for discriminating active tuberculosis from latent infection. J. Int. Med. Res., 2020, 48(3), 300060520910042.
[http://dx.doi.org/10.1177/0300060520910042] [PMID: 32216499]
[34]
Provvedi, R.; Boldrin, F.; Falciani, F.; Palù, G.; Manganelli, R. Global transcriptional response to vancomycin in Mycobacterium tuberculo-sis. Microbiology, 2009, 155(Pt 4), 1093-1102.
[http://dx.doi.org/10.1099/mic.0.024802-0] [PMID: 19332811]
[35]
Armstrong, R.M.; Adams, K.L.; Zilisch, J.E.; Bretl, D.J.; Sato, H.; Anderson, D.M.; Zahrt, T.C. Rv2744c is a PspA ortholog that regulates lipid droplet homeostasis and nonreplicating persistence in Mycobacterium tuberculosis. J. Bacteriol., 2016, 198(11), 1645-1661.
[http://dx.doi.org/10.1128/JB.01001-15] [PMID: 27002134]
[36]
Tonini, L.; Sadet, B.; Stella, A.; Bouyssié, D.; Nigou, J.; Burlet-Schiltz, O.; Rivière, M. Potential plasticity of the mannoprotein repertoire associated to Mycobacterium tuberculosis virulence unveiled by mass spectrometry-based glycoproteomics. Molecules, 2020, 25(10), E2348.
[http://dx.doi.org/10.3390/molecules25102348] [PMID: 32443484]
[37]
Pandey, R.; Rodriguez, G.M. A ferritin mutant of Mycobacterium tuberculosis is highly susceptible to killing by antibiotics and is unable to establish a chronic infection in mice. Infect. Immun., 2012, 80(10), 3650-3659.
[http://dx.doi.org/10.1128/IAI.00229-12] [PMID: 22802345]
[38]
Sharma, D.; Bisht, D. Role of bacterioferritin & Ferritin in M. tuberculosis pathogenesis and drug resistance: A future perspective by in-teractomic approach. Front. Cell. Infect. Microbiol., 2017, 7, 240.
[http://dx.doi.org/10.3389/fcimb.2017.00240] [PMID: 28642844]
[39]
Kruh-Garcia, N.A.; Wolfe, L.M.; Chaisson, L.H.; Worodria, W.O.; Nahid, P.; Schorey, J.S.; Davis, J.L.; Dobos, K.M. Detection of Myco-bacterium tuberculosis peptides in the exosomes of patients with active and latent M. tuberculosis infection using MRM-MS. PLoS One, 2014, 9(7), e103811.
[http://dx.doi.org/10.1371/journal.pone.0103811] [PMID: 25080351]
[40]
Chande, A.G.; Siddiqui, Z.; Midha, M.K.; Sirohi, V.; Ravichandran, S.; Rao, K.V.S. Selective enrichment of mycobacterial proteins from infected host macrophages. Sci. Rep., 2015, 5, 13430.
[http://dx.doi.org/10.1038/srep13430] [PMID: 26303024]
[41]
He, X.; Jiang, H-W.; Chen, H.; Zhang, H-N.; Liu, Y.; Xu, Z-W.; Wu, F-L.; Guo, S-J.; Hou, J-L.; Yang, M-K.; Yan, W.; Deng, J-Y.; Bi, L-J.; Zhang, X-E.; Tao, S-C. Systematic Identification of Mycobacterium tuberculosis Effectors Reveals that BfrB Suppresses Innate Immunity. Mol. Cell. Proteomics, 2017, 16(12), 2243-2253.
[http://dx.doi.org/10.1074/mcp.RA117.000296] [PMID: 29018126]
[42]
Choi, S.; Choi, H-G.; Shin, K-W.; Back, Y.W.; Park, H-S.; Lee, J.H.; Kim, H-J. Mycobacterium tuberculosis Protein Rv3841 Activates Den-dritic Cells and Contributes to a T Helper 1 Immune Response. J. Immunol. Res., 2018, 2018, 3525302.
[http://dx.doi.org/10.1155/2018/3525302] [PMID: 29736404]
[43]
Pawełczyk, J.; Brzostek, A.; Minias, A.; Płociński, P.; Rumijowska-Galewicz, A.; Strapagiel, D.; Zakrzewska-Czerwińska, J.; Dziadek, J. Cholesterol-dependent transcriptome remodeling reveals new insight into the contribution of cholesterol to Mycobacterium tuberculosis pathogenesis. Sci. Rep., 2021, 11(1), 12396.
[http://dx.doi.org/10.1038/s41598-021-91812-0] [PMID: 34117327]
[44]
Geluk, A.; Lin, M.Y.; van Meijgaarden, K.E.; Leyten, E.M.S.; Franken, K.L.M.C.; Ottenhoff, T.H.M.; Klein, M.R. T-cell recognition of the HspX protein of Mycobacterium tuberculosis correlates with latent M. tuberculosis infection but not with M. bovis BCG vaccination. Infect. Immun., 2007, 75(6), 2914-2921.
[http://dx.doi.org/10.1128/IAI.01990-06] [PMID: 17387166]
[45]
Gautam, U.S.; Sikri, K.; Tyagi, J.S. The residue threonine 82 of DevR (DosR) is essential for DevR activation and function in Mycobacte-rium tuberculosis despite its atypical location. J. Bacteriol., 2011, 193(18), 4849-4858.
[http://dx.doi.org/10.1128/JB.05051-11] [PMID: 21764934]
[46]
Castro-Garza, J.; García-Jacobo, P.; Rivera-Morales, L.G.; Quinn, F.D.; Barber, J.; Karls, R.; Haas, D.; Helms, S.; Gupta, T.; Blumberg, H.; Tapia, J.; Luna-Cruz, I.; Rendon, A.; Vargas-Villarreal, J.; Vera-Cabrera, L.; Rodríguez-Padilla, C. Detection of anti-HspX antibodies and HspX protein in patient sera for the identification of recent latent infection by Mycobacterium tuberculosis. PLoS One, 2017, 12(8), e0181714.
[http://dx.doi.org/10.1371/journal.pone.0181714] [PMID: 28813434]
[47]
Rizvi, N.; Singh, A.; Yadav, M.; Hussain, S.R.; Siddiqui, S.; Kumar, V.; Ali, S.; Agarwal, A. Role of alpha-crystallin, early-secreted anti-genic target 6-kDa protein and culture filtrate protein 10 as novel diagnostic markers in osteoarticular tuberculosis. J. Orthop. Translat., 2016, 6, 18-26.
[http://dx.doi.org/10.1016/j.jot.2016.01.001] [PMID: 30035079]
[48]
Zvi, A.; Ariel, N.; Fulkerson, J.; Sadoff, J.C.; Shafferman, A. Whole genome identification of Mycobacterium tuberculosis vaccine candi-dates by comprehensive data mining and bioinformatic analyses. BMC Med. Genomics, 2008, 1, 18.
[http://dx.doi.org/10.1186/1755-8794-1-18] [PMID: 18505592]
[49]
Jee, B.; Singh, Y.; Yadav, R.; Lang, F. Small heat shock protein16.3 of Mycobacterium tuberculosis: After two decades of functional char-acterization. Cell. Physiol. Biochem., 2018, 49(1), 368-380.
[http://dx.doi.org/10.1159/000492887] [PMID: 30138912]
[50]
Alhusain, F. HspX-mediated survival pathways of pathogenic mycobacteria. Saudi Med. J., 2021, 42(7), 721-727.
[http://dx.doi.org/10.15537/smj.2021.42.7.20200582] [PMID: 34187915]
[51]
Lucarelli, A.P.; Buroni, S.; Pasca, M.R.; Rizzi, M.; Cavagnino, A.; Valentini, G.; Riccardi, G.; Chiarelli, L.R. Mycobacterium tuberculosis phosphoribosylpyrophosphate synthetase: Biochemical features of a crucial enzyme for mycobacterial cell wall biosynthesis. PLoS One, 2010, 5(11), e15494.
[http://dx.doi.org/10.1371/journal.pone.0015494] [PMID: 21085589]
[52]
Alderwick, L.J.; Lloyd, G.S.; Lloyd, A.J.; Lovering, A.L.; Eggeling, L.; Besra, G.S. Biochemical characterization of the Mycobacterium tuberculosis phosphoribosyl-1-pyrophosphate synthetase. Glycobiology, 2011, 21(4), 410-425.
[http://dx.doi.org/10.1093/glycob/cwq173] [PMID: 21045009]
[53]
Breda, A.; Martinelli, L.K.B.; Bizarro, C.V.; Rosado, L.A.; Borges, C.B.; Santos, D.S.; Basso, L.A. Wild-type phosphoribosylpyrophos-phate synthase (PRS) from Mycobacterium tuberculosis: A bacterial class II PRS? PLoS One, 2012, 7(6), e39245.
[http://dx.doi.org/10.1371/journal.pone.0039245] [PMID: 22745722]
[54]
Zhou, W.; Tsai, A.; Dattmore, D.A.; Stives, D.P.; Chitrakar, I.; D’alessandro, A.M.; Patil, S.; Hicks, K.A.; French, J.B. Crystal structure of E. coli PRPP synthetase. BMC Struct. Biol., 2019, 19(1), 1.
[http://dx.doi.org/10.1186/s12900-019-0100-4] [PMID: 30646888]
[55]
Ratcliffe, A.J. Inosine 5′-monophosphate dehydrogenase inhibitors for the treatment of autoimmune diseases. Curr. Opin. Drug Discov. Devel., 2006, 9(5), 595-605.
[PMID: 17002220]
[56]
Chen, L.; Pankiewicz, K.W. Recent development of IMP dehydrogenase inhibitors for the treatment of cancer. Curr. Opin. Drug Discov. Devel., 2007, 10(4), 403-412.
[PMID: 17659481]
[57]
Nair, V.; Shu, Q. Inosine monophosphate dehydrogenase as a probe in antiviral drug discovery. Antivir. Chem. Chemother., 2007, 18(5), 245-258.
[http://dx.doi.org/10.1177/095632020701800501] [PMID: 18046958]
[58]
Hedstrom, L.; Liechti, G.; Goldberg, J.B.; Gollapalli, D.R. The antibiotic potential of prokaryotic IMP dehydrogenase inhibitors. Curr. Med. Chem., 2011, 18(13), 1909-1918.
[http://dx.doi.org/10.2174/092986711795590129] [PMID: 21517780]
[59]
Shah, C.P.; Kharkar, P.S. Inosine 5′-monophosphate dehydrogenase inhibitors as antimicrobial agents: Recent progress and future per-spectives. Future Med. Chem., 2015, 7(11), 1415-1429.
[http://dx.doi.org/10.4155/fmc.15.72] [PMID: 26230881]
[60]
Singh, V.; Donini, S.; Pacitto, A.; Sala, C.; Hartkoorn, R.C.; Dhar, N.; Keri, G.; Ascher, D.B.; Mondésert, G.; Vocat, A.; Lupien, A.; Som-mer, R.; Vermet, H.; Lagrange, S.; Buechler, J.; Warner, D.F.; McKinney, J.D.; Pato, J.; Cole, S.T.; Blundell, T.L.; Rizzi, M.; Mizrahi, V. The inosine monophosphate dehydrogenase, GuaB2, is a vulnerable new bactericidal drug target for tuberculosis. ACS Infect. Dis., 2017, 3(1), 5-17.
[http://dx.doi.org/10.1021/acsinfecdis.6b00102] [PMID: 27726334]
[61]
Juvale, K.; Shaik, A.; Kirubakaran, S. Inhibitors of inosine 5′-monophosphate dehydrogenase as emerging new generation antimicrobial agents. MedChemComm, 2019, 10(8), 1290-1301.
[http://dx.doi.org/10.1039/C9MD00179D] [PMID: 31534651]
[62]
Darwin, K.H.; Ehrt, S.; Gutierrez-Ramos, J-C.; Weich, N.; Nathan, C.F. The proteasome of Mycobacterium tuberculosis is required for resistance to nitric oxide. Science, 2003, 302(5652), 1963-1966.
[http://dx.doi.org/10.1126/science.1091176] [PMID: 14671303]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy