Generic placeholder image

Current Drug Discovery Technologies

Editor-in-Chief

ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

Review Article

Potential Drug Targets in Mycobacterial Cell Wall: Non-Lipid Perspective

Author(s): Shrayanee Das, Saif Hameed and Zeeshan Fatima*

Volume 17, Issue 2, 2020

Page: [147 - 153] Pages: 7

DOI: 10.2174/1570163815666180605113609

Price: $65

Abstract

Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB), still remains a deadly disease worldwide. With prolonged usage of anti-TB drugs, the current therapeutic regimes are becoming ineffective, particularly due to emergence of drug resistance in MTB. Under such compelling circumstances, it is pertinent to look for new drug targets. The cell wall envelope of MTB is composed of unique lipids that are frequently targeted for anti-TB therapy. This is evident from the fact that most of the commonly used front line drugs (Isoniazid and Ethambutol) act on lipid machinery of MTB. Thus, despite the fact that much of the attention is towards understanding the MTB lipid biology, in search for identification of new drug targets, our knowledge of bacterial cell wall non-lipid components remains rudimentary and underappreciated. Better understanding of such components of mycobacterial cell structure will help in the identification of new drug targets that can be utilized on the persistent mycobacterium. This review at a common platform summarizes some of the non-lipid cell wall components in MTB that have potential to be exploited as future drug targets.

Keywords: Mycobacterium, cell wall, drug target, tuberculosis, HIV, ∝-D-glucan.

Graphical Abstract

[1]
Brennan PJ. Structure of mycobacteria: recent developments in defining cell wall carbohydrates and proteins. Rev Infect Dis 1989; 11(2)(Suppl. 2): S420-30.
[http://dx.doi.org/10.1093/clinids/11.Supplement_2.S420] [PMID: 2469120]
[2]
Hameed S, Pal R, Fatima Z. Iron acquisition mechanisms: promising target against mycobacterium tuberculosis. Open Microbiol J 2015; 9: 91-7.
[http://dx.doi.org/10.2174/1874285801509010091] [PMID: 26464608]
[3]
AlMatar M, AlMandeal H, Var I, Kayar B, Köksal F. New drugs for the treatment of Mycobacterium tuberculosis infection. Biomed Pharmacother 2017; 91: 546-58.
[http://dx.doi.org/10.1016/j.biopha.2017.04.105] [PMID: 28482292]
[4]
Tanwar J, Das S, Fatima Z, Hameed S. Multidrug resistance: an emerging crisis. Interdiscip Perspect Infect Dis 2014; 2014541340
[http://dx.doi.org/10.1155/2014/541340] [PMID: 25140175]
[5]
Pal R, Fatima Z, Hameed S. Efflux pumps in drug resistance of mycobacterium tuberculosis: A panoramic view. Int J Curr Microbiol Appl Sci 2014; 3(8): 528-46.
[6]
AlMatar M, Makky EA, Yakıcı G, Var I, Kayar B, Köksal F. Antimicrobial peptides as an alternative to anti-tuberculosis drugs. Pharmacol Res 2018; 128: 288-305.
[http://dx.doi.org/10.1016/j.phrs.2017.10.011] [PMID: 29079429]
[7]
Silhavy TJ, Kahne D, Walker S. The bacterial cell envelope. Cold Spring Harb Perspect Biol 2010; 2(5)a000414
[http://dx.doi.org/10.1101/cshperspect.a000414] [PMID: 20452953]
[8]
Work E. The mucopeptides of bacterial cell walls. A review. J Gen Microbiol 1961; 25: 169-89.
[http://dx.doi.org/10.1099/00221287-25-2-167] [PMID: 13786683]
[9]
Scheffers DJ, Pinho MG. Bacterial cell wall synthesis: new insights from localization studies. Microbiol Mol Biol Rev 2005; 69(4): 585-607.
[http://dx.doi.org/10.1128/MMBR.69.4.585-607.2005] [PMID: 16339737]
[10]
Pandey D, Sinha SK, Maurya VK. Identification of cell-wall specific protein of mycobacterium tuberculosis by visual comparison of 2-dimensional cytosolic, membrane and cell-wall fractions proteins gels of m. tuberculosis. Int J Pharm Bio Sci 2017; 8(2): (B)139-45.
[11]
Niederweis M, Danilchanka O, Huff J, Hoffmann C, Engelhardt H. Mycobacterial outer membranes: in search of proteins. Trends Microbiol 2010; 18(3): 109-16.
[http://dx.doi.org/10.1016/j.tim.2009.12.005] [PMID: 20060722]
[12]
Anderson RJ. The chemistry of the lipids of the tubercle bacillus. Physiol Rev 1932; 12: 166-89.
[http://dx.doi.org/10.1152/physrev.1932.12.2.166]
[13]
Kaur D, Guerin ME, Skovierová H, Brennan PJ, Jackson M. Chapter 2: Biogenesis of the cell wall and other glycoconjugates of Mycobacterium tuberculosis. Adv Appl Microbiol 2009; 69: 23-78.
[http://dx.doi.org/10.1016/S0065-2164(09)69002-X] [PMID: 19729090]
[14]
Sambou T, Dinadayala P, Stadthagen G, et al. Capsular glucan and intracellular glycogen of Mycobacterium tuberculosis: biosynthesis and impact on the persistence in mice. Mol Microbiol 2008; 70(3): 762-74.
[http://dx.doi.org/10.1111/j.1365-2958.2008.06445.x] [PMID: 18808383]
[15]
Koliwer-Brandl H, Syson K, van de Weerd R, et al. Metabolic Network for the Biosynthesis of Intra- and Extracellular α-Glucans Required for Virulence of Mycobacterium tuberculosis. PLoS Pathog 2016; 12(8)e1005768
[http://dx.doi.org/10.1371/journal.ppat.1005768] [PMID: 27513637]
[16]
Daffé M, Etienne G. The capsule of Mycobacterium tuberculosis and its implications for pathogenicity. Tuber Lung Dis 1999; 79(3): 153-69.
[http://dx.doi.org/10.1054/tuld.1998.0200] [PMID: 10656114]
[17]
Cywes C, Hoppe HC, Daffé M, Ehlers MR. Nonopsonic binding of Mycobacterium tuberculosis to complement receptor type 3 is mediated by capsular polysaccharides and is strain dependent. Infect Immun 1997; 65(10): 4258-66.
[http://dx.doi.org/10.1128/IAI.65.10.4258-4266.1997] [PMID: 9317035]
[18]
Dkhar HK, Gopalsamy A, Loharch S, et al. Discovery of Mycobacterium tuberculosis α-1,4-glucan branching enzyme (GlgB) inhibitors by structure- and ligand-based virtual screening. J Biol Chem 2015; 290(1): 76-89.
[http://dx.doi.org/10.1074/jbc.M114.589200] [PMID: 25384979]
[19]
Bushra E, Adem J. Mycobacterial metabolic pathways as drug targets: A Review. Adv Life Sci Tech 2016; 44: 49-61.
[20]
Harathi N, Pulaganti M, Anuradha CM, Kumar Chitta S. Inhibition of mycobacterium-RmlA by molecular modeling, dynamics simulation, and docking. Adv Bioinforma 2016; 20169841250
[http://dx.doi.org/10.1155/2016/9841250] [PMID: 26981117]
[21]
Driessen AJM, Nouwen N. Protein translocation across the bacterial cytoplasmic membrane. Annu Rev Biochem 2008; 77: 643-67.
[http://dx.doi.org/10.1146/annurev.biochem.77.061606.160747] [PMID: 18078384]
[22]
Pogliano JA, Beckwith J. SecD and SecF facilitate protein export in Escherichia coli. EMBO J 1994; 13(3): 554-61.
[http://dx.doi.org/10.1002/j.1460-2075.1994.tb06293.x] [PMID: 8313900]
[23]
Arkowitz RA, Wickner W. SecD and SecF are required for the proton electrochemical gradient stimulation of preprotein translocation. EMBO J 1994; 13(4): 954-63.
[http://dx.doi.org/10.1002/j.1460-2075.1994.tb06340.x] [PMID: 8112309]
[24]
Nouwen N, Piwowarek M, Berrelkamp G, Driessen AJM. The large first periplasmic loop of SecD and SecF plays an important role in SecDF functioning. J Bacteriol 2005; 187(16): 5857-60.
[http://dx.doi.org/10.1128/JB.187.16.5857-5860.2005] [PMID: 16077136]
[25]
Duong F, Wickner W. The SecDFyajC domain of preprotein translocase controls preprotein movement by regulating SecA membrane cycling. EMBO J 1997; 16(16): 4871-9.
[http://dx.doi.org/10.1093/emboj/16.16.4871] [PMID: 9305629]
[26]
Målen H, De Souza GA, Pathak S, Søfteland T, Wiker HG. Comparison of membrane proteins of Mycobacterium tuberculosis H37Rv and H37Ra strains. BMC Microbiol 2011; 11: 18.
[http://dx.doi.org/10.1186/1471-2180-11-18] [PMID: 21261938]
[27]
Raynaud C, Papavinasasundaram KG, Speight RA, et al. The functions of OmpATb, a pore-forming protein of Mycobacterium tuberculosis. Mol Microbiol 2002; 46(1): 191-201.
[http://dx.doi.org/10.1046/j.1365-2958.2002.03152.x] [PMID: 12366842]
[28]
Stahl C, Kubetzko S, Kaps I, Seeber S, Engelhardt H, Niederweis M. MspA provides the main hydrophilic pathway through the cell wall of Mycobacterium smegmatis. Mol Microbiol 2001; 40(2): 451-64.
[http://dx.doi.org/10.1046/j.1365-2958.2001.02394.x] [PMID: 11309127]
[29]
Engelhardt H, Heinz C, Niederweis M. A tetrameric porin limits the cell wall permeability of Mycobacterium smegmatis. J Biol Chem 2002; 277(40): 37567-72.
[http://dx.doi.org/10.1074/jbc.M206983200] [PMID: 12130659]
[30]
Mailaender C, Reiling N, Engelhardt H, Bossmann S, Ehlers S, Niederweis M. The MspA porin promotes growth and increases antibiotic susceptibility of both Mycobacterium bovis BCG and Mycobacterium tuberculosis. Microbiology 2004; 150(Pt 4): 853-64.
[http://dx.doi.org/10.1099/mic.0.26902-0] [PMID: 15073295]
[31]
Brennan PJ, Nikaido H. The envelope of mycobacteria. Annu Rev Biochem 1995; 64: 29-63.
[http://dx.doi.org/10.1146/annurev.bi.64.070195.000333] [PMID: 7574484]
[32]
Draper P. The outer parts of the mycobacterial envelope as permeability barriers. Front Biosci 1998; 3: D1253-61.
[http://dx.doi.org/10.2741/A360] [PMID: 9851911]
[33]
Jarlier V, Nikaido H. Mycobacterial cell wall: structure and role in natural resistance to antibiotics. FEMS Microbiol Lett 1994; 123(1-2): 11-8.
[http://dx.doi.org/10.1111/j.1574-6968.1994.tb07194.x] [PMID: 7988876]
[34]
Lambert PA. Cellular impermeability and uptake of biocides and antibiotics in Gram-positive bacteria and mycobacteria. J Appl Microbiol 2002; 92(Suppl.): 46S-54S.
[http://dx.doi.org/10.1046/j.1365-2672.92.5s1.7.x] [PMID: 12000612]
[35]
Jarlier V, Nikaido H. Permeability barrier to hydrophilic solutes in Mycobacterium chelonei. J Bacteriol 1990; 172(3): 1418-23.
[http://dx.doi.org/10.1128/JB.172.3.1418-1423.1990] [PMID: 2307653]
[36]
De Voss JJ, Rutter K, Schroeder BG, Su H, Zhu Y, Barry CE III. The salicylate-derived mycobactin siderophores of Mycobacterium tuberculosis are essential for growth in macrophages. Proc Natl Acad Sci USA 2000; 97(3): 1252-7.
[http://dx.doi.org/10.1073/pnas.97.3.1252] [PMID: 10655517]
[37]
Gobin J, Horwitz MA. Exochelins of Mycobacterium tuberculosis remove iron from human iron-binding proteins and donate iron to mycobactins in the M. tuberculosis cell wall. J Exp Med 1996; 183(4): 1527-32.
[http://dx.doi.org/10.1084/jem.183.4.1527] [PMID: 8666910]
[38]
Quadri LEN, Sello J, Keating TA, Weinreb PH, Walsh CT. Identification of a Mycobacterium tuberculosis gene cluster encoding the biosynthetic enzymes for assembly of the virulence-conferring siderophore mycobactin. Chem Biol 1998; 5(11): 631-45.
[http://dx.doi.org/10.1016/S1074-5521(98)90291-5] [PMID: 9831524]
[39]
Gold B, Rodriguez GM, Marras SAE, Pentecost M, Smith I. The Mycobacterium tuberculosis IdeR is a dual functional regulator that controls transcription of genes involved in iron acquisition, iron storage and survival in macrophages. Mol Microbiol 2001; 42(3): 851-65.
[http://dx.doi.org/10.1046/j.1365-2958.2001.02684.x] [PMID: 11722747]
[40]
Salimizand H, Jamehdar SA, Nik LB, Sadeghian H. Design of peptides interfering with iron-dependent regulator (IdeR) and evaluation of Mycobacterium tuberculosis growth inhibition. Iran J Basic Med Sci 2017; 20(6): 722-8.
[PMID: 28868128]
[41]
Sauton B. Sur la nutrition minerale du bacille tuberculeux. C R Hebd Seances Acad Sci 1912; 155: 860-1.
[http://dx.doi.org/10.1371/journal.pone.0032421]
[42]
Pal R, Hameed S, Fatima Z. Iron deprivation affects drug susceptibilities of mycobacteria targeting membrane integrity. J Pathogens 2015; 2015938523
[http://dx.doi.org/10.1155/2015/938523] [PMID: 26779346]
[43]
Pal R, Hameed S, Sharma S, Fatima Z. Influence of iron deprivation on virulence traits of mycobacteria. Braz J Infect Dis 2016; 20(6): 585-91.
[http://dx.doi.org/10.1016/j.bjid.2016.08.010] [PMID: 27755980]
[44]
Imlay JA, Chin SM, Linn S. Toxic DNA damage by hydrogen peroxide through the Fenton reaction in vivo and in vitro. Science 1988; 240(4852): 640-2.
[http://dx.doi.org/10.1126/science.2834821] [PMID: 2834821]
[45]
Hantke K. Iron and metal regulation in bacteria. Curr Opin Microbiol 2001; 4(2): 172-7.
[http://dx.doi.org/10.1016/S1369-5274(00)00184-3] [PMID: 11282473]
[46]
Rodriguez GM, Gold B, Gomez M, Dussurget O, Smith I. Identification and characterization of two divergently transcribed iron regulated genes in Mycobacterium tuberculosis. Tuber Lung Dis 1999; 79(5): 287-98.
[http://dx.doi.org/10.1054/tuld.1999.0219] [PMID: 10707257]
[47]
Dussurget O, Rodriguez M, Smith I. An ideR mutant of Mycobacterium smegmatis has derepressed siderophore production and an altered oxidative-stress response. Mol Microbiol 1996; 22(3): 535-44.
[http://dx.doi.org/10.1046/j.1365-2958.1996.1461511.x] [PMID: 8939436]
[48]
Fields PI, Swanson RV, Haidaris CG, Heffron F. Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. Proc Natl Acad Sci USA 1986; 83(14): 5189-93.
[http://dx.doi.org/10.1073/pnas.83.14.5189] [PMID: 3523484]
[49]
Garcia-del Portillo F, Foster JW, Maguire ME, Finlay BB. Characterization of the micro-environment of Salmonella typhimurium-containing vacuoles within MDCK epithelial cells. Mol Microbiol 1992; 6(22): 3289-97.
[http://dx.doi.org/10.1111/j.1365-2958.1992.tb02197.x] [PMID: 1484485]
[50]
Booth IR. Regulation of cytoplasmic pH in bacteria. Microbiol Rev 1985; 49(4): 359-78.
[http://dx.doi.org/10.1128/MMBR.49.4.359-378.1985] [PMID: 3912654]
[51]
Buchmeier N, Blanc-Potard A, Ehrt S, Piddington D, Riley L, Groisman EA. A parallel intraphagosomal survival strategy shared by mycobacterium tuberculosis and Salmonella enterica. Mol Microbiol 2000; 35(6): 1375-82.
[http://dx.doi.org/10.1046/j.1365-2958.2000.01797.x] [PMID: 10760138]
[52]
Moncrief MBC, Maguire ME. Magnesium and the role of MgtC in growth of Salmonella typhimurium. Infect Immun 1998; 66(8): 3802-9.
[http://dx.doi.org/10.1128/IAI.66.8.3802-3809.1998] [PMID: 9673265]
[53]
Meena LS, Rajni . Survival mechanisms of pathogenic Mycobacterium tuberculosis H37Rv. FEBS J 2010; 277(11): 2416-27.
[http://dx.doi.org/10.1111/j.1742-4658.2010.07666.x] [PMID: 20553485]
[54]
Berthet FX, Rauzier J, Lim EM, Philipp W, Gicquel B, Portnoï D. Characterization of the Mycobacterium tuberculosis erp gene encoding a potential cell surface protein with repetitive structures. Microbiology 1995; 141(Pt 9): 2123-30.
[http://dx.doi.org/10.1099/13500872-141-9-2123] [PMID: 7496523]
[55]
Lim EM, Rauzier J, Timm J, et al. Identification of mycobacterium tuberculosis DNA sequences encoding exported proteins by using phoA gene fusions. J Bacteriol 1995; 177(1): 59-65.
[http://dx.doi.org/10.1128/JB.177.1.59-65.1995] [PMID: 7798150]
[56]
Cherayil BJ, Young RAAA. A 28-kDa protein from Mycobacterium leprae is a target of the human antibody response in lepromatous leprosy. J Immunol 1988; 141(12): 4370-5.
[PMID: 3058804]
[57]
Berthet FX, Lagranderie M, Gounon P, et al. Attenuation of virulence by disruption of the Mycobacterium tuberculosis erp gene. Science 1998; 282(5389): 759-62.
[http://dx.doi.org/10.1126/science.282.5389.759] [PMID: 9784137]
[58]
Flesselles B, Anand NN, Remani J, Loosmore SM, Klein MH. Disruption of the mycobacterial cell entry gene of Mycobacterium bovis BCG results in a mutant that exhibits a reduced invasiveness for epithelial cells. FEMS Microbiol Lett 1999; 177(2): 237-42.
[http://dx.doi.org/10.1111/j.1574-6968.1999.tb13738.x] [PMID: 10474190]
[59]
Arruda S, Bomfim G, Knights R, Huima-Byron T, Riley LW. Cloning of an M. tuberculosis DNA fragment associated with entry and survival inside cells. Science 1993; 261(5127): 1454-7.
[http://dx.doi.org/10.1126/science.8367727] [PMID: 8367727]
[60]
Cole ST, Brosch R, Parkhill J, et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 1998; 393(6685): 537-44.
[http://dx.doi.org/10.1038/31159] [PMID: 9634230]
[61]
Chitale S, Ehrt S, Kawamura I, et al. Recombinant Mycobacterium tuberculosis protein associated with mammalian cell entry. Cell Microbiol 2001; 3(4): 247-54.
[http://dx.doi.org/10.1046/j.1462-5822.2001.00110.x] [PMID: 11298648]
[62]
Menozzi FD, Rouse JH, Alavi M, et al. Identification of a heparin-binding hemagglutinin present in mycobacteria. J Exp Med 1996; 184(3): 993-1001.
[http://dx.doi.org/10.1084/jem.184.3.993] [PMID: 9064359]
[63]
Reddy VM, Kumar B. Interaction of Mycobacterium avium complex with human respiratory epithelial cells. J Infect Dis 2000; 181(3): 1189-93.
[http://dx.doi.org/10.1086/315327] [PMID: 10720553]
[64]
Pethe K, Alonso S, Biet F, et al. The heparin-binding haemagglutinin of M. tuberculosis is required for extrapulmonary dissemination. Nature 2001; 412(6843): 190-4.
[http://dx.doi.org/10.1038/35084083] [PMID: 11449276]

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