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ISSN (Print): 2212-7968
ISSN (Online): 1872-3136

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Review Article

Exploration of Ion Channels in Mycobacterium tuberculosis: Implication on Drug Discovery and Potent Drug Targets Against Tuberculosis

Author(s): Manish Dwivedi*

Volume 14, Issue 1, 2020

Page: [14 - 29] Pages: 16

DOI: 10.2174/2212796814666200310100746

Price: $65

Abstract

Scientific interest in mycobacteria has been sparked by the medical importance of Mycobacterium tuberculosis (Mtb) that is known to cause severe diseases in mammals, i.e. tuberculosis and by properties that distinguish them from other microorganisms which are notoriously difficult to treat. The treatment of their infections is difficult because mycobacteria fortify themselves with a thick impermeable cell envelope. Channel and transporter proteins are among the crucial adaptations of Mycobacterium that facilitate their strength to combat against host immune system and anti-tuberculosis drugs. In previous studies, it was investigated that some of the channel proteins contribute to the overall antibiotic resistance in Mtb. Moreover, in some of the cases, membrane proteins were found responsible for virulence of these pathogens. Given the ability of M. tuberculosis to survive as an intracellular pathogen and its inclination to develop resistance to the prevailing anti-tuberculosis drugs, its treatment requires new approaches and optimization of anti-TB drugs and investigation of new targets are needed for their potential in clinical usage. Therefore, it is imperative to investigate the survival of Mtb. in stressed conditions with different behavior of particular channel/ transporter proteins. Comprehensive understanding of channel proteins and their mechanism will provide us direction to find out preventive measures against the emergence of resistance and reduce the duration of the treatment, eventually leading to plausible eradication of tuberculosis.

Keywords: Ion channels, Mycobacterium, drug discovery, tuberculosis, membrane proteins, potent drug targets.

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[1]
Hoagland DT, Liu J, Lee RB, Lee RE. New agents for the treatment of drug-resistant Mycobacterium tuberculosis. Adv Drug Deliv Rev 2016; 102: 55-72.
[http://dx.doi.org/10.1016/j.addr.2016.04.026] [PMID: 27151308]
[2]
Chen H, Nyantakyi SA, Li M, et al. 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]
[3]
Li H, Liu L, Zhang WJ, et al. Analysis of the antigenic properties of membrane proteins of Mycobacterium tuberculosis. Sci Rep 2019; 9(1): 3042.
[http://dx.doi.org/10.1038/s41598-019-39402-z] [PMID: 30816178]
[4]
Liu L, Zhang WJ, Zheng J, et al. Exploration of novel cellular and serological antigen biomarkers in the ORFeome of Mycobacterium tuberculosis. Mol Cell Proteomics 2014; 13(3): 897-906.
[http://dx.doi.org/10.1074/mcp.M113.032623] [PMID: 24447912]
[5]
Wells RM, Jones CM, Xi Z, et al. Discovery of a siderophore export system essential for virulence of Mycobacterium tuberculosis. PLoS Pathog 2013; 9(1)e1003120
[http://dx.doi.org/10.1371/journal.ppat.1003120] [PMID: 23431276]
[6]
Musser JM. Antimicrobial agent resistance in mycobacteria: molecular genetic insights. Clin Microbiol Rev 1995; 8(4): 496-514.
[http://dx.doi.org/10.1128/CMR.8.4.496] [PMID: 8665467]
[7]
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]
[8]
Tekaia F, Gordon SV, Garnier T, Brosch R, Barrell BG, Cole ST. Analysis of the proteome of Mycobacterium tuberculosis in silico. Tuber Lung Dis 1999; 79(6): 329-42.
[http://dx.doi.org/10.1054/tuld.1999.0220] [PMID: 10694977]
[9]
Machado D, Pires D, Perdigão J, et al. Ion channel blockers as antimicrobial agents, efflux inhibitors, and enhancers of macrophage killing activity against drug resistant Mycobacterium tuberculosis. PLoS One 2016; 11(2): e0149326
[http://dx.doi.org/10.1371/journal.pone.0149326] [PMID: 26919135]
[10]
Gupta S, Tyagi S, Almeida DV, Maiga MC, Ammerman NC, Bishai WR. Acceleration of tuberculosis treatment by adjunctive therapy with verapamil as an efflux inhibitor. Am J Respir Crit Care Med 2013; 188(5): 600-7.
[http://dx.doi.org/10.1164/rccm.201304-0650OC] [PMID: 23805786]
[11]
Louw GE, Warren RM, Gey van Pittius NC, et al. Rifampicin reduces susceptibility to ofloxacin in rifampicin-resistant Mycobacterium tuberculosis through efflux. Am J Respir Crit Care Med 2011; 184(2): 269-76.
[http://dx.doi.org/10.1164/rccm.201011-1924OC] [PMID: 21512166]
[12]
Ordway D, Viveiros M, Leandro C, et al. Clinical concentrations of thioridazine kill intracellular multidrug-resistant Mycobacterium tuberculosis. Antimicrob Agents Chemother 2003; 47(3): 917-22.
[http://dx.doi.org/10.1128/AAC.47.3.917-922.2003] [PMID: 12604522]
[13]
Pasca MR, Guglierame P, De Rossi E, Zara F, Riccardi G. mmpL7 gene of Mycobacterium tuberculosis is responsible for isoniazid efflux in Mycobacterium smegmatis. Antimicrob Agents Chemother 2005; 49(11): 4775-7.
[http://dx.doi.org/10.1128/AAC.49.11.4775-4777.2005] [PMID: 16251328]
[14]
Sackin H. Mechanosensitive channels. Annu Rev Physiol 1995; 57: 333-53.
[http://dx.doi.org/10.1146/annurev.ph.57.030195.002001] [PMID: 7539988]
[15]
Sukharev SI, Blount P, Martinac B, Blattner FR, Kung C. A large-conductance mechanosensitive channel in E. coli encoded by mscL alone. Nature 1994; 368(6468): 265-8.
[http://dx.doi.org/10.1038/368265a0] [PMID: 7511799]
[16]
Moe PC, Blount P, Kung C. Functional and structural conservation in the mechanosensitive channel MscL implicates elements crucial for mechanosensation. Mol Microbiol 1998; 28(3): 583-92.
[http://dx.doi.org/10.1046/j.1365-2958.1998.00821.x] [PMID: 9632260]
[17]
Sukharev SI, Blount P, Martinac B, Kung C. Mechanosensitive channels of Escherichia coli: the MscL gene, protein, and activities. Annu Rev Physiol 1997; 59: 633-57.
[http://dx.doi.org/10.1146/annurev.physiol.59.1.633] [PMID: 9074781]
[18]
Chang G, Spencer RH, Lee AT, Barclay MT, Rees DC. Structure of the MscL homolog from Mycobacterium tuberculosis: a gated mechanosensitive ion channel. Science 1998; 282(5397): 2220-6.
[http://dx.doi.org/10.1126/science.282.5397.2220] [PMID: 9856938]
[19]
Martinac B, Adler J, Kung C. Mechanosensitive ion channels of E. coli activated by amphipaths. Nature 1990; 348(6298): 261-3.
[http://dx.doi.org/10.1038/348261a0] [PMID: 1700306]
[20]
Aínsa JA, Blokpoel MC, Otal I, Young DB, De Smet KA, Martín C. Molecular cloning and characterization of Tap, a putative multidrug efflux pump present in Mycobacterium fortuitum and Mycobacterium tuberculosis. J Bacteriol 1998; 180(22): 5836-43.
[http://dx.doi.org/10.1128/JB.180.22.5836-5843.1998] [PMID: 9811639]
[21]
Griffith JK, Baker ME, Rouch DA, et al. Membrane transport proteins: implications of sequence comparisons. Curr Opin Cell Biol 1992; 4(4): 684-95.
[http://dx.doi.org/10.1016/0955-0674(92)90090-Y] [PMID: 1419050]
[22]
Marger MD, Saier MH Jr. A major superfamily of transmembrane facilitators that catalyse uniport, symport and antiport. Trends Biochem Sci 1993; 18(1): 13-20.
[http://dx.doi.org/10.1016/0968-0004(93)90081-W] [PMID: 8438231]
[23]
Doran JL, Pang Y, Mdluli KE, et al. Mycobacterium tuberculosis efpA encodes an efflux protein of the QacA transporter family. Clin Diagn Lab Immunol 1997; 4(1): 23-32.
[http://dx.doi.org/10.1128/CDLI.4.1.23-32.1997] [PMID: 9008277]
[24]
Niederweis M, Ehrt S, Heinz C, et al. Cloning of the mspA gene encoding a porin from Mycobacterium smegmatis. Mol Microbiol 1999; 33(5): 933-45.
[http://dx.doi.org/10.1046/j.1365-2958.1999.01472.x] [PMID: 10476028]
[25]
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: : 451-64. Authors’ correction appeared in Mol Microbiol 2001; 57: 1509..
[26]
Stephan J, Bender J, Wolschendorf F, et al. The growth rate of Mycobacterium smegmatis depends on sufficient porin-mediated influx of nutrients. Mol Microbiol 2005; 58(3): 714-30.
[http://dx.doi.org/10.1111/j.1365-2958.2005.04878.x] [PMID: 16238622]
[27]
Faller M, Niederweis M, Schulz GE. The structure of a mycobacterial outer-membrane channel. Science 2004; 303(5661): 1189-92.
[http://dx.doi.org/10.1126/science.1094114] [PMID: 14976314]
[28]
Senaratne RH, Mobasheri H, Papavinasasundaram KG, Jenner P, Lea EJ, Draper P. Expression of a gene for a porin-like protein of the OmpA family from Mycobacterium tuberculosis H37Rv. J Bacteriol 1998; 180(14): 3541-7.
[http://dx.doi.org/10.1128/JB.180.14.3541-3547.1998] [PMID: 9657995]
[29]
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]
[30]
Molle V, Saint N, Campagna S, et al. pH-dependent pore-forming activity of OmpATb from Mycobacterium tuberculosis and characterization of the channel by peptidic dissection. Mol Microbiol 2006; 61(3): 826-37.
[http://dx.doi.org/10.1111/j.1365-2958.2006.05277.x] [PMID: 16803587]
[31]
Alahari A, Saint N, Campagna S, Molle V, Molle G, Kremer L. The N-terminal domain of OmpATb is required for membrane translocation and pore-forming activity in mycobacteria. J Bacteriol 2007; 189(17): 6351-8.
[http://dx.doi.org/10.1128/JB.00509-07] [PMID: 17573469]
[32]
Siroy A, Mailaender C, Harder D, et al. Rv1698 of Mycobacterium tuberculosis represents a new class of channel-forming outer membrane proteins. J Biol Chem 2008; 283(26): 17827-37.
[http://dx.doi.org/10.1074/jbc.M800866200] [PMID: 18434314]
[33]
Wolschendorf F, Ackart D, Shrestha TB, et al. Copper resistance is essential for virulence of Mycobacterium tuberculosis. Proc Natl Acad Sci USA 2011; 108(4): 1621-6.
[http://dx.doi.org/10.1073/pnas.1009261108] [PMID: 21205886]
[34]
Danilchanka O, Sun J, Pavlenok M, et al. An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity. Proc Natl Acad Sci USA 2014; 111(18): 6750-5.
[http://dx.doi.org/10.1073/pnas.1400136111] [PMID: 24753609]
[35]
Danilchanka O, Pires D, Anes E, Niederweis M. The Mycobacterium tuberculosis outer membrane channel protein CpnT confers susceptibility to toxic molecules. Antimicrob Agents Chemother 2015; 59(4): 2328-36.
[http://dx.doi.org/10.1128/AAC.04222-14] [PMID: 25645841]
[36]
Leyton DL, Rossiter AE, Henderson IR. From self sufficiency to dependence: mechanisms and factors important for autotransporter biogenesis. Nat Rev Microbiol 2012; 10(3): 213-25.
[http://dx.doi.org/10.1038/nrmicro2733] [PMID: 22337167]
[37]
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]
[38]
Choudhuri BS, Bhakta S, Barik R, Basu J, Kundu M, Chakrabarti P. Overexpression and functional characterization of an ABC (ATP-binding cassette) transporter encoded by the genes drrA and drrB of Mycobacterium tuberculosis. Biochem J 2002; 367(Pt 1): 279-85.
[http://dx.doi.org/10.1042/bj20020615] [PMID: 12057006]
[39]
Molle V, Soulat D, Jault JM, Grangeasse C, Cozzone AJ, Prost JF. Two FHA domains on an ABC transporter, Rv1747, mediate its phosphorylation by PknF, a Ser/Thr protein kinase from Mycobacterium tuberculosis. FEMS Microbiol Lett 2004; 234(2): 215-23.
[http://dx.doi.org/10.1111/j.1574-6968.2004.tb09536.x] [PMID: 15135525]
[40]
Pasca MR, Guglierame P, Arcesi F, Bellinzoni M, De Rossi E, Riccardi G. Rv2686c-Rv2687c-Rv2688c, an ABC fluoroquinolone efflux pump in Mycobacterium tuberculosis. Antimicrob Agents Chemother 2004; 48(8): 3175-8.
[http://dx.doi.org/10.1128/AAC.48.8.3175-3178.2004] [PMID: 15273144]
[41]
Paulsen IT, Chen J, Nelson KE, Saier MH Jr. Comparative genomics of microbial drug efflux systems. J Mol Microbiol Biotechnol 2001; 3(2): 145-50.
[PMID: 11321566]
[42]
Saurin W, Hofnung M, Dassa E. Getting in or out: early segregation between importers and exporters in the evolution of ATP-binding cassette (ABC) transporters. J Mol Evol 1999; 48(1): 22-41.
[http://dx.doi.org/10.1007/PL00006442] [PMID: 9873074]
[43]
Ehrmann M, Ehrle R, Hofmann E, Boos W, Schlösser A. The ABC maltose transporter. Mol Microbiol 1998; 29(3): 685-94.
[http://dx.doi.org/10.1046/j.1365-2958.1998.00915.x] [PMID: 9723909]
[44]
Alloing G, de Philip P, Claverys JP. Three highly homologous membrane-bound lipoproteins participate in oligopeptide transport by the Ami system of the gram-positive Streptococcus pneumoniae. J Mol Biol 1994; 241(1): 44-58.
[http://dx.doi.org/10.1006/jmbi.1994.1472] [PMID: 8051706]
[45]
Ames GF, Mimura CS, Shyamala V. Bacterial periplasmic permeases belong to a family of transport proteins operating from Escherichia coli to human: Traffic ATPases. FEMS Microbiol Rev 1990; 6(4): 429-46.
[http://dx.doi.org/10.1016/S0168-6445(05)80008-7] [PMID: 2147378]
[46]
Gilson E, Alloing G, Schmidt T, Claverys JP, Dudler R, Hofnung M. Evidence for high affinity binding-protein dependent transport systems in gram-positive bacteria and in Mycoplasma. EMBO J 1988; 7(12): 3971-4.
[http://dx.doi.org/10.1002/j.1460-2075.1988.tb03284.x] [PMID: 3208757]
[47]
Braibant M, Gilot P, Content J. The ATP binding cassette (ABC) transport systems of Mycobacterium tuberculosis. FEMS Microbiol Rev 2000; 24(4): 449-67.
[http://dx.doi.org/10.1111/j.1574-6976.2000.tb00550.x] [PMID: 10978546]
[48]
Balganesh M, Kuruppath S, Marcel N, Sharma S, Nair A, Sharma U. Rv1218c, an ABC transporter of Mycobacterium tuberculosis with implications in drug discovery. Antimicrob Agents Chemother 2010; 54(12): 5167-72.
[http://dx.doi.org/10.1128/AAC.00610-10] [PMID: 20921309]
[49]
Piddock LJ. Clinically relevant chromosomally encoded multidrug resistance efflux pumps in bacteria. Clin Microbiol Rev 2006; 19(2): 382-402.
[http://dx.doi.org/10.1128/CMR.19.2.382-402.2006] [PMID: 16614254]
[50]
Abedinzadeh M, Gaeini M, Sardari S. Natural antimicrobial peptides against Mycobacterium tuberculosis. J Antimicrob Chemother 2015; 70(5): 1285-9.
[http://dx.doi.org/10.1093/jac/dku570] [PMID: 25681127]
[51]
Arranz-Trullén J, Lu L, Pulido D, Bhakta S, Boix E. Host antimicrobial peptides: The promise of new treatment strategies against tuberculosis. Front Immunol 2017; 8: 1499.
[http://dx.doi.org/10.3389/fimmu.2017.01499] [PMID: 29163551]
[52]
Clare JJ. Targeting ion channels for drug discovery. Discov Med 2010; 9(46): 253-60.
[PMID: 20350493]
[53]
Overington JP, Al-Lazikani B, Hopkins AL. How many drug targets are there? Nat Rev Drug Discov 2006; 5(12): 993-6.
[http://dx.doi.org/10.1038/nrd2199] [PMID: 17139284]
[54]
Youm J, Saier MH Jr, Saier MH Jr. Comparative analyses of transport proteins encoded within the genomes of Mycobacterium tuberculosis and Mycobacterium leprae. Biochim Biophys Acta 2012; 1818(3): 776-97.
[http://dx.doi.org/10.1016/j.bbamem.2011.11.015] [PMID: 22179038]
[55]
Abate G, Ruminiski PG, Kumar M, et al. New verapamil analogs inhibit intracellular mycobacteria without affecting the functions of mycobacterium-specific T cells. Antimicrob Agents Chemother 2015; 60(3): 1216-25.
[http://dx.doi.org/10.1128/AAC.01567-15] [PMID: 26643325]
[56]
Agranoff D, Krishna S. Metal ion transport and regulation in Mycobacterium tuberculosis. Front Biosci 2004; 9: 2996-3006.
[http://dx.doi.org/10.2741/1454] [PMID: 15353332]
[57]
Song H, Sandie R, Wang Y, Andrade-Navarro MA, Niederweis M. Identification of outer membrane proteins of Mycobacterium tuberculosis. Tuberculosis (Edinb) 2008; 88(6): 526-44.
[http://dx.doi.org/10.1016/j.tube.2008.02.004] [PMID: 18439872]
[58]
Esnouf RM. An extensively modified version of MolScript that includes greatly enhanced coloring capabilities. J Mol Graph Model 1997; 15(2): 132-4. 112-113
[http://dx.doi.org/10.1016/S1093-3263(97)00021-1] [PMID: 9385560]
[59]
Kraulis PJ. Molscript: A program to produce both detailed and schematic plots of protein structure. J Appl Cryst 1991; 24: 946-50.
[http://dx.doi.org/10.1107/S0021889891004399]
[60]
Merritt EA, Bacon DJ. Raster3D: photorealistic molecular graphics. Methods Enzymol 1997; 277: 505-24.
[http://dx.doi.org/10.1016/S0076-6879(97)77028-9] [PMID: 18488322]

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