Abstract
Background: Mycolic acids (MAs) are the characteristic, integral building blocks for the mycomembrane belonging to the insidious bacterial pathogen Mycobacterium tuberculosis (M.tb). These C60-C90 long α-alkyl-β-hydroxylated fatty acids provide protection to the tubercle bacilli against the outside threats, thus allowing its survival, virulence and resistance to the current antibacterial agents. In the post-genomic era, progress has been made towards understanding the crucial enzymatic machineries involved in the biosynthesis of MAs in M.tb. However, gaps still remain in the exact role of the phosphorylation and dephosphorylation of regulatory mechanisms within these systems. To date, a total of 11 serine-threonine protein kinases (STPKs) are found in M.tb. Most enzymes implicated in the MAs synthesis were found to be phosphorylated in vitro and/or in vivo. For instance, phosphorylation of KasA, KasB, mtFabH, InhA, MabA, and FadD32 downregulated their enzymatic activity, while phosphorylation of VirS increased its enzymatic activity. These observations suggest that the kinases and phosphatases system could play a role in M.tb adaptive responses and survival mechanisms in the human host. As the mycobacterial STPKs do not share a high sequence homology to the human’s, there have been some early drug discovery efforts towards developing potent and selective inhibitors.
Objective: Recent updates to the kinases and phosphatases involved in the regulation of MAs biosynthesis will be presented in this mini-review, including their known small molecule inhibitors.
Conclusion: Mycobacterial kinases and phosphatases involved in the MAs regulation may serve as a useful avenue for antitubercular therapy.
Keywords: Mycobacterium, tuberculosis, kinase, phosphatase, mycolic acids, small molecule inhibitors, formulations.
Graphical Abstract
[2]
Tiberi, S.; Scardigli, A.; Centis, R.; D’Ambrosio, L.; Munoz-Torrico, M.; Salazar-Lezama, M.A.; Spanevello, A.; Visca, D.; Zumla, A.; Migliori, G.B.; Caminero Luna, J.A. Classifying new anti-tuberculosis drugs: Rationale and future perspectives. Int. J. Infect. Dis., 2017, 56, 181-184.
[3]
Al-Humadi, H.W.; Al-Saigh, R.J.; Al-Humadi, A.W. Addressing the challenges of tuberculosis: A brief historical account. Front. Pharmacol., 2017, 8, 689.
[http://dx.doi.org/10.3389/fphar.2017.00689]
[http://dx.doi.org/10.3389/fphar.2017.00689]
[4]
Caminero, J.A. World Health, O.; American Thoracic, S.; British Thoracic, S. Treatment of multidrug-resistant tuberculosis: Evidence and controversies. Int. J. Tuberc. Lung Dis., 2006, 10(8), 829-837.
[5]
Chan, E.D.; Laurel, V.; Strand, M.J.; Chan, J.F.; Huynh, M.L.; Goble, M.; Iseman, M.D. Treatment and outcome analysis of 205 patients with multidrug-resistant tuberculosis. Am. J. Respir. Crit. Care Med., 2004, 169(10), 1103-1109.
[6]
Eker, B.; Ortmann, J.; Migliori, G.B.; Sotgiu, G.; Muetterlein, R.; Centis, R.; Hoffmann, H.; Kirsten, D.; Schaberg, T.; Ruesch-Gerdes, S.; Lange, C.; German, T.G. Multidrug- and extensively drug-resistant tuberculosis, Germany. Emerg. Infect. Dis., 2008, 14(11), 1700-1706.
[7]
Migliori, G.B.; Loddenkemper, R.; Blasi, F.; Raviglione, M.C. 125 years after Robert Koch’s discovery of the Tubercle bacillus: The new XDR-TB threat. Is “science” enough to tackle the epidemic? Eur. Respir. J., 2007, 29(3), 423-427.
[8]
Mitnick, C.D.; Shin, S.S.; Seung, K.J.; Rich, M.L.; Atwood, S.S.; Furin, J.J.; Fitzmaurice, G.M.; Alcantara Viru, F.A.; Appleton, S.C.; Bayona, J.N.; Bonilla, C.A.; Chalco, K.; Choi, S.; Franke, M.F.; Fraser, H.S.; Guerra, D.; Hurtado, R.M.; Jazayeri, D.; Joseph, K.; Llaro, K.; Mestanza, L.; Mukherjee, J.S.; Munoz, M.; Palacios, E.; Sanchez, E.; Sloutsky, A.; Becerra, M.C. Comprehensive treatment of extensively drug-resistant tuberculosis. N. Engl. J. Med., 2008, 359(6), 563-574.
[9]
Velayati, A.A.; Farnia, P.; Masjedi, M.R. The totally drug resistant tuberculosis (TDR-TB). Int. J. Clin. Exp. Med., 2013, 6(4), 307-309.
[10]
Sotgiu, G.; Centis, R.; D’Ambrosio, L.; Migliori, G.B. Tuberculosis treatment and drug regimens. Cold Spring Harb. Perspect. Med., 2015, 5(5), a017822.
[11]
Cole, S.T.; Brosch, R.; Parkhill, J.; Garnier, T.; Churcher, C.; Harris, D.; Gordon, S.V.; Eiglmeier, K.; Gas, S.; Barry, C.E., 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.; Krogh, A.; McLean, J.; Moule, S.; Murphy, L.; Oliver, K.; Osborne, J.; Quail, M.A.; Rajandream, M.A.; Rogers, J.; Rutter, S.; Seeger, K.; Skelton, J.; Squares, R.; Squares, S.; Sulston, J.E.; Taylor, K.; Whitehead, S.; Barrell, B.G. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature, 1998, 393(6685), 537-544.
[12]
Takayama, K.; Wang, C.; Besra, G.S. Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. Clin. Microbiol. Rev., 2005, 18(1), 81-101.
[13]
Takayama, K.; Wang, L.; David, H.L. Effect of isoniazid on the in vivo mycolic acid synthesis, cell growth, and viability of Mycobacterium tuberculosis. Antimicrob. Agents Chemother., 1972, 2(1), 29-35.
[14]
Molle, V.; Kremer, L. Division and cell envelope regulation by Ser/Thr phosphorylation: Mycobacterium shows the way. Mol. Microbiol., 2010, 75(5), 1064-1077.
[15]
Daffe, M.; Crick, D.C.; Jackson, M. Genetics of Capsular Polysaccharides and Cell Envelope (Glyco)lipids Microbiol. Spectr., 2014, 2(4), MGM2-0021-2013.
[16]
Jackson, M.; Stadthagen, G.; Gicquel, B. Long-chain multiple methyl-branched fatty acid-containing lipids of Mycobacterium tuberculosis: Biosynthesis, transport, regulation and biological activities. Tuberculosis (Edinb.), 2007, 87(2), 78-86.
[17]
Nataraj, V.; Varela, C.; Javid, A.; Singh, A.; Besra, G.S.; Bhatt, A. Mycolic acids: Deciphering and targeting the Achilles’ heel of the Tubercle bacillus. Mol. Microbiol., 2015, 98(1), 7-16.
[18]
Lederer, E.; Adam, A.; Ciorbaru, R.; Petit, J.F.; Wietzerbin, J. Cell walls of Mycobacteria and related organisms; Chemistry and immunostimulant properties. Mol. Cell. Biochem., 1975, 7(2), 87-104.
[20]
Misaki, A.; Seto, N.; Azuma, I. Structure and immunological properties of D-arabino-D-galactans isolated from cell walls of Mycobacterium species. J. Biochem., 1974, 76(1), 15-27.
[21]
Azuma, I.; Yamamura, Y. Studies on the firmly bound lipids of human Tubercle bacillus. J. Biochem., 1963, 53, 275-281.
[22]
Daffe, M.; Draper, P. The envelope layers of mycobacteria with reference to their pathogenicity. Adv. Microb. Physiol., 1998, 39, 131-203.
[23]
Hattori, Y.; Matsunaga, I.; Komori, T.; Urakawa, T.; Nakamura, T.; Fujiwara, N.; Hiromatsu, K.; Harashima, H.; Sugita, M. Glycerol monomycolate, a latent tuberculosis-associated mycobacterial lipid, induces eosinophilic hypersensitivity responses in guinea pigs. Biochem. Biophys. Res. Commun., 2011, 409(2), 304-307.
[24]
McNeil, M.R.; Brennan, P.J. Structure, function and biogenesis of the cell envelope of mycobacteria in relation to bacterial physiology, pathogenesis and drug resistance; Some thoughts and possibilities arising from recent structural information. Res. Microbiol., 1991, 142(4), 451-463.
[25]
Roura-Mir, C.; Wang, L.; Cheng, T.Y.; Matsunaga, I.; Dascher, C.C.; Peng, S.L.; Fenton, M.J.; Kirschning, C.; Moody, D.B. Mycobacterium tuberculosis regulates CD1 antigen presentation pathways through TLR-2. J. Immunol., 2005, 175(3), 1758-1766.
[26]
Geisel, R.E.; Sakamoto, K.; Russell, D.G.; Rhoades, E.R. In vivo activity of released cell wall lipids of Mycobacterium bovis bacillus Calmette-Guerin is due principally to trehalose mycolates. J. Immunol., 2005, 174(8), 5007-5015.
[27]
Layre, E.; Collmann, A.; Bastian, M.; Mariotti, S.; Czaplicki, J.; Prandi, J.; Mori, L.; Stenger, S.; De Libero, G.; Puzo, G.; Gilleron, M. Mycolic acids constitute a scaffold for mycobacterial lipid antigens stimulating CD1-restricted T cells. Chem. Biol., 2009, 16(1), 82-92.
[28]
Moody, D.B.; Briken, V.; Cheng, T.Y.; Roura-Mir, C.; Guy, M.R.; Geho, D.H.; Tykocinski, M.L.; Besra, G.S.; Porcelli, S.A. Lipid length controls antigen entry into endosomal and nonendosomal pathways for CD1b presentation. Nat. Immunol., 2002, 3(5), 435-442.
[29]
Hunter, R.L.; Venkataprasad, N.; Olsen, M.R. The role of trehalose dimycolate (cord factor) on morphology of virulent M. tuberculosis in vitro. Tuberculosis (Edinb.), 2006, 86(5), 349-356.
[30]
Hunter, R.L.; Olsen, M.; Jagannath, C.; Actor, J.K. Trehalose 6,6′-dimycolate and lipid in the pathogenesis of caseating granulomas of tuberculosis in mice. Am. J. Pathol., 2006, 168(4), 1249-1261.
[31]
Marrakchi, H.; Laneelle, M.A.; Daffe, M. Mycolic acids: Structures, biosynthesis, and beyond. Chem. Biol., 2014, 21(1), 67-85.
[32]
Raman, K.; Rajagopalan, P.; Chandra, N. Flux balance analysis of mycolic acid pathway: Targets for anti-tubercular drugs. PLoS Comput. Biol., 2005, 1(5), e46.
[33]
Barry, C.E., 3rd; Lee, R.E.; Mdluli, K.; Sampson, A.E.; Schroeder, B.G.; Slayden, R.A.; Yuan, Y. Mycolic acids: Structure, biosynthesis and physiological functions. Prog. Lipid Res., 1998, 37(2-3), 143-179.
[34]
Bhatt, A.; Molle, V.; Besra, G.S.; Jacobs, W.R., Jr; Kremer, L. The Mycobacterium tuberculosis FAS-II condensing enzymes: Their role in mycolic acid biosynthesis, acid-fastness, pathogenesis and in future drug development. Mol. Microbiol., 2007, 64(6), 1442-1454.
[35]
Bloch, K. Control mechanisms for fatty acid synthesis in Mycobacterium smegmatis. Adv. Enzymol. Relat. Areas Mol. Biol., 1977, 45, 1-84.
[36]
Daniel, J.; Oh, T.J.; Lee, C.M.; Kolattukudy, P.E. AccD6, a member of the Fas II locus, is a functional carboxyltransferase subunit of the acyl-coenzyme A carboxylase in Mycobacterium tuberculosis. J. Bacteriol., 2007, 189(3), 911-917.
[37]
Bloch, K.; Vance, D. Control mechanisms in the synthesis of saturated fatty acids. Annu. Rev. Biochem., 1977, 46, 263-298.
[38]
Fernandes, N.D.; Kolattukudy, P.E. Cloning, sequencing and characterization of a fatty acid synthase-encoding gene from Mycobacterium tuberculosis var. bovis BCG. Gene, 1996, 170(1), 95-99.
[39]
Zimhony, O.; Vilcheze, C.; Jacobs, W.R., Jr Characterization of Mycobacterium smegmatis expressing the Mycobacterium tuberculosis fatty acid synthase I (fas1) gene. J. Bacteriol., 2004, 186(13), 4051-4055.
[40]
Smith, S.; Witkowski, A.; Joshi, A.K. Structural and functional organization of the animal fatty acid synthase. Prog. Lipid Res., 2003, 42(4), 289-317.
[41]
Odriozola, J.M.; Ramos, J.A.; Bloch, K. Fatty acid synthetase activity in Mycobacterium smegmatis. Characterization of the acyl carrier protein-dependent elongating system. Biochim. Biophys. Acta, 1977, 488(2), 207-217.
[42]
Kremer, L.; Nampoothiri, K.M.; Lesjean, S.; Dover, L.G.; Graham, S.; Betts, J.; Brennan, P.J.; Minnikin, D.E.; Locht, C.; Besra, G.S. Biochemical characterization of acyl carrier protein (AcpM) and malonyl-CoA:AcpM transacylase (mtFabD), two major components of Mycobacterium tuberculosis fatty acid synthase II. J. Biol. Chem., 2001, 276(30), 27967-27974.
[43]
Choi, K.H.; Kremer, L.; Besra, G.S.; Rock, C.O. Identification and substrate specificity of beta -ketoacyl (acyl carrier protein) synthase III (mtFabH) from Mycobacterium tuberculosis. J. Biol. Chem., 2000, 275(36), 28201-28207.
[44]
Marrakchi, H.; Ducasse, S.; Labesse, G.; Montrozier, H.; Margeat, E.; Emorine, L.; Charpentier, X.; Daffe, M.; Quemard, A. MabA (FabG1), a Mycobacterium tuberculosis protein involved in the long-chain fatty acid elongation system FAS-II. Microbiology, 2002, 148(Pt 4), 951-960.
[45]
Bhatt, A.; Fujiwara, N.; Bhatt, K.; Gurcha, S.S.; Kremer, L.; Chen, B.; Chan, J.; Porcelli, S.A.; Kobayashi, K.; Besra, G.S.; Jacobs, W.R., Jr Deletion of kasB in Mycobacterium tuberculosis causes loss of acid-fastness and subclinical latent tuberculosis in immunocompetent mice. Proc. Natl. Acad. Sci. USA, 2007, 104(12), 5157-5162.
[46]
Bhatt, A.; Kremer, L.; Dai, A.Z.; Sacchettini, J.C.; Jacobs, W.R., Jr Conditional depletion of KasA, a key enzyme of mycolic acid biosynthesis, leads to mycobacterial cell lysis. J. Bacteriol., 2005, 187(22), 7596-7606.
[47]
Kremer, L.; Dover, L.G.; Carrere, S.; Nampoothiri, K.M.; Lesjean, S.; Brown, A.K.; Brennan, P.J.; Minnikin, D.E.; Locht, C.; Besra, G.S. Mycolic acid biosynthesis and enzymic characterization of the beta-ketoacyl-ACP synthase A-condensing enzyme from Mycobacterium tuberculosis. Biochem. J., 2002, 364(Pt 2), 423-430.
[48]
Schaeffer, M.L.; Agnihotri, G.; Volker, C.; Kallender, H.; Brennan, P.J.; Lonsdale, J.T. Purification and biochemical characterization of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthases KasA and KasB. J. Biol. Chem., 2001, 276(50), 47029-47037.
[49]
Slayden, R.A.; Barry, C.E., 3rd The role of KasA and KasB in the biosynthesis of meromycolic acids and isoniazid resistance in Mycobacterium tuberculosis. Tuberculosis (Edinb.), 2002, 82(4-5), 149-160.
[50]
Cantaloube, S.; Veyron-Churlet, R.; Haddache, N.; Daffe, M.; Zerbib, D. The Mycobacterium tuberculosis FAS-II dehydratases and methyltransferases define the specificity of the mycolic acid elongation complexes. PLoS One, 2011, 6(12), e29564.
[51]
Veyron-Churlet, R.; Bigot, S.; Guerrini, O.; Verdoux, S.; Malaga, W.; Daffe, M.; Zerbib, D. The biosynthesis of mycolic acids in Mycobacterium tuberculosis relies on multiple specialized elongation complexes interconnected by specific protein-protein interactions. J. Mol. Biol., 2005, 353(4), 847-858.
[52]
Veyron-Churlet, R.; Guerrini, O.; Mourey, L.; Daffe, M.; Zerbib, D. Protein-protein interactions within the Fatty Acid Synthase-II system of Mycobacterium tuberculosis are essential for mycobacterial viability. Mol. Microbiol., 2004, 54(5), 1161-1172.
[53]
Marrakchi, H. Bardou, F.; Lanéelle, M.-a.; Daffé, M. In: The Mycobacterial Cell Envelope; American Society of Microbiology, 2008.
[54]
Sacco, E.; Covarrubias, A.S.; O’Hare, H.M.; Carroll, P.; Eynard, N.; Jones, T.A.; Parish, T.; Daffe, M.; Backbro, K.; Quemard, A. The missing piece of the type II fatty acid synthase system from Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA, 2007, 104(37), 14628-14633.
[55]
Gao, L.Y.; Laval, F.; Lawson, E.H.; Groger, R.K.; Woodruff, A.; Morisaki, J.H.; Cox, J.S.; Daffe, M.; Brown, E.J. Requirement for kasB in Mycobacterium mycolic acid biosynthesis, cell wall impermeability and intracellular survival: Implications for therapy. Mol. Microbiol., 2003, 49(6), 1547-1563.
[56]
Gokhale, R.S.; Saxena, P.; Chopra, T.; Mohanty, D. Versatile polyketide enzymatic machinery for the biosynthesis of complex mycobacterial lipids. Nat. Prod. Rep., 2007, 24(2), 267-277.
[57]
Trivedi, O.A.; Arora, P.; Sridharan, V.; Tickoo, R.; Mohanty, D.; Gokhale, R.S. Enzymic activation and transfer of fatty acids as acyl-adenylates in mycobacteria. Nature, 2004, 428(6981), 441-445.
[58]
Gavalda, S.; Bardou, F.; Laval, F.; Bon, C.; Malaga, W.; Chalut, C.; Guilhot, C.; Mourey, L.; Daffe, M.; Quemard, A. The polyketide synthase Pks13 catalyzes a novel mechanism of lipid transfer in mycobacteria. Chem. Biol., 2014, 21(12), 1660-1669.
[59]
Gavalda, S.; Leger, M.; van der Rest, B.; Stella, A.; Bardou, F.; Montrozier, H.; Chalut, C.; Burlet-Schiltz, O.; Marrakchi, H.; Daffe, M.; Quemard, A. The Pks13/FadD32 crosstalk for the biosynthesis of mycolic acids in Mycobacterium tuberculosis. J. Biol. Chem., 2009, 284(29), 19255-19264.
[60]
Leger, M.; Gavalda, S.; Guillet, V.; van der Rest, B.; Slama, N.; Montrozier, H.; Mourey, L.; Quemard, A.; Daffe, M.; Marrakchi, H. The dual function of the Mycobacterium tuberculosis FadD32 required for mycolic acid biosynthesis. Chem. Biol., 2009, 16(5), 510-519.
[61]
Gande, R.; Gibson, K.J.; Brown, A.K.; Krumbach, K.; Dover, L.G.; Sahm, H.; Shioyama, S.; Oikawa, T.; Besra, G.S.; Eggeling, L. Acyl-CoA carboxylases (accD2 and accD3), together with a unique polyketide synthase (Cg-pks), are key to mycolic acid biosynthesis in Corynebacterianeae such as Corynebacterium glutamicum and Mycobacterium tuberculosis. J. Biol. Chem., 2004, 279(43), 44847-44857.
[62]
Portevin, D.; De Sousa-D’Auria, C.; Houssin, C.; Grimaldi, C.; Chami, M.; Daffe, M.; Guilhot, C. A polyketide synthase catalyzes the last condensation step of mycolic acid biosynthesis in mycobacteria and related organisms. Proc. Natl. Acad. Sci. USA, 2004, 101(1), 314-319.
[63]
Portevin, D.; de Sousa-D’Auria, C.; Montrozier, H.; Houssin, C.; Stella, A.; Laneelle, M.A.; Bardou, F.; Guilhot, C.; Daffe, M. The acyl-AMP ligase FadD32 and AccD4-containing acyl-CoA carboxylase are required for the synthesis of mycolic acids and essential for mycobacterial growth: Identification of the carboxylation product and determination of the acyl-CoA carboxylase components. J. Biol. Chem., 2005, 280(10), 8862-8874.
[64]
Bhatt, A.; Brown, A.K.; Singh, A.; Minnikin, D.E.; Besra, G.S. Loss of a mycobacterial gene encoding a reductase leads to an altered cell wall containing beta-oxo-mycolic acid analogs and accumulation of ketones. Chem. Biol., 2008, 15(9), 930-939.
[65]
Lea-Smith, D.J.; Pyke, J.S.; Tull, D.; McConville, M.J.; Coppel, R.L.; Crellin, P.K. The reductase that catalyzes mycolic motif synthesis is required for efficient attachment of mycolic acids to arabinogalactan. J. Biol. Chem., 2007, 282(15), 11000-11008.
[66]
Aggarwal, A.; Parai, M.K.; Shetty, N.; Wallis, D.; Woolhiser, L.; Hastings, C.; Dutta, N.K.; Galaviz, S.; Dhakal, R.C.; Shrestha, R.; Wakabayashi, S.; Walpole, C.; Matthews, D.; Floyd, D.; Scullion, P.; Riley, J.; Epemolu, O.; Norval, S.; Snavely, T.; Robertson, G.T.; Rubin, E.J.; Ioerger, T.R.; Sirgel, F.A.; van der Merwe, R.; van Helden, P.D.; Keller, P.; Bottger, E.C.; Karakousis, P.C.; Lenaerts, A.J.; Sacchettini, J.C. Development of a Novel Lead that Targets M. tuberculosis Polyketide Synthase 13. Cell, 2017, 170(2), 249-259 . e225
[67]
Bergeret, F.; Gavalda, S.; Chalut, C.; Malaga, W.; Quemard, A.; Pedelacq, J.D.; Daffe, M.; Guilhot, C.; Mourey, L.; Bon, C. Biochemical and structural study of the atypical acyltransferase domain from the mycobacterial polyketide synthase Pks13. J. Biol. Chem., 2012, 287(40), 33675-33690.
[68]
Yu, M.; Dou, C.; Gu, Y.; Cheng, W. Crystallization and structure analysis of the core motif of the Pks13 acyltransferase domain from Mycobacterium tuberculosis. PeerJ, 2018, 6, e4728.
[69]
Thanna, S.; Knudson, S.E.; Grzegorzewicz, A.; Kapil, S.; Goins, C.M.; Ronning, D.R.; Jackson, M.; Slayden, R.A.; Sucheck, S.J. Synthesis and evaluation of new 2-aminothiophenes against Mycobacterium tuberculosis. Org. Biomol. Chem., 2016, 14(25), 6119-6133.
[70]
Zhang, W.; Lun, S.; Wang, S.H.; Jiang, X.W.; Yang, F.; Tang, J.; Manson, A.L.; Earl, A.M.; Gunosewoyo, H.; Bishai, W.R.; Yu, L.F. Identification of Novel Coumestan Derivatives as Polyketide Synthase 13 Inhibitors against Mycobacterium tuberculosis. J. Med. Chem., 2018, 61(3), 791-803.
[71]
Domenech, P.; Reed, M.B.; Barry, C.E., 3rd Contribution of the Mycobacterium tuberculosis MmpL protein family to virulence and drug resistance. Infect. Immun., 2005, 73(6), 3492-3501.
[72]
Belardinelli, J.M.; Larrouy-Maumus, G.; Jones, V.; Sorio de Carvalho, L.P.; McNeil, M.R.; Jackson, M. Biosynthesis and translocation of unsulfated acyltrehaloses in Mycobacterium tuberculosis. J. Biol. Chem., 2014, 289(40), 27952-27965.
[73]
Converse, S.E.; Mougous, J.D.; Leavell, M.D.; Leary, J.A.; Bertozzi, C.R.; Cox, J.S. MmpL8 is required for sulfolipid-1 biosynthesis and Mycobacterium tuberculosis virulence. Proc. Natl. Acad. Sci. USA, 2003, 100(10), 6121-6126.
[74]
Cox, J.S.; Chen, B.; McNeil, M.; Jacobs, W.R., Jr Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice. Nature, 1999, 4020(6757), 79-83.
[75]
Domenech, P.; Reed, M.B.; Dowd, C.S.; Manca, C.; Kaplan, G.; Barry, C.E., 3rd The role of MmpL8 in sulfatide biogenesis and virulence of Mycobacterium tuberculosis. J. Biol. Chem., 2004, 279(20), 21257-21265.
[76]
Xu, Z.; Meshcheryakov, V.A.; Poce, G.; Chng, S.S. MmpL3 is the flippase for mycolic acids in mycobacteria. Proc. Natl. Acad. Sci. USA, 2017, 114(30), 7993-7998.
[77]
Mdluli, K.; Kaneko, T.; Upton, A. Tuberculosis drug discovery and emerging targets. Ann. N. Y. Acad. Sci., 2014, 1323, 56-75.
[78]
Owens, C.P.; Chim, N.; Graves, A.B.; Harmston, C.A.; Iniguez, A.; Contreras, H.; Liptak, M.D.; Goulding, C.W. The Mycobacterium tuberculosis secreted protein Rv0203 transfers heme to membrane proteins MmpL3 and MmpL11. J. Biol. Chem., 2013, 288(30), 21714-21728.
[79]
Grzegorzewicz, A.E.; Pham, H.; Gundi, V.A.; Scherman, M.S.; North, E.J.; Hess, T.; Jones, V.; Gruppo, V.; Born, S.E.; Kordulakova, J.; Chavadi, S.S.; Morisseau, C.; Lenaerts, A.J.; Lee, R.E.; McNeil, M.R.; Jackson, M. Inhibition of mycolic acid transport across the Mycobacterium tuberculosis plasma membrane. Nat. Chem. Biol., 2012, 8(4), 334-341.
[80]
Tahlan, K.; Wilson, R.; Kastrinsky, D.B.; Arora, K.; Nair, V.; Fischer, E.; Barnes, S.W.; Walker, J.R.; Alland, D.; Barry, C.E., 3rd; Boshoff, H.I. SQ109 targets MmpL3, a membrane transporter of trehalose monomycolate involved in mycolic acid donation to the cell wall core of Mycobacterium tuberculosis. Antimicrob. Agents Chemother., 2012, 56(4), 1797-1809.
[81]
Varela, C.; Rittmann, D.; Singh, A.; Krumbach, K.; Bhatt, K.; Eggeling, L.; Besra, G.S.; Bhatt, A. MmpL genes are associated with mycolic acid metabolism in mycobacteria and corynebacteria. Chem. Biol., 2012, 19(4), 498-506.
[82]
Warrier, T.; Tropis, M.; Werngren, J.; Diehl, A.; Gengenbacher, M.; Schlegel, B.; Schade, M.; Oschkinat, H.; Daffe, M.; Hoffner, S.; Eddine, A.N.; Kaufmann, S.H. Antigen 85C inhibition restricts Mycobacterium tuberculosis growth through disruption of cord factor biosynthesis. Antimicrob. Agents Chemother., 2012, 56(4), 1735-1743.
[83]
Stock, J.B.; Ninfa, A.J.; Stock, A.M. Protein phosphorylation and regulation of adaptive responses in bacteria. Microbiol. Rev., 1989, 53(4), 450-490.
[84]
Prisic, S.; Husson, R.N. Mycobacterium tuberculosis Serine/Threonine Protein Kinases. Microbiol. Spectrum., 2014, 2(5), 1-26.
[85]
Parish, T. Two-Component Regulatory Systems of Mycobacteria. Microbiol. Spectr., 2014, 2(1), MGM2-0010-2013.
[86]
Richard-Greenblatt, M.; Av-Gay, Y. Epigenetic Phosphorylation Control of Mycobacterium tuberculosis Infection and Persistence. Microbiol. Spectr., 2017, 5(2)
[http://dx.doi.org/10.1128/microbiolspec.TBTB2-0005-2015]
[http://dx.doi.org/10.1128/microbiolspec.TBTB2-0005-2015]
[87]
Av-Gay, Y.; Everett, M. The eukaryotic-like Ser/Thr protein kinases of Mycobacterium tuberculosis. Trends Microbiol., 2000, 8(5), 238-244.
[88]
Greenstein, A.E.; Grundner, C.; Echols, N.; Gay, L.M.; Lombana, T.N.; Miecskowski, C.A.; Pullen, K.E.; Sung, P.Y.; Alber, T. Structure/function studies of Ser/Thr and Tyr protein phosphorylation in Mycobacterium tuberculosis. J. Mol. Microbiol. Biotechnol., 2005, 9(3-4), 167-181.
[89]
Wehenkel, A.; Bellinzoni, M.; Grana, M.; Duran, R.; Villarino, A.; Fernandez, P.; Andre-Leroux, G.; England, P.; Takiff, H.; Cervenansky, C.; Cole, S.T.; Alzari, P.M. Mycobacterial Ser/Thr protein kinases and phosphatases: physiological roles and therapeutic potential. Biochim. Biophys. Acta, 2008, 1784(1), 193-202.
[90]
Zhou, P.; Long, Q.; Zhou, Y.; Wang, H.; Xie, J. Mycobacterium tuberculosis two-component systems and implications in novel vaccines and drugs. Crit. Rev. Eukaryot. Gene Expr., 2012, 22(1), 37-52.
[91]
Canova, M.J.; Molle, V. Bacterial serine/threonine protein kinases in host-pathogen interactions. J. Biol. Chem., 2014, 289(14), 9473-9479.
[92]
Narayan, A.; Sachdeva, P.; Sharma, K.; Saini, A.K.; Tyagi, A.K.; Singh, Y. Serine threonine protein kinases of mycobacterial genus: Phylogeny to function. Physiol. Genomics, 2007, 29(1), 66-75.
[93]
Prisic, S.; Dankwa, S.; Schwartz, D.; Chou, M.F.; Locasale, J.W.; Kang, C.M.; Bemis, G.; Church, G.M.; Steen, H.; Husson, R.N. Extensive phosphorylation with overlapping specificity by Mycobacterium tuberculosis serine/threonine protein kinases. Proc. Natl. Acad. Sci. USA, 2010, 107(16), 7521-7526.
[94]
Huse, M.; Kuriyan, J. The conformational plasticity of protein kinases. Cell, 2002, 109(3), 275-282.
[96]
Braconi Quintaje, S.; Orchard, S. The annotation of both human and mouse kinomes in UniProtKB/Swiss-Prot: One small step in manual annotation, one giant leap for full comprehension of genomes. Mol. Cell. Proteomics, 2008, 7(8), 1409-1419.
[97]
Manning, G.; Whyte, D.B.; Martinez, R.; Hunter, T.; Sudarsanam, S. The protein kinase complement of the human genome. Science, 2002, 298(5600), 1912-1934.
[98]
Bach, H.; Wong, D.; Av-Gay, Y. Mycobacterium tuberculosis PtkA is a novel protein tyrosine kinase whose substrate is PtpA. Biochem. J., 2009, 420(2), 155-160.
[99]
Zhou, P.; Li, W.; Wong, D.; Xie, J.; Av-Gay, Y. Phosphorylation control of protein tyrosine phosphatase A activity in Mycobacterium tuberculosis. FEBS Lett., 2015, 589(3), 326-331.
[100]
Wong, D.; Li, W.; Chao, J.D.; Zhou, P.; Narula, G.; Tsui, C.; Ko, M.; Xie, J.; Martinez-Frailes, C.; Av-Gay, Y. Protein tyrosine kinase, PtkA, is required for Mycobacterium tuberculosis growth in macrophages. Sci. Rep., 2018, 8(1), 155.
[http://dx.doi.org/10.1038/s41598-017-18547-9]
[http://dx.doi.org/10.1038/s41598-017-18547-9]
[101]
Sajid, A.; Arora, G.; Singhal, A.; Kalia, V.C.; Singh, Y. Protein Phosphatases of Pathogenic Bacteria: Role in Physiology and Virulence. Annu. Rev. Microbiol., 2015, 69, 527-547.
[102]
Boitel, B.; Ortiz-Lombardia, M.; Duran, R.; Pompeo, F.; Cole, S.T.; Cervenansky, C.; Alzari, P.M. PknB kinase activity is regulated by phosphorylation in two Thr residues and dephosphorylation by PstP, the cognate phospho-Ser/Thr phosphatase, in Mycobacterium tuberculosis. Mol. Microbiol., 2003, 49(6), 1493-1508.
[103]
Chopra, P.; Singh, B.; Singh, R.; Vohra, R.; Koul, A.; Meena, L.S.; Koduri, H.; Ghildiyal, M.; Deol, P.; Das, T.K.; Tyagi, A.K.; Singh, Y. Phosphoprotein phosphatase of Mycobacterium tuberculosis dephosphorylates serine-threonine kinases PknA and PknB. Biochem. Biophys. Res. Commun., 2003, 311(1), 112-120.
[104]
Le, N-H.; Molle, V.; Eynard, N.; Miras, M.; Stella, A.; Bardou, F.; Galandrin, S.; Guillet, V.; Andre-Leroux, G.; Bellinzoni, M.; Alzari, P.; Mourey, L.; Burlet-Schiltz, O.; Daffe, M.; Marrakchi, H. Ser/Thr Phosphorylation Regulates the Fatty Acyl-AMP Ligase Activity of FadD32, an Essential Enzyme in Mycolic Acid Biosynthesis. J. Biol. Chem., 2016, 291(43), 22793-22805.
[105]
Sharma, A.K.; Arora, D.; Singh, L.K.; Gangwal, A.; Sajid, A.; Molle, V.; Singh, Y.; Nandicoori, V.K. Serine/Threonine Protein Phosphatase PstP of Mycobacterium tuberculosis Is Necessary for Accurate Cell Division and Survival of Pathogen. J. Biol. Chem., 2016, 291(46), 24215-24230.
[106]
Chao, J.; Wong, D.; Zheng, X.; Poirier, V.; Bach, H.; Hmama, Z.; Av-Gay, Y. Protein kinase and phosphatase signaling in Mycobacterium tuberculosis physiology and pathogenesis. Biochim. Biophys. Acta, 2010, 1804(3), 620-627.
[107]
Koul, A.; Choidas, A.; Treder, M.; Tyagi, A.K.; Drlica, K.; Singh, Y.; Ullrich, A. Cloning and characterization of secretory tyrosine phosphatases of Mycobacterium tuberculosis. J. Bacteriol., 2000, 182(19), 5425-5432.
[108]
Koul, A.; Herget, T.; Klebl, B.; Ullrich, A. Interplay between mycobacteria and host signalling pathways. Nat. Rev. Microbiol., 2004, 2(3), 189-202.
[109]
Zhou, B.; He, Y.; Zhang, X.; Xu, J.; Luo, Y.; Wang, Y.; Franzblau, S.G.; Yang, Z.; Chan, R.J.; Liu, Y.; Zheng, J.; Zhang, Z.Y. Targeting mycobacterium protein tyrosine phosphatase B for antituberculosis agents. Proc. Natl. Acad. Sci. USA, 2010, 107(10), 4573-4578.
[110]
Bach, H.; Papavinasasundaram, K.G.; Wong, D.; Hmama, Z.; Av-Gay, Y. Mycobacterium tuberculosis virulence is mediated by PtpA dephosphorylation of human vacuolar protein sorting 33B. Cell Host Microbe, 2008, 3(5), 316-322.
[111]
Beresford, N.; Patel, S.; Armstrong, J.; Szoor, B.; Fordham-Skelton, A.P.; Tabernero, L. MptpB, a virulence factor from Mycobacterium tuberculosis, exhibits triple-specificity phosphatase activity. Biochem. J., 2007, 406(1), 13-18.
[112]
Castandet, J.; Prost, J.F.; Peyron, P.; Astarie-Dequeker, C.; Anes, E.; Cozzone, A.J.; Griffiths, G.; Maridonneau-Parini, I. Tyrosine phosphatase MptpA of Mycobacterium tuberculosis inhibits phagocytosis and increases actin polymerization in macrophages. Res. Microbiol., 2005, 156(10), 1005-1013.
[113]
Chauhan, P.; Reddy, P.V.; Singh, R.; Jaisinghani, N.; Gandotra, S.; Tyagi, A.K. Secretory phosphatases deficient mutant of Mycobacterium tuberculosis imparts protection at the primary site of infection in guinea pigs. PLoS One, 2013, 8(10), e77930.
[114]
Cowley, S.C.; Babakaiff, R.; Av-Gay, Y. Expression and localization of the Mycobacterium tuberculosis protein tyrosine phosphatase PtpA. Res. Microbiol., 2002, 153(4), 233-241.
[115]
Guler, R.; Brombacher, F. Host-directed drug therapy for tuberculosis. Nat. Chem. Biol., 2015, 11(10), 748-751.
[116]
Singh, R.; Rao, V.; Shakila, H.; Gupta, R.; Khera, A.; Dhar, N.; Singh, A.; Koul, A.; Singh, Y.; Naseema, M.; Narayanan, P.R.; Paramasivan, C.N.; Ramanathan, V.D.; Tyagi, A.K. Disruption of mptpB impairs the ability of Mycobacterium tuberculosis to survive in guinea pigs. Mol. Microbiol., 2003, 50(3), 751-762.
[117]
Singh, R.; Singh, A.; Tyagi, A.K. Deciphering the genes involved in pathogenesis of Mycobacterium tuberculosis. Tuberculosis (Edinb.), 2005, 85(5-6), 325-335.
[118]
Wang, J.; Li, B.X.; Ge, P.P.; Li, J.; Wang, Q.; Gao, G.F.; Qiu, X.B.; Liu, C.H. Mycobacterium tuberculosis suppresses innate immunity by coopting the host ubiquitin system. Nat. Immunol., 2015, 16(3), 237-245.
[119]
Wang, J.; Teng, J.L.; Zhao, D.; Ge, P.; Li, B.; Woo, P.C.; Liu, C.H. The ubiquitin ligase TRIM27 functions as a host restriction factor antagonized by Mycobacterium tuberculosis PtpA during mycobacterial infection. Sci. Rep., 2016, 6, 34827.
[120]
Wong, D.; Bach, H.; Sun, J.; Hmama, Z.; Av-Gay, Y. Mycobacterium tuberculosis protein tyrosine phosphatase (PtpA) excludes host vacuolar-H+-ATPase to inhibit phagosome acidification. Proc. Natl. Acad. Sci. USA, 2011, 108(48), 19371-19376.
[121]
Parrish, N.M.; Dick, J.D.; Bishai, W.R. Mechanisms of latency in Mycobacterium tuberculosis. Trends Microbiol., 1998, 6(3), 107-112.
[122]
Schnappinger, D.; Ehrt, S.; Voskuil, M.I.; Liu, Y.; Mangan, J.A.; Monahan, I.M.; Dolganov, G.; Efron, B.; Butcher, P.D.; Nathan, C.; Schoolnik, G.K. Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages: Insights into the Phagosomal Environment. J. Exp. Med., 2003, 198(5), 693-704.
[123]
Dubnau, E.; Chan, J.; Raynaud, C.; Mohan, V.P.; Laneelle, M.A.; Yu, K.; Quemard, A.; Smith, I.; Daffe, M. Oxygenated mycolic acids are necessary for virulence of Mycobacterium tuberculosis in mice. Mol. Microbiol., 2000, 36(3), 630-637.
[124]
Corrales, R.M.; Molle, V.; Leiba, J.; Mourey, L.; de Chastellier, C.; Kremer, L. Phosphorylation of mycobacterial PcaA inhibits mycolic acid cyclopropanation. J. Biol. Chem., 2012, 287(31), 26187-26199.
[125]
Jang, J.; Stella, A.; Boudou, F.; Levillain, F.; Darthuy, E.; Vaubourgeix, J.; Wang, C.; Bardou, F.; Puzo, G.; Gilleron, M.; Burlet-Schiltz, O.; Monsarrat, B.; Brodin, P.; Gicquel, B.; Neyrolles, O. Functional characterization of the Mycobacterium tuberculosis serine/threonine kinase PknJ. Microbiology (Reading, U.K.), 2010, 156(6), 1619-1631.
[126]
Khan, S.; Nagarajan, S.N.; Parikh, A.; Samantaray, S.; Singh, A.; Kumar, D.; Roy, R.P.; Bhatt, A.; Nandicoori, V.K. Phosphorylation of enoyl-acyl carrier protein reductase InhA impacts mycobacterial growth and survival. J. Biol. Chem., 2010, 285(48), 37860-37871.
[127]
Kumar, P.; Kumar, D.; Parikh, A.; Rananaware, D.; Gupta, M.; Singh, Y.; Nandicoori, V.K. The Mycobacterium tuberculosis protein kinase K modulates activation of transcription from the promoter of mycobacterial monooxygenase operon through phosphorylation of the transcriptional regulator VirS. J. Biol. Chem., 2009, 284(17), 11090-11099.
[128]
Kumari, R.; Saxena, R.; Tiwari, S.; Tripathi, D.K.; Srivastava, K.K. Rv3080c regulates the rate of inhibition of mycobacteria by isoniazid through FabD. Mol. Cell. Biochem., 2013, 374(1-2), 149-155.
[129]
Molle, V.; Brown, A.K.; Besra, G.S.; Cozzone, A.J.; Kremer, L. The condensing activities of the Mycobacterium tuberculosis type II fatty acid synthase are differentially regulated by phosphorylation. J. Biol. Chem., 2006, 281(40), 30094-30103.
[130]
Molle, V.; Gulten, G.; Vilcheze, C.; Veyron-Churlet, R.; Zanella-Cleon, I.; Sacchettini, J.C.; Jacobs, W.R., Jr; Kremer, L. Phosphorylation of InhA inhibits mycolic acid biosynthesis and growth of Mycobacterium tuberculosis. Mol. Microbiol., 2010, 78(6), 1591-1605.
[131]
Molle, V.; Kremer, L.; Girard-Blanc, C.; Besra, G.S.; Cozzone, A.J.; Prost, J.F. An FHA phosphoprotein recognition domain mediates protein EmbR phosphorylation by PknH, a Ser/Thr protein kinase from Mycobacterium tuberculosis. Biochemistry, 2003, 42(51), 15300-15309.
[132]
Sharma, K.; Gupta, M.; Pathak, M.; Gupta, N.; Koul, A.; Sarangi, S.; Baweja, R.; Singh, Y. Transcriptional control of the mycobacterial embCAB operon by PknH through a regulatory protein, EmbR, in vivo. J. Bacteriol., 2006, 188(8), 2936-2944.
[133]
Singh, A.; Gupta, R.; Vishwakarma, R.A.; Narayanan, P.R.; Paramasivan, C.N.; Ramanathan, V.D.; Tyagi, A.K. Requirement of the mymA operon for appropriate cell wall ultrastructure and persistence of Mycobacterium tuberculosis in the spleens of guinea pigs. J. Bacteriol., 2005, 187(12), 4173-4186.
[134]
Slama, N.; Leiba, J.; Eynard, N.; Daffe, M.; Kremer, L.; Quemard, A.; Molle, V. Negative regulation by Ser/Thr phosphorylation of HadAB and HadBC dehydratases from Mycobacterium tuberculosis type II fatty acid synthase system. Biochem. Biophys. Res. Commun., 2011, 412(3), 401-406.
[135]
Veyron-Churlet, R.; Molle, V.; Taylor, R.C.; Brown, A.K.; Besra, G.S.; Zanella-Cleon, I.; Futterer, K.; Kremer, L. The Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III activity is inhibited by phosphorylation on a single threonine residue. J. Biol. Chem., 2009, 284(10), 6414-6424.
[136]
Veyron-Churlet, R.; Zanella-Cleon, I.; Cohen-Gonsaud, M.; Molle, V.; Kremer, L. Phosphorylation of the Mycobacterium tuberculosis β-Ketoacyl-Acyl Carrier Protein Reductase MabA Regulates Mycolic Acid Biosynthesis. J. Biol. Chem., 2010, 285(17), 12714-12725.
[137]
Sinha, I.; Boon, C.; Dick, T. Apparent growth phase-dependent phosphorylation of malonyl coenzyme A: Acyl carrier protein transacylase (MCAT), a major fatty acid synthase II component in Mycobacterium bovis BCG. FEMS Microbiol. Lett., 2003, 227(1), 141-147.
[138]
Vilcheze, C.; Molle, V.; Carrere-Kremer, S.; Leiba, J.; Mourey, L.; Shenai, S.; Baronian, G.; Tufariello, J.; Hartman, T.; Veyron-Churlet, R.; Trivelli, X.; Tiwari, S.; Weinrick, B.; Alland, D.; Guerardel, Y.; Jacobs, W.R., Jr; Kremer, L. Phosphorylation of KasB regulates virulence and acid-fastness in Mycobacterium tuberculosis. PLoS Pathog., 2014, 10(5), e1004115.
[139]
Dasgupta, A.; Datta, P.; Kundu, M.; Basu, J. The serine/threonine kinase PknB of Mycobacterium tuberculosis phosphorylates PBPA, a penicillin-binding protein required for cell division. Microbiology, 2006, 152(Pt 2), 493-504.
[140]
Gupta, M.; Sajid, A.; Arora, G.; Tandon, V.; Singh, Y. Forkhead-associated domain-containing protein Rv0019c and polyketide-associated protein PapA5, from substrates of serine/threonine protein kinase PknB to interacting proteins of Mycobacterium tuberculosis. J. Biol. Chem., 2009, 284(50), 34723-34734.
[141]
Kang, C.M.; Abbott, D.W.; Park, S.T.; Dascher, C.C.; Cantley, L.C.; Husson, R.N. The Mycobacterium tuberculosis serine/threonine kinases PknA and PknB: Substrate identification and regulation of cell shape. Genes Dev., 2005, 19(14), 1692-1704.
[142]
Kang, C.M.; Nyayapathy, S.; Lee, J.Y.; Suh, J.W.; Husson, R.N. Wag31, a homologue of the cell division protein DivIVA, regulates growth, morphology and polar cell wall synthesis in mycobacteria. Microbiology, 2008, 154(Pt 3), 725-735.
[143]
Parikh, A.; Verma, S.K.; Khan, S.; Prakash, B.; Nandicoori, V.K. PknB-mediated phosphorylation of a novel substrate, N-acetylglucosamine-1-phosphate uridyltransferase, modulates its acetyltransferase activity. J. Mol. Biol., 2009, 386(2), 451-464.
[144]
Thakur, M.; Chakraborti, P.K. GTPase activity of mycobacterial FtsZ is impaired due to its transphosphorylation by the eukaryotic-type Ser/Thr kinase, PknA. J. Biol. Chem., 2006, 281(52), 40107-40113.
[145]
Thakur, M.; Chakraborti, P.K. Ability of PknA, a mycobacterial eukaryotic-type serine/threonine kinase, to transphosphorylate MurD, a ligase involved in the process of peptidoglycan biosynthesis. Biochem. J., 2008, 415(1), 27-33.
[146]
Kumari, R.; Singh, S.K.; Singh, D.K.; Singh, P.K.; Chaurasiya, S.K.; Srivastava, K.K. Functional characterization delineates that a Mycobacterium tuberculosis specific protein kinase (Rv3080c) is responsible for the growth, phagocytosis and intracellular survival of avirulent mycobacteria. Mol. Cell. Biochem., 2012, 369(1-2), 67-74.
[147]
Malhotra, V.; Arteaga-Cortes, L.T.; Clay, G.; Clark-Curtiss, J.E. Mycobacterium tuberculosis protein kinase K confers survival advantage during early infection in mice and regulates growth in culture and during persistent infection: Implications for immune modulation. Microbiology, 2010, 156(Pt 9), 2829-2841.
[148]
Brown, A.K.; Bhatt, A.; Singh, A.; Saparia, E.; Evans, A.F.; Besra, G.S. Identification of the dehydratase component of the mycobacterial mycolic acid-synthesizing fatty acid synthase-II complex. Microbiology, 2007, 153(Pt 12), 4166-4173.
[149]
Vilcheze, C.; Morbidoni, H.R.; Weisbrod, T.R.; Iwamoto, H.; Kuo, M.; Sacchettini, J.C.; Jacobs, W.R., Jr Inactivation of the inhA-encoded fatty acid synthase II (FASII) enoyl-acyl carrier protein reductase induces accumulation of the FASI end products and cell lysis of Mycobacterium smegmatis. J. Bacteriol., 2000, 182(14), 4059-4067.
[150]
North, E.J.; Jackson, M.; Lee, R.E. New approaches to target the mycolic acid biosynthesis pathway for the development of tuberculosis therapeutics. Curr. Pharm. Des., 2014, 20(27), 4357-4378.
[151]
Vilcheze, C.; Jacobs, W.R., Jr The mechanism of isoniazid killing: clarity through the scope of genetics. Annu. Rev. Microbiol., 2007, 61, 35-50.
[152]
Banerjee, A.; Sugantino, M.; Sacchettini, J.C.; Jacobs, W.R., Jr The mabA gene from the inhA operon of Mycobacterium tuberculosis encodes a 3-ketoacyl reductase that fails to confer isoniazid resistance. Microbiology, 1998, 144(Pt 10), 2697-2704.
[153]
Chaba, R.; Raje, M.; Chakraborti, P.K. Evidence that a eukaryotic-type serine/threonine protein kinase from Mycobacterium tuberculosis regulates morphological changes associated with cell division. Eur. J. Biochem., 2002, 269(4), 1078-1085.
[154]
Nagarajan, S.N.; Upadhyay, S.; Chawla, Y.; Khan, S.; Naz, S.; Subramanian, J.; Gandotra, S.; Nandicoori, V.K. Protein kinase A (PknA) of Mycobacterium tuberculosis is independently activated and is critical for growth in vitro and survival of the pathogen in the host. J. Biol. Chem., 2015, 290(15), 9626-9645.
[155]
Glickman, M.S.; Cox, J.S.; Jacobs, W.R., Jr A novel mycolic acid cyclopropane synthetase is required for cording, persistence, and virulence of Mycobacterium tuberculosis. Mol. Cell, 2000, 5(4), 717-727.
[156]
de Chastellier, C. The many niches and strategies used by pathogenic mycobacteria for survival within host macrophages. Immunobiology, 2009, 214(7), 526-542.
[157]
de Chastellier, C.; Forquet, F.; Gordon, A.; Thilo, L. Mycobacterium requires an all-around closely apposing phagosome membrane to maintain the maturation block and this apposition is re-established when it rescues itself from phagolysosomes. Cell. Microbiol., 2009, 11(8), 1190-1207.
[158]
Singh, A.; Jain, S.; Gupta, S.; Das, T.; Tyagi, A.K. mymA operon of Mycobacterium tuberculosis: Its regulation and importance in the cell envelope. FEMS Microbiol. Lett., 2003, 227(1), 53-63.
[159]
Bialy, L.; Waldmann, H. Inhibitors of protein tyrosine phosphatases: next-generation drugs? Angew. Chem. Int. Ed. Engl., 2005, 44(25), 3814-3839.
[160]
Lapenna, S.; Giordano, A. Cell cycle kinases as therapeutic targets for cancer. Nat. Rev. Drug Discov., 2009, 8(7), 547-566.
[161]
Tabernero, L.; Aricescu, A.R.; Jones, E.Y.; Szedlacsek, S.E. Protein tyrosine phosphatases: Structure-function relationships. FEBS J., 2008, 275(5), 867-882.
[162]
Vintonyak, V.V.; Antonchick, A.P.; Rauh, D.; Waldmann, H. The therapeutic potential of phosphatase inhibitors. Curr. Opin. Chem. Biol., 2009, 13(3), 272-283.
[163]
Zhang, J.; Yang, P.L.; Gray, N.S. Targeting cancer with small molecule kinase inhibitors. Nat. Rev. Cancer, 2009, 9(1), 28-39.
[164]
Zhang, Z.Y. Protein tyrosine phosphatases: Prospects for therapeutics. Curr. Opin. Chem. Biol., 2001, 5(4), 416-423.
[165]
Wu, P.; Nielsen, T.E.; Clausen, M.H. Small-molecule kinase inhibitors: An analysis of FDA-approved drugs. Drug Discov. Today, 2016, 21(1), 5-10.
[166]
Wong, D.; Chao, J.D.; Av-Gay, Y. Mycobacterium tuberculosis-secreted phosphatases: From pathogenesis to targets for TB drug development. Trends Microbiol., 2013, 21(2), 100-109.
[167]
Sassetti, C.M.; Boyd, D.H.; Rubin, E.J. Genes required for mycobacterial growth defined by high density mutagenesis. Mol. Microbiol., 2003, 48(1), 77-84.
[168]
Cowley, S.; Ko, M.; Pick, N.; Chow, R.; Downing, K.J.; Gordhan, B.G.; Betts, J.C.; Mizrahi, V.; Smith, D.A.; Stokes, R.W.; Av-Gay, Y. The Mycobacterium tuberculosis protein serine/threonine kinase PknG is linked to cellular glutamate/glutamine levels and is important for growth in vivo. Mol. Microbiol., 2004, 52(6), 1691-1702.
[169]
Chawla, Y.; Upadhyay, S.; Khan, S.; Nagarajan, S.N.; Forti, F.; Nandicoori, V.K. Protein kinase B (PknB) of Mycobacterium tuberculosis is essential for growth of the pathogen in vitro as well as for survival within the host. J. Biol. Chem., 2014, 289(20), 13858-13875.
[170]
Papavinasasundaram, K.G.; Chan, B.; Chung, J.H.; Colston, M.J.; Davis, E.O.; Av-Gay, Y. Deletion of the Mycobacterium tuberculosis pknH gene confers a higher bacillary load during the chronic phase of infection in BALB/c mice. J. Bacteriol., 2005, 187(16), 5751-5760.
[171]
Walburger, A.; Koul, A.; Ferrari, G.; Nguyen, L.; Prescianotto-Baschong, C.; Huygen, K.; Klebl, B.; Thompson, C.; Bacher, G.; Pieters, J. Protein kinase G from pathogenic mycobacteria promotes survival within macrophages. Science, 2004, 304(5678), 1800-1804.
[172]
Fernandez, P.; Saint-Joanis, B.; Barilone, N.; Jackson, M.; Gicquel, B.; Cole, S.T.; Alzari, P.M. The Ser/Thr protein kinase PknB is essential for sustaining mycobacterial growth. J. Bacteriol., 2006, 188(22), 7778-7784.
[173]
Zhang, N.; Torrelles, J.B.; McNeil, M.R.; Escuyer, V.E.; Khoo, K.H.; Brennan, P.J.; Chatterjee, D. The Emb proteins of mycobacteria direct arabinosylation of lipoarabinomannan and arabinogalactan via an N-terminal recognition region and a C-terminal synthetic region. Mol. Microbiol., 2003, 50(1), 69-76.
[174]
Briken, V.; Porcelli, S.A.; Besra, G.S.; Kremer, L. Mycobacterial lipoarabinomannan and related lipoglycans: From biogenesis to modulation of the immune response. Mol. Microbiol., 2004, 53(2), 391-403.
[175]
Escuyer, V.E.; Lety, M.A.; Torrelles, J.B.; Khoo, K.H.; Tang, J.B.; Rithner, C.D.; Frehel, C.; McNeil, M.R.; Brennan, P.J.; Chatterjee, D. The role of the embA and embB gene products in the biosynthesis of the terminal hexaarabinofuranosyl motif of Mycobacterium smegmatis arabinogalactan. J. Biol. Chem., 2001, 276(52), 48854-48862.
[176]
Deol, P.; Vohra, R.; Saini, A.K.; Singh, A.; Chandra, H.; Chopra, P.; Das, T.K.; Tyagi, A.K.; Singh, Y. Role of Mycobacterium tuberculosis Ser/Thr kinase PknF: Implications in glucose transport and cell division. J. Bacteriol., 2005, 187(10), 3415-3420.
[177]
Gopalaswamy, R.; Narayanan, S.; Chen, B.; Jacobs, W.R.; Av-Gay, Y. The serine/threonine protein kinase PknI controls the growth of Mycobacterium tuberculosis upon infection. FEMS Microbiol. Lett., 2009, 295(1), 23-29.
[178]
Arora, G.; Sajid, A.; Gupta, M.; Bhaduri, A.; Kumar, P.; Basu-Modak, S.; Singh, Y. Understanding the role of PknJ in Mycobacterium tuberculosis: Biochemical characterization and identification of novel substrate pyruvate kinase A. PLoS One, 2010, 5(5), e10772.
[179]
Ortega, C.; Liao, R.; Anderson, L.N.; Rustad, T.; Ollodart, A.R.; Wright, A.T.; Sherman, D.R.; Grundner, C. Mycobacterium tuberculosis Ser/Thr protein kinase B mediates an oxygen-dependent replication switch. PLoS Biol., 2014, 12(1), e1001746.
[180]
Scherr, N.; Honnappa, S.; Kunz, G.; Mueller, P.; Jayachandran, R.; Winkler, F.; Pieters, J.; Steinmetz, M.O. Structural basis for the specific inhibition of protein kinase G, a virulence factor of Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA, 2007, 104(29), 12151-12156.
[181]
O’Hare, H.M.; Duran, R.; Cervenansky, C.; Bellinzoni, M.; Wehenkel, A.M.; Pritsch, O.; Obal, G.; Baumgartner, J.; Vialaret, J.; Johnsson, K.; Alzari, P.M. Regulation of glutamate metabolism by protein kinases in mycobacteria. Mol. Microbiol., 2008, 70(6), 1408-1423.
[182]
Villarino, A.; Duran, R.; Wehenkel, A.; Fernandez, P.; England, P.; Brodin, P.; Cole, S.T.; Zimny-Arndt, U.; Jungblut, P.R.; Cervenansky, C.; Alzari, P.M. Proteomic identification of M. tuberculosis protein kinase substrates: PknB recruits GarA, a FHA domain-containing protein, through activation loop-mediated interactions. J. Mol. Biol., 2005, 350(5), 953-963.
[183]
Magnet, S.; Hartkoorn, R.C.; Szekely, R.; Pato, J.; Triccas, J.A.; Schneider, P.; Szantai-Kis, C.; Orfi, L.; Chambon, M.; Banfi, D.; Bueno, M.; Turcatti, G.; Keri, G.; Cole, S.T. Leads for antitubercular compounds from kinase inhibitor library screens. Tuberculosis (Edinb.), 2010, 90(6), 354-360.
[184]
Chapman, T.M.; Bouloc, N.; Buxton, R.S.; Chugh, J.; Lougheed, K.E.; Osborne, S.A.; Saxty, B.; Smerdon, S.J.; Taylor, D.L.; Whalley, D. Substituted aminopyrimidine protein kinase B (PknB) inhibitors show activity against Mycobacterium tuberculosis. Bioorg. Med. Chem. Lett., 2012, 22(9), 3349-3353.
[185]
Lougheed, K.E.; Osborne, S.A.; Saxty, B.; Whalley, D.; Chapman, T.; Bouloc, N.; Chugh, J.; Nott, T.J.; Patel, D.; Spivey, V.L.; Kettleborough, C.A.; Bryans, J.S.; Taylor, D.L.; Smerdon, S.J.; Buxton, R.S. Effective inhibitors of the essential kinase PknB and their potential as anti-mycobacterial agents. Tuberculosis (Edinb.), 2011, 91(4), 277-286.
[186]
Szekely, R.; Waczek, F.; Szabadkai, I.; Nemeth, G.; Hegymegi-Barakonyi, B.; Eros, D.; Szokol, B.; Pato, J.; Hafenbradl, D.; Satchell, J.; Saint-Joanis, B.; Cole, S.T.; Orfi, L.; Klebl, B.M.; Keri, G. A novel drug discovery concept for tuberculosis: Inhibition of bacterial and host cell signalling. Immunol. Lett., 2008, 116(2), 225-231.
[187]
Chen, D.; Ma, S.; He, L.; Yuan, P.; She, Z.; Lu, Y. Sclerotiorin inhibits protein kinase G from Mycobacterium tuberculosis and impairs mycobacterial growth in macrophages. Tuberculosis (Edinb.), 2017, 103, 37-43.
[188]
Anand, N.; Singh, P.; Sharma, A.; Tiwari, S.; Singh, V.; Singh, D.K.; Srivastava, K.K.; Singh, B.N.; Tripathi, R.P. Synthesis and evaluation of small libraries of triazolylmethoxy chalcones, flavanones and 2-aminopyrimidines as inhibitors of mycobacterial FAS-II and PknG. Bioorg. Med. Chem., 2012, 20(17), 5150-5163.
[189]
Hegymegi-Barakonyi, B.; Szekely, R.; Varga, Z.; Kiss, R.; Borbely, G.; Nemeth, G.; Banhegyi, P.; Pato, J.; Greff, Z.; Horvath, Z.; Meszaros, G.; Marosfalvi, J.; Eros, D.; Szantai-Kis, C.; Breza, N.; Garavaglia, S.; Perozzi, S.; Rizzi, M.; Hafenbradl, D.; Ko, M.; Av-Gay, Y.; Klebl, B.M.; Orfi, L.; Keri, G. Signalling inhibitors against Mycobacterium tuberculosis--early days of a new therapeutic concept in tuberculosis. Curr. Med. Chem., 2008, 15(26), 2760-2770.
[190]
Sipos, A.; Pato, J.; Szekely, R.; Hartkoorn, R.C.; Kekesi, L.; Orfi, L.; Szantai-Kis, C.; Mikusova, K.; Svetlikova, Z.; Kordulakova, J.; Nagaraja, V.; Godbole, A.A.; Bush, N.; Collin, F.; Maxwell, A.; Cole, S.T.; Keri, G. Lead selection and characterization of antitubercular compounds using the Nested Chemical Library. Tuberculosis (Edinb.), 2015, 95(Suppl. 1), S200-S206.
[191]
Xu, J.; Wang, J.X.; Zhou, J.M.; Xu, C.L.; Huang, B.; Xing, Y.; Wang, B.; Luo, R.; Wang, Y.C.; You, X.F.; Lu, Y.; Yu, L.Y. A novel protein kinase inhibitor IMB-YH-8 with anti-tuberculosis activity. Sci. Rep., 2017, 7(1), 5093.
[192]
Wang, T.; Bemis, G.; Hanzelka, B.; Zuccola, H.; Wynn, M.; Moody, C.S.; Green, J.; Locher, C.; Liu, A.; Gao, H.; Xu, Y.; Wang, S.; Wang, J.; Bennani, Y.L.; Thomson, J.A.; Muh, U. Mtb PKNA/PKNB dual inhibition provides selectivity advantages for inhibitor design to minimize host kinase interactions. ACS Med. Chem. Lett., 2017, 8(12), 1224-1229.
[193]
Grundner, C.; Ng, H.L.; Alber, T. Mycobacterium tuberculosis protein tyrosine phosphatase PtpB structure reveals a diverged fold and a buried active site. Structure, 2005, 13(11), 1625-1634.
[194]
Chiaradia, L.D.; Martins, P.G.; Cordeiro, M.N.; Guido, R.V.; Ecco, G.; Andricopulo, A.D.; Yunes, R.A.; Vernal, J.; Nunes, R.J.; Terenzi, H. Synthesis, biological evaluation, and molecular modeling of chalcone derivatives as potent inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatases (PtpA and PtpB). J. Med. Chem., 2012, 55(1), 390-402.
[195]
Chiaradia, L.D.; Mascarello, A.; Purificacao, M.; Vernal, J.; Cordeiro, M.N.; Zenteno, M.E.; Villarino, A.; Nunes, R.J.; Yunes, R.A.; Terenzi, H. Synthetic chalcones as efficient inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase PtpA. Bioorg. Med. Chem. Lett., 2008, 18(23), 6227-6230.
[196]
Correa, I.R., Jr; Noren-Muller, A.; Ambrosi, H.D.; Jakupovic, S.; Saxena, K.; Schwalbe, H.; Kaiser, M.; Waldmann, H. Identification of inhibitors for mycobacterial protein tyrosine phosphatase B (MptpB) by biology-oriented synthesis (BIOS). Chem. Asian J., 2007, 2(9), 1109-1126.
[197]
Grundner, C.; Perrin, D.; Hooft van Huijsduijnen, R.; Swinnen, D.; Gonzalez, J.; Gee, C.L.; Wells, T.N.; Alber, T. Structural basis for selective inhibition of Mycobacterium tuberculosis protein tyrosine phosphatase PtpB. Structure, 2007, 15(4), 499-509.
[198]
Manger, M.; Scheck, M.; Prinz, H.; von Kries, J.P.; Langer, T.; Saxena, K.; Schwalbe, H.; Furstner, A.; Rademann, J.; Waldmann, H. Discovery of Mycobacterium tuberculosis protein tyrosine phosphatase A (MptpA) inhibitors based on natural products and a fragment-based approach. Chembiochem, 2005, 6(10), 1749-1753.
[199]
Noren-Muller, A.; Reis-Correa, I., Jr; Prinz, H.; Rosenbaum, C.; Saxena, K.; Schwalbe, H.J.; Vestweber, D.; Cagna, G.; Schunk, S.; Schwarz, O.; Schiewe, H.; Waldmann, H. Discovery of protein phosphatase inhibitor classes by biology-oriented synthesis. Proc. Natl. Acad. Sci. USA, 2006, 103(28), 10606-10611.
[200]
Noren-Muller, A.; Wilk, W.; Saxena, K.; Schwalbe, H.; Kaiser, M.; Waldmann, H. Discovery of a new class of inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase B by biology-oriented synthesis. Angew. Chem. Int. Ed. Engl., 2008, 47(32), 5973-5977.
[201]
Rawls, K.A.; Lang, P.T.; Takeuchi, J.; Imamura, S.; Baguley, T.D.; Grundner, C.; Alber, T.; Ellman, J.A. Fragment-based discovery of selective inhibitors of the Mycobacterium tuberculosis protein tyrosine phosphatase PtpA. Bioorg. Med. Chem. Lett., 2009, 19(24), 6851-6854.
[202]
Soellner, M.B.; Rawls, K.A.; Grundner, C.; Alber, T.; Ellman, J.A. Fragment-based substrate activity screening method for the identification of potent inhibitors of the Mycobacterium tuberculosis phosphatase PtpB. J. Am. Chem. Soc., 2007, 129(31), 9613-9615.
[203]
Tan, L.P.; Wu, H.; Yang, P.Y.; Kalesh, K.A.; Zhang, X.; Hu, M.; Srinivasan, R.; Yao, S.Q. High-throughput discovery of Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) inhibitors using click chemistry. Org. Lett., 2009, 11(22), 5102-5105.
[204]
Vintonyak, V.V.; Warburg, K.; Kruse, H.; Grimme, S.; Hubel, K.; Rauh, D.; Waldmann, H. Identification of thiazolidinones spiro-fused to indolin-2-ones as potent and selective inhibitors of the Mycobacterium tuberculosis protein tyrosine phosphatase B. Angew. Chem. Int. Ed. Engl., 2010, 49(34), 5902-5905.
[205]
Zeng, L.F.; Xu, J.; He, Y.; He, R.; Wu, L.; Gunawan, A.M.; Zhang, Z.Y. A facile hydroxyindole carboxylic acid based focused library approach for potent and selective inhibitors of Mycobacterium protein tyrosine phosphatase B. ChemMedChem, 2013, 8(6), 904-908.
[206]
Mascarello, A.; Chiaradia, L.D.; Vernal, J.; Villarino, A.; Guido, R.V.; Perizzolo, P.; Poirier, V.; Wong, D.; Martins, P.G.; Nunes, R.J.; Yunes, R.A.; Andricopulo, A.D.; Av-Gay, Y.; Terenzi, H. Inhibition of Mycobacterium tuberculosis tyrosine phosphatase PtpA by synthetic chalcones: kinetics, molecular modeling, toxicity and effect on growth. Bioorg. Med. Chem., 2010, 18(11), 3783-3789.
[207]
Chen, L.; Zhou, B.; Zhang, S.; Wu, L.; Wang, Y.; Franzblau, S.G.; Zhang, Z.Y. Identification and characterization of novel inhibitors of mPTPB, an essential virulent phosphatase from Mycobacterium tuberculosis. ACS Med. Chem. Lett., 2010, 1(7), 355-359.
[208]
Beresford, N.J.; Mulhearn, D.; Szczepankiewicz, B.; Liu, G.; Johnson, M.E.; Fordham-Skelton, A.; Abad-Zapatero, C.; Cavet, J.S.; Tabernero, L. Inhibition of MptpB phosphatase from Mycobacterium tuberculosis impairs mycobacterial survival in macrophages. J. Antimicrob. Chemother., 2009, 63(5), 928-936.
[209]
Mascarello, A.; Orbem Menegatti, A.C.; Calcaterra, A.; Martins, P.G.A.; Chiaradia-Delatorre, L.D.; D’Acquarica, I.; Ferrari, F.; Pau, V.; Sanna, A.; De Logu, A.; Botta, M.; Botta, B.; Terenzi, H.; Mori, M. Naturally occurring Diels-Alder-type adducts from Morus nigra as potent inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase B. Eur. J. Med. Chem., 2018, 144, 277-288.
[210]
Dutta, N.K.; He, R.; Pinn, M.L.; He, Y.; Burrows, F.; Zhang, Z.Y.; Karakousis, P.C. Mycobacterial Protein Tyrosine Phosphatases A and B Inhibitors Augment the Bactericidal Activity of the Standard Anti-tuberculosis Regimen. ACS Infect. Dis., 2016, 2(3), 231-239.
[211]
Buttini, F. Colombo: G. In Drug Delivry Systems for Tuberculosis Prevention and Treatment, 2016.
[212]
Praphakar, R.A.; Shakila, H.; Azger Dusthackeer, V.N.; Munusamy, M.A.; Kumar, S.; Rajan, M. A mannose-conjugated multi-layered polymeric nanocarrier system for controlled and targeted release on alveolar macrophages. Polym. Chem., 2018, 9(5), 656-667.
[213]
Banerjee, S.; Roy, S.; Nath Bhaumik, K.; Kshetrapal, P.; Pillai, J. Comparative study of oral lipid nanoparticle formulations (LNFs) for chemical stabilization of antitubercular drugs: Physicochemical and cellular evaluation. Artif. Cells Nanomed. Biotechnol., 2018, 1-19.
[214]
Oliveira, P.M.; Matos, B.N.; Pereira, P.A.; Gratieri, T.; Faccioli, L.H.; Cunha-Filho, M.S.; Gelfuso, G.M. Microparticles prepared with 50–190 kDa chitosan as promising non-toxic carriers for pulmonary delivery of isoniazid. Carbohydr. Polym., 2017, 174, 421-431.
[215]
Li, D.; Li, L.; Ma, Y.; Zhuang, Y.; Li, D.; Shen, H.; Wang, X.; Yang, F.; Ma, Y.; Wu, D. Dopamine-assisted fixation of drug-loaded polymeric multilayers to osteoarticular implants for tuberculosis therapy. Biomaterials Bci., 2017, 5(4), 730-740.
[216]
Bhardwaj, A.; Mehta, S.; Yadav, S.; Singh, S.K.; Grobler, A.; Goyal, A.K.; Mehta, A. Pulmonary delivery of antitubercular drugs using spray-dried lipid–polymer hybrid nanoparticles. Artif. Cells Nanomed. Biotechnol., 2016, 44(6), 1544-1555.
[217]
Garg, T.; Goyal, A.K.; Rath, G.; Murthy, R. Spray-dried particles as pulmonary delivery system of anti-tubercular drugs: Design, optimization, in vitro and in vivo evaluation. Pharm. Develop. Technol., 2016, 21(8), 951-960.
[218]
Alves, A.D.; Cavaco, J.S.; Guerreiro, F.; Lourenço, J.P.; Rosa da Costa, A.M.; Grenha, A. Inhalable antitubercular therapy mediated by locust bean gum microparticles. Molecules, 2016, 21(6), 702.
[219]
Hussain, A.; Singh, S.K.; Singh, N.; Verma, P.R.P. In vitro–in vivo–in silico simulation studies of anti-tubercular drugs doped with a self nanoemulsifying drug delivery system. RSC Adv, 2016, 6(95), 93147-93161.
[220]
Goyal, A.K.; Garg, T.; Rath, G.; Gupta, U.D.; Gupta, P. Development and characterization of nanoembedded microparticles for pulmonary delivery of antitubercular drugs against experimental tuberculosis. Mol. Pharm., 2015, 12(11), 3839-3850.
[221]
Saifullah, B.; Maitra, A.; Chrzastek, A.; Naeemullah, B.; Fakurazi, S.; Bhakta, S.; Hussein, M.Z. Nano-formulation of Ethambutol with multifunctional Graphene Oxide and magnetic nanoparticles retains Its anti-tubercular activity with prospects of improving chemotherapeutic efficacy. Molecules, 2017, 22(10), 1697.
[222]
El-Ridy, M.S.; Yehia, S.A.; Kassem, M.A-E-M.; Mostafa, D.M.; Nasr, E.A.; Asfour, M.H. Niosomal encapsulation of ethambutol hydrochloride for increasing its efficacy and safety. Drug Deliv., 2015, 22(1), 21-36.
[223]
Ahmad, M.I.; Nakpheng, T.; Srichana, T. The safety of ethambutol dihydrochloride dry powder formulations containing chitosan for the possibility of treating lung tuberculosis. Inhal. Toxicol., 2014, 26(14), 908-917.
[224]
Costa-Gouveia, J.; Pancani, E.; Jouny, S.; Machelart, A.; Delorme, V.; Salzano, G.; Iantomasi, R.; Piveteau, C.; Queval, C.J.; Song, O-R. Combination therapy for tuberculosis treatment: Pulmonary administration of ethionamide and booster co-loaded nanoparticles. Sci. Rep., 2017, 7(1), 5390.
[225]
Debnath, S.K.; Saisivam, S.; Omri, A. PLGA Ethionamide Nanoparticles for Pulmonary Delivery: Development and in vivo evaluation of dry powder inhaler. J. Pharm. Biomed. Anal., 2017, 145, 854-859.
[226]
Kumar, G.; Malhotra, S.; Shafiq, N.; Pandhi, P.; Khuller, G.K.; Sharma, S. In vitro physicochemical characterization and short term in vivo tolerability study of ethionamide loaded PLGA nanoparticles: potentially effective agent for multidrug resistant tuberculosis. J. Microencapsul., 2011, 28(8), 717-728.
[227]
Matsunaga, I.; Naka, T.; Talekar, R.S.; McConnell, M.J.; Katoh, K.; Nakao, H.; Otsuka, A.; Behar, S.M.; Yano, I.; Moody, D.B.; Sugita, M. Mycolyltransferase-mediated glycolipid exchange in Mycobacteria. J. Biol. Chem., 2008, 283(43), 28835-28841.
[228]
De Smet, K.A.; Weston, A.; Brown, I.N.; Young, D.B.; Robertson, B.D. Three pathways for trehalose biosynthesis in mycobacteria. Microbiology, 2000, 146(Pt 1), 199-208.
[229]
Woodruff, P.J.; Carlson, B.L.; Siridechadilok, B.; Pratt, M.R.; Senaratne, R.H.; Mougous, J.D.; Riley, L.W.; Williams, S.J.; Bertozzi, C.R. Trehalose is required for growth of Mycobacterium smegmatis. J. Biol. Chem., 2004, 279(28), 28835-28843.
[230]
Perez, J.; Garcia, R.; Bach, H.; de Waard, J.H.; Jacobs, W.R., Jr; Av-Gay, Y.; Bubis, J.; Takiff, H.E. Mycobacterium tuberculosis transporter MmpL7 is a potential substrate for kinase PknD. Biochem. Biophys. Res. Commun., 2006, 348(1), 6-12.
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