<< doi: 10.1128/AAC.01462-13, Hoagland, D. T., Liu, J., Lee, R. B., and Lee, R. E. (2016). >> Belcher Dufrisne M, Jorge CD, Timóteo CG, Petrou VI, Ashraf KU, Banerjee S, Clarke OB, Santos H, Mancia F. J Mol Biol. >> 167 0 obj 323 0 R 324 0 R] << Identification of novel imidazo[1,2-a]pyridine inhibitors targeting M. tuberculosis QcrB. >>

/Contents [309 0 R 310 0 R 311 0 R] Despite several appealing properties (rapid killing, low immunogenicity, uptake by macrophages, immunomodulatory properties) which render AMPs highly attractive as antimycobacterial candidates, their clinical advancement has been hampered by stability and pharmacokinetic issues arising from their peptidic character (Arranz-Trullén et al., 2017).

>> By continuing you agree to the use of cookies. doi: 10.1016/j.tube.2013.09.003, Gupta, S., Cohen, K. A., Winglee, K., Maiga, M., Diarra, B., and Bishai, W. R. (2014).
The final step involves insertion of the AMP in the IM bilayer and the ensuing loss of membrane permeability. Mycolic acids: structures, biosynthesis, and beyond. /D [30 0 R /FitR 291 243 534 217] For example, penetratin did not induce pore formation in bacterial membranes in spite of its cationic amphipathic character (Huang and Charron, 2017) while buforin II penetrated the cytoplasmic membrane and accumulated within the cytosol, without incurring significant damage to the membrane (Park et al., 2000).

/D [33 0 R /FitR 307 567 550 541] Science 1993; 261(5127): 1454-7. In keeping with its cationic amphiphilic character, Ub2 disrupted the membrane integrity of mycobacteria. 274 0 obj Influence of iron deprivation on virulence traits of mycobacteria. << Agents Chemother. ACS Med. >> >> becoming ineffective, particularly due to emergence of drug resistance in MTB. 92 0 obj endobj There are also differing opinions about the nature of the IM. (2017). This was attributed to the higher lipophilicities of the shortlisted compounds (average log P of 4) which exceeded that of current TB drugs (average log P of 1). /D [31 0 R /FitR 307 504 550 478] 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. /Annots [478 0 R 479 0 R 480 0 R 481 0 R 482 0 R 483 0 R 484 0 R 485 0 R 486 0 R 487 0 R doi: 10.1038/nrmicro2549, Li, M., Nyantakyi, S. A., Gopal, P., Aziz, D. B., Dick, T., and Go, M. L. (2017). endobj Lin, S., Koh, J. J., Aung, T. T., Sin, W. L. W., Lim, F., Wang, L., et al.

(2017). << /CropBox [0 0 595.276 841.89] Received: 03 April 2018; Accepted: 28 June 2018; Published: 19 July 2018.

Further extraction with solvents more polar than CHCl3-CH3OH (2:1), namely CHCl3-CH3OH-H2O (10:10:3) (33) and “E-soak” (water-ethanol-diethyl ether-pyridine-ammonium hydroxide at 5:15:5:1:0.017) (2), removed the C50-P-P-GlcNAc-Rha-based galactan polymers, which were resolved by SDS-PAGE and visualized by autoradiography (Fig.

endobj /Rotate 0 Like AM-0016, the antimycobacterial activity of 3 involved a loss in membrane integrity. <<

endobj 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. >> Boromycin is a boron-containing polyether-macrolide antibiotic isolated from Streptomyces antibioticus. Hit and lead criteria in drug discovery for infectious diseases of the developing world. 206 0 obj 156 0 R 157 0 R 158 0 R 159 0 R 160 0 R /Prev 17 0 R

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Pal R, Hameed S, Sharma S, Fatima Z.

In this review, we examined the recent literature on different chemotypes with membrane perturbing properties, the mechanisms by which they induce membrane disruption and their potential as anti-TB agents. >> Both glycolipids GL-4 and GL-5 serve as substrates for GlfT2. Dussurget O, Rodriguez M, Smith I. << /D [19 0 R /FitR 0 842 596 0] /D [26 0 R /FitR 291 194 534 179] doi: 10.1007/BF00277157, Gengenbacher, M., and Kaufmann, S. H. (2012). The mycobacterial cell wall: structure, biosynthesis and sites of drug action. The chemistry of the lipids of the tubercle bacillus. >> 187 0 obj Interestingly, this notion has not been experimentally verified. >> 237 0 obj 498 0 R 499 0 R 500 0 R 501 0 R 502 0 R 503 0 R 504 0 R 505 0 R 506 0 R 507 0 R /D [34 0 R /FitR 47 135 289 109] The transcriptional competency of this cluster is induced by agents that increase cell envelope stress (Alland et al., 2000). Natural substrates GL-4 and GL-5 were used as acceptors of galactofuranosyl residues in the reaction catalyzed by GlfT2 expressed in the heterologous host, E. coli. >>

89 0 obj While it is apparent that the presence of the motif directs the molecule to the membrane, it does not determine how the membrane would ultimately be perturbed. Boromycin induced collapse of the mycobacterial transmembrane potential which led to leakage of cellular contents (Moreira et al., 2016). >> 238 0 obj Frontiers of Biosciences 3, 1253–1261 36, 514–532. Lanes labeled “standard” represent fractions extracted from reaction mixture containing membranes and cell wall from M. smegmatis mc2155 and UDP-[U-14C]Galp as a tracer for production of galactan intermediates (25). 108 0 obj Microbiology 1995; 141(Pt 9): 2123-30. Drug Deliv. 57 0 obj Tuberculosis (TB) poses an enduring threat to global health. In the barrel stave model, the AMPs aggregate and insert into the membrane bilayer with their hydrophobic regions pointing toward the lipid domains of the bilayer while the hydrophilic regions face inwards to form the pore. >> endobj /Contents [654 0 R 655 0 R 656 0 R] J. /D [34 0 R /FitR 47 270 289 244] endobj Microbiology 2004; 150(Pt 4): 853-64. Cell based cytotoxicity assays should be supplemented by the red blood cell hemolysis assay which provides a simple and effective means of eliminating molecules that damage mammalian membranes. 273 0 obj The Mycobacterial Cell Wall--Peptidoglycan and Arabinogalactan. << endobj /Parent 10 0 R Thus, the TPP-indoles targeted a critical membrane-based process (ETC) whereas the indolyl Mannich bases induced general membrane permeabilization. Experimental evidence presented in this paper resolves several questions raised in our previous work (22, 32). 151 0 R 152 0 R 153 0 R 154 0 R 155 0 R Arruda S, Bomfim G, Knights R, Huima-Byron T, Riley LW. /Contents [368 0 R 369 0 R 370 0 R] 38 0 obj << endobj /Parent 9 0 R endobj 275 0 obj Thus, it was with some surprise that boromycin was found to be bactericidal against mycobacteria which also possess a double membrane cell envelope. 270 0 obj /D [35 0 R /FitR 307 144 550 118] 254 0 R 255 0 R 256 0 R 257 0 R 258 0 R >> Biophys. >> endobj 259 0 R 260 0 R 261 0 R 262 0 R 263 0 R endobj Although the double membrane cell envelope is a defining feature of mycobacteria, it was only of late that the OM was disclosed to be a lipid bilayer (Bansal-Mutalik and Nikaido, 2014). S0031182016002377jrv 116..133

Amphiphilic xanthones as a potent chemical entity of antimycobacterial agents with membrane targeting properties. In the following paragraphs, we review these agents with regard to their SARs and mechanistic effects on the mycobacterial membranes. Microbiol., 19 July 2018 6 0 obj << The same profile was observed for verapamil. /Type /Page <<

>> << << >>

/Rotate 0 /Parent 10 0 R endobj << /Names [ 165 0 R 166 0 R 167 0 R 168 0 R 169 0 R 215 0 R 216 0 R 217 0 R 218 0 R 219 0 R Thus n-decyl TPP and phenylhexyl TPP cations had MICs that were comparable to 9 and 10. Annu Rev Biochem 1995; 64: 29-63. Exochelins of Mycobacterium tuberculosis remove iron from human iron-binding proteins and donate iron to mycobactins in the M. tuberculosis cell wall. >> In the first class are agents that interact directly with the bacterial membrane bilayer to disrupt its architectural organization and functionality.
%PDF-1.3 >> machinery of MTB. endobj >> /D [32 0 R /FitR 47 108 289 82] J. Med. The glfT1 gene from M. smegmatis mc2155 was amplified based on the oligonucleotide primers 5′-GCACCAACATATGACGCACACTGAGGTCGTCTG-3′ and 5′-CCCAAGCTTTCATCGCTGGAACCTTTCGCGTC-3′, containing NdeI and HindIII restriction sites. Biomed Pharmacother 2017; 91: 546-58. We investigated this question through enzyme incubations containing GlfT2 from M. tuberculosis overexpressed in E. coli (32), radiolabeled GL-4 or GL-5 (2,000 dpm each), and 0.2 mM cold UDP-Galp instead of the radioactive counterpart. <<

<< Reddy VM, Kumar B. Interaction of Mycobacterium avium complex with human respiratory epithelial cells. 175 0 R 176 0 R 177 0 R 178 0 R 179 0 R 223 0 obj endobj endobj /Count -13 Pore formation compromises the integrity of the membrane by increasing its permeability. 201, 1225–1231. endobj

>> Microbiol. HC, SN, ML, PG, DA, TY, WM, and MG planned and conducted the experiments in our reported work. >> Recognition of the dual β-(1→4) and β-(1→5) Galf transferase activities of GlfT1.

doi: 10.1371/journal.pone.0034538, Madak, J. T., and Neamati, N. (2015). << /CropBox [0 0 595.276 841.89] >> fractions proteins gels of m. tuberculosis. >> endobj 60, 8456–8465. << >> An ideR mutant of Mycobacterium smegmatis has derepressed siderophore production and an altered oxidative-stress response. endobj doi: 10.1073/pnas.150518097, Pasca, M. R., Guglierame, P., Arcesi, F., Bellinzoni, M., De Rossi, E., and Riccardi, G. (2004). Zebrafish Embryo Model for Assessment of Drug Efficacy on Mycobacterial Persisters. >> Under such >> endobj

Chem. Q. Rev.