363
Views
8
CrossRef citations to date
0
Altmetric
Review Articles

Mycobacterial ethambutol responsive genes and implications in antibiotics resistance

, , , &
Pages 284-293 | Received 24 May 2020, Accepted 17 Nov 2020, Published online: 03 Dec 2020

References

  • Zignol M, van Gemert W, Falzon D, et al. Surveillance of anti-tuberculosis drug resistance in the world: an updated analysis, 2007–2010. Bull World Health Organ. 2012;90(2):111–119D.
  • Sethi S, Mewara A, Dhatwalia SK, et al. Prevalence of multidrug resistance in Mycobacterium tuberculosis isolates from HIV seropositive and seronegative patients with pulmonary tuberculosis in north India. BMC Infect Dis. 2013;13:137.
  • Global tuberculosis report; 2019. Available from: https://www.who.int/publications/i/item/global-tuberculosis-report-2019
  • Wilson TM. Clinical experience with ethambutol. Antibiot Chemother. 1970;16:222–229.
  • Masur H. Recommendations on prophylaxis and therapy for disseminated Mycobacterium avium complex disease in patients infected with the human immunodeficiency virus. Public Health Service Task Force on Prophylaxis and Therapy for Mycobacterium avium Complex. N Engl J Med. 1993;329(12):898–904.
  • Thomas JP, Baughn CO, Wilkinson RG, et al. A new synthetic compound with antituberculous activity in mice: ethambutol (dextro-2,2′-(ethylenediimino)-di-l-butanol). Am Rev Respir Dis. 1961;83:891–893.
  • Ahmad S, Mokaddas E, Al-Mutairi N, et al. Discordance across phenotypic and molecular methods for drug susceptibility testing of drug-resistant Mycobacterium tuberculosis isolates in a low TB incidence country. PLoS One. 2016;11(4):e0153563.
  • Ahmad S, Jaber AA, Mokaddas E. Frequency of embB codon 306 mutations in ethambutol-susceptible and -resistant clinical Mycobacterium tuberculosis isolates in Kuwait. Tuberculosis (Edinb). 2007;87(2):123–129.
  • Telenti A, Philipp WJ, Sreevatsan S, et al. The emb operon, a gene cluster of Mycobacterium tuberculosis involved in resistance to ethambutol. Nat Med. 1997;3(5):567–570.
  • Belanger AE, Besra GS, Ford ME, et al. The embAB genes of Mycobacterium avium encode an arabinosyl transferase involved in cell wall arabinan biosynthesis that is the target for the antimycobacterial drug ethambutol. Proc Natl Acad Sci U S A. 1996;93(21):11919–11924.
  • Cheng S, Cui Z, Li Y, et al. Diagnostic accuracy of a molecular drug susceptibility testing method for the antituberculosis drug ethambutol: a systematic review and meta-analysis. J Clin Microbiol. 2014;52(8):2913–2924.
  • Pharmacokinetics of ethambutol; 2020. Available from: http://drugs.medlive.cn/drugref/html/14405.shtml
  • Zhu M, Burman WJ, Starke JR, et al. Pharmacokinetics of ethambutol in children and adults with tuberculosis. Int J Tuberc Lung Dis. 2004;8(11):1360–1367.
  • Perlman DC, Segal Y, Rosenkranz S, et al. The clinical pharmacokinetics of rifampin and ethambutol in HIV-infected persons with tuberculosis. Clin Infect Dis. 2005;41(11):1638–1647.
  • McIlleron H, Wash P, Burger A, et al. Determinants of rifampin, isoniazid, pyrazinamide, and ethambutol pharmacokinetics in a cohort of tuberculosis patients. Antimicrob Agents Chemother. 2006;50(4):1170–1177.
  • Talbert Estlin KA, Sadun AA. Risk factors for ethambutol optic toxicity. Int Ophthalmol. 2010;30(1):63–72.
  • Martin SJ, Bowden FJ. Ethambutol toxicity manifesting as acute onset psychosis. Int J STD Aids. 2007;18(4):287–288.
  • Chan RY, Kwok AK. Ocular toxicity of ethambutol. Hong Kong Med J. 2006;12(1):56–60.
  • Chung H, Yoon YH, Hwang JJ, et al. Ethambutol-induced toxicity is mediated by zinc and lysosomal membrane permeabilization in cultured retinal cells. Toxicol Appl Pharmacol. 2009;235(2):163–170.
  • Yoon YH, Jung KH, Sadun AA, et al. Ethambutol-induced vacuolar changes and neuronal loss in rat retinal cell culture: mediation by endogenous zinc. Toxicol Appl Pharmacol. 2000;162(2):107–114.
  • Tsai RK, Chang CH, Hseu CM, et al. Ethambutol induces PKC-dependent cytotoxic and antiproliferative effects on human retinal pigment cells. Exp Eye Res. 2008;87(6):594–603.
  • Chatterjee D. The mycobacterial cell wall: structure, biosynthesis and sites of drug action. Curr Opin Chem Biol. 1997;1(4):579–588.
  • Jankute M, Grover S, Rana AK, et al. Arabinogalactan and lipoarabinomannan biosynthesis: structure, biogenesis and their potential as drug targets. Future Microbiol. 2012;7(1):129–147.
  • Mikusova K, Slayden RA, Besra GS, et al. Biogenesis of the mycobacterial cell wall and the site of action of ethambutol. Antimicrob Agents Chemother. 1995;39(11):2484–2489.
  • Takayama K, Kilburn JO. Inhibition of synthesis of arabinogalactan by ethambutol in Mycobacterium smegmatis. Antimicrob Agents Chemother. 1989;33(9):1493–1499.
  • Alderwick LJ, Radmacher E, Seidel M, et al. Deletion of Cg-emb in Corynebacterianeae leads to a novel truncated cell wall arabinogalactan, whereas inactivation of Cg-ubiA results in an arabinan-deficient mutant with a cell wall galactan core. J Biol Chem. 2005;280(37):32362–32371.
  • Berg S, Starbuck J, Torrelles JB, et al. Roles of conserved proline and glycosyltransferase motifs of EmbC in biosynthesis of lipoarabinomannan. J Biol Chem. 2005;280(7):5651–5663.
  • Escuyer VE, Lety MA, Torrelles JB, et al. 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.
  • Srivastava S, Ayyagari A, Dhole TN, et al. emb nucleotide polymorphisms and the role of embB306 mutations in Mycobacterium tuberculosis resistance to ethambutol. Int J Med Microbiol. 2009;299(4):269–280.
  • Zhao LL, Sun Q, Liu HC, et al. Analysis of embCAB mutations associated with ethambutol resistance in multidrug-resistant Mycobacterium tuberculosis isolates from China. Antimicrob Agents Chemother. 2015;59(4):2045–2050.
  • Park YK, Ryoo SW, Lee SH, et al. Correlation of the phenotypic ethambutol susceptibility of Mycobacterium tuberculosis with embB gene mutations in Korea. J Med Microbiol. 2012;61(Pt 4):529–534.
  • Tessema B, Beer J, Emmrich F, et al. Analysis of gene mutations associated with isoniazid, rifampicin and ethambutol resistance among Mycobacterium tuberculosis isolates from Ethiopia. BMC Infect Dis. 2012;12:37.
  • Chaoui I, Sabouni R, Kourout M, et al. Analysis of isoniazid, streptomycin and ethambutol resistance in Mycobacterium tuberculosis isolates from Morocco. J Infect Dev Ctries. 2009;3(4):278–284.
  • Sugawara I, Otomo K, Yamada H, et al. The molecular epidemiology of ethambutol-resistant Mycobacterium tuberculosis in Henan Province, China. Jpn J Infect Dis. 2005;58(6):393–395.
  • Jadaun GP, Das R, Upadhyay P, et al. Role of embCAB gene mutations in ethambutol resistance in Mycobacterium tuberculosis isolates from India. Int J Antimicrob Agents. 2009;33(5):483–486.
  • Plinke C, Cox HS, Zarkua N, et al. embCAB sequence variation among ethambutol-resistant Mycobacterium tuberculosis isolates without embB306 mutation. J Antimicrob Chemother. 2010;65(7):1359–1367.
  • Safi H, Sayers B, Hazbon MH, et al. Transfer of embB codon 306 mutations into clinical Mycobacterium tuberculosis strains alters susceptibility to ethambutol, isoniazid, and rifampin. Antimicrob Agents Chemother. 2008;52(6):2027–2034.
  • Nebenzahl-Guimaraes H, Jacobson KR, Farhat MR, et al. Systematic review of allelic exchange experiments aimed at identifying mutations that confer drug resistance in Mycobacterium tuberculosis. J Antimicrob Chemother. 2014;69(2):331–342.
  • Safi H, Fleischmann RD, Peterson SN, et al. Allelic exchange and mutant selection demonstrate that common clinical embCAB gene mutations only modestly increase resistance to ethambutol in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2010;54(1):103–108.
  • Cuevas-Cordoba B, Juarez-Eusebio DM, Almaraz-Velasco R, et al. Mutation at embB codon 306, a potential marker for the identification of multidrug resistance associated with ethambutol in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2015;59(9):5455–5462.
  • Sreevatsan S, Stockbauer KE, Pan X, et al. Ethambutol resistance in Mycobacterium tuberculosis: critical role of embB mutations. Antimicrob Agents Chemother. 1997;41(8):1677–1681.
  • Al-Mutairi NM, Ahmad S, Mokaddas E. Molecular screening versus phenotypic susceptibility testing of multidrug-resistant Mycobacterium tuberculosis isolates for streptomycin and ethambutol. Microb Drug Resist. 2018;24(7):923–931.
  • Xu Y, Jia H, Huang H, et al. Mutations found in embCAB, embR, and ubiA genes of ethambutol-sensitive and -resistant Mycobacterium tuberculosis clinical isolates from China. Biomed Res Int. 2015;2015:951706.
  • Ramaswamy SV, Amin AG, Goksel S, et al. Molecular genetic analysis of nucleotide polymorphisms associated with ethambutol resistance in human isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2000;44(2):326–336.
  • Brossier F, Sougakoff W, Bernard C, et al. Molecular analysis of the embCAB locus and embR gene involved in ethambutol resistance in clinical isolates of Mycobacterium tuberculosis in France. Antimicrob Agents Chemother. 2015;59(8):4800–4808.
  • Cui Z, Li Y, Cheng S, et al. Mutations in the embC–embA intergenic region contribute to Mycobacterium tuberculosis resistance to ethambutol. Antimicrob Agents Chemother. 2014;58(11):6837–6843.
  • Moure R, Espanol M, Tudo G, et al. Characterization of the embB gene in Mycobacterium tuberculosis isolates from Barcelona and rapid detection of main mutations related to ethambutol resistance using a low-density DNA array-authors' response. J Antimicrob Chemother. 2014;69(8):2299–2300.
  • Weiling H, Xiaowen Y, Chunmei L, et al. Function and evolution of ubiquitous bacterial signaling adapter phosphopeptide recognition domain FHA. Cell Signal. 2013;25(3):660–665.
  • Sharma K, Gupta M, Krupa A, et al. EmbR, a regulatory protein with ATPase activity, is a substrate of multiple serine/threonine kinases and phosphatase in Mycobacterium tuberculosis. FEBS J. 2006;273(12):2711–2721.
  • Alderwick LJ, Molle V, Kremer L, et al. Molecular structure of EmbR, a response element of Ser/Thr kinase signaling in Mycobacterium tuberculosis. Proc Natl Acad Sci USA. 2006;103(8):2558–2563.
  • Molle V, Reynolds RC, Alderwick LJ, et al. EmbR2, a structural homologue of EmbR, inhibits the Mycobacterium tuberculosis kinase/substrate pair PknH/EmbR. Biochem J. 2008;410(2):309–317.
  • Sharma K, Gupta M, Pathak M, et al. Transcriptional control of the mycobacterial embCAB operon by PknH through a regulatory protein, EmbR, in vivo. J Bacteriol. 2006;188(8):2936–2944.
  • Song N, Li Z, Cui Z, et al. The prominent alteration in transcriptome and metabolome of Mycobacterium bovis BCG str. Tokyo 172 induced by vitamin B1. BMC Microbiol. 2019;19(1):104.
  • Betts JC, McLaren A, Lennon MG, et al. Signature gene expression profiles discriminate between isoniazid-, thiolactomycin-, and triclosan-treated Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2003;47(9):2903–2913.
  • Fu LM. Exploring drug action on Mycobacterium tuberculosis using affymetrix oligonucleotide genechips. Tuberculosis (Edinb). 2006;86(2):134–143.
  • Jeeves RE, Marriott AA, Pullan ST, et al. Mycobacterium tuberculosis is resistant to isoniazid at a slow growth rate by single nucleotide polymorphisms in katG codon Ser315. PLoS One. 2015;10(9):e0138253.
  • Jousselin A, Renzoni A, Andrey DO, et al. The posttranslocational chaperone lipoprotein PrsA is involved in both glycopeptide and oxacillin resistance in Staphylococcus aureus. Antimicrob Agents Chemother. 2012;56(7):3629–3640.
  • Munoz-Elias EJ, Upton AM, Cherian J, et al. Role of the methylcitrate cycle in Mycobacterium tuberculosis metabolism, intracellular growth, and virulence. Mol Microbiol. 2006;60(5):1109–1122.
  • Tang S, Hicks ND, Cheng YS, et al. Structural and functional insight into the Mycobacterium tuberculosis protein PrpR reveals a novel type of transcription factor. Nucleic Acids Res. 2019;47(18):9934–9949.
  • Zhang H, Li D, Zhao L, et al. Genome sequencing of 161 Mycobacterium tuberculosis isolates from China identifies genes and intergenic regions associated with drug resistance. Nat Genet. 2013;45(10):1255–1260.
  • Honeyborne I, McHugh TD, Kuittinen I, et al. Profiling persistent tubercule bacilli from patient sputa during therapy predicts early drug efficacy. BMC Med. 2016;14:68.
  • Xu Y, Liu F, Chen S, et al. In vivo evolution of drug-resistant Mycobacterium tuberculosis in patients during long-term treatment. BMC Genomics. 2018;19(1):640.
  • Dubey VS, Sirakova TD, Cynamon MH, et al. Biochemical function of msl5 (pks8 plus pks17) in Mycobacterium tuberculosis H37Rv: biosynthesis of monomethyl branched unsaturated fatty acids. J Bacteriol. 2003;185(15):4620–4625.
  • Chiarelli LR, Mori G, Orena BS, et al. A multitarget approach to drug discovery inhibiting Mycobacterium tuberculosis PyrG and PanK. Sci Rep. 2018;8(1):3187.
  • Ramon-Garcia S, Mick V, Dainese E, et al. Functional and genetic characterization of the tap efflux pump in Mycobacterium bovis BCG. Antimicrob Agents Chemother. 2012;56(4):2074–2083.
  • Jiang X, Zhang W, Zhang Y, et al. Assessment of efflux pump gene expression in a clinical isolate Mycobacterium tuberculosis by real-time reverse transcription PCR. Microb Drug Resist. 2008;14(1):7–11.
  • Gupta AK, Katoch VM, Chauhan DS, et al. Microarray analysis of efflux pump genes in multidrug-resistant Mycobacterium tuberculosis during stress induced by common anti-tuberculous drugs. Microb Drug Resist. 2010;16(1):21–28.
  • Fikret Şahinkiyan M. The roles of efflux systems in extensively drug-resistant Mycobacterium tuberculosis. Turk J Mol Biol Biotechnol. 2017;2:71–81.
  • Pisu D, Provvedi R, Espinosa DM, et al. The alternative sigma factors SigE and SigB are involved in tolerance and persistence to antitubercular drugs. Antimicrob Agents Chemother. 2017;61(12):AAC.01596-17.
  • Duncan C, Jamieson FB, Troudt J, et al. Whole transcriptomic and proteomic analyses of an isogenic M. tuberculosis clinical strain with a naturally occurring 15 Kb genomic deletion. PLoS One. 2017;12(6):e0179996.
  • Skvortsov TA, Ignatov DV, Majorov KB, et al. Mycobacterium tuberculosis transcriptome profiling in mice with genetically different susceptibility to tuberculosis. Acta Nat. 2013;5(2):62–69.
  • Huang H, Berg S, Spencer JS, et al. Identification of amino acids and domains required for catalytic activity of DPPR synthase, a cell wall biosynthetic enzyme of Mycobacterium tuberculosis. Microbiology (Reading). 2008;154(Pt 3):736–743.
  • Lingaraju S, Rigouts L, Gupta A, et al. Geographic differences in the contribution of ubiA mutations to high-level ethambutol resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2016;60(7):4101–4105.
  • Safi H, Lingaraju S, Amin A, et al. Evolution of high-level ethambutol-resistant tuberculosis through interacting mutations in decaprenylphosphoryl-β-d-arabinose biosynthetic and utilization pathway genes. Nat Genet. 2013;45(10):1190–1197.
  • He L, Wang X, Cui P, et al. ubiA (Rv3806c) encoding DPPR synthase involved in cell wall synthesis is associated with ethambutol resistance in Mycobacterium tuberculosis. Tuberculosis (Edinb). 2015;95(2):149–154.
  • Wang M, Guo X, Yang X, et al. Mycobacterial dynamin-like protein IniA mediates membrane fission. Nat Commun. 2019;10(1):3906.
  • Ahmad S, Mokaddas E, Jaber AA. Rapid detection of ethambutol-resistant Mycobacterium tuberculosis strains by PCR-RFLP targeting embB codons 306 and 497 and iniA codon 501 mutations. Mol Cell Probes. 2004;18(5):299–306.
  • Jaber AA, Ahmad S, Mokaddas E. Minor contribution of mutations at iniA codon 501 and embC–embA intergenic region in ethambutol-resistant clinical Mycobacterium tuberculosis isolates in Kuwait. Ann Clin Microbiol Antimicrob. 2009;8:2.
  • Wang R, Marcotte EM. The proteomic response of Mycobacterium smegmatis to anti-tuberculosis drugs suggests targeted pathways. J Proteome Res. 2008;7(3):855–865.
  • Boshoff HI, Myers TG, Copp BR, et al. The transcriptional responses of Mycobacterium tuberculosis to inhibitors of metabolism: novel insights into drug mechanisms of action. J Biol Chem. 2004;279(38):40174–40184.
  • Ojha A, Anand M, Bhatt A, et al. GroEL1: a dedicated chaperone involved in mycolic acid biosynthesis during biofilm formation in mycobacteria. Cell. 2005;123(5):861–873.
  • Jiang T, Zhan Y, Sun M, et al. The novel responses of ethambutol against Mycobacterium smegmatis mc2155 revealed by proteomics analysis. Curr Microbiol. 2011;62(2):341–345.
  • Gorla P, Plocinska R, Sarva K, et al. MtrA response regulator controls cell division and cell wall metabolism and affects susceptibility of mycobacteria to the first line antituberculosis drugs. Front Microbiol. 2018;9:2839.
  • Brocker M, Bott M. Evidence for activator and repressor functions of the response regulator MtrA from Corynebacterium glutamicum. FEMS Microbiol Lett. 2006;264(2):205–212.
  • Moker N, Brocker M, Schaffer S, et al. Deletion of the genes encoding the MtrA–MtrB two-component system of Corynebacterium glutamicum has a strong influence on cell morphology, antibiotics susceptibility and expression of genes involved in osmoprotection. Mol Microbiol. 2004;54(2):420–438.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.