Comparison of gene expression profiles between pansensitive and multidrug-resistant strains of Mycobacterium tuberculosis.

K Peñuelas-Urquides, L González-Escalante, L Villarreal-Treviño, B Silva-Ramírez, D J Gutiérrez-Fuentes, R Mojica-Espinosa, C Rangel-Escareño, L Uribe-Figueroa, G M Molina-Salinas, J Dávila-Velderrain, F Castorena-Torres, M Bermúdez de León, S Said-Fernández
Author Information
  1. K Peñuelas-Urquides: Departamento de Biología Molecular, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Calle 2 de abril 501, Col. Independencia, 64720, Monterrey, Nuevo León, Mexico.

Abstract

Mycobacterium tuberculosis has developed resistance to anti-tuberculosis first-line drugs. Multidrug-resistant strains complicate the control of tuberculosis and have converted it into a worldwide public health problem. Mutational studies of target genes have tried to envisage the resistance in clinical isolates; however, detection of these mutations in some cases is not sufficient to identify drug resistance, suggesting that other mechanisms are involved. Therefore, the identification of new markers of susceptibility or resistance to first-line drugs could contribute (1) to specifically diagnose the type of M. tuberculosis strain and prescribe an appropriate therapy, and (2) to elucidate the mechanisms of resistance in multidrug-resistant strains. In order to identify specific genes related to resistance in M. tuberculosis, we compared the gene expression profiles between the pansensitive H37Rv strain and a clinical CIBIN:UMF:15:99 multidrug-resistant isolate using microarray analysis. Quantitative real-time PCR confirmed that in the clinical multidrug-resistant isolate, the esxG, esxH, rpsA, esxI, and rpmI genes were upregulated, while the lipF, groES, and narG genes were downregulated. The modified genes could be involved in the mechanisms of resistance to first-line drugs in M. tuberculosis and could contribute to increased efficiency in molecular diagnosis approaches of infections with drug-resistant strains.

References

  1. Arch Med Res. 2006 Jan;37(1):45-9 [PMID: 16314185]
  2. Tuberculosis (Edinb). 2004;84(3-4):263-74 [PMID: 15207496]
  3. PLoS Pathog. 2010 Jul 08;6(7):e1000988 [PMID: 20628579]
  4. Int J Tuberc Lung Dis. 2011 Feb;15(2):205-10, i [PMID: 21219682]
  5. Genome Biol. 2007;8(12):R265 [PMID: 18078514]
  6. Infect Immun. 2003 Mar;71(3):1379-88 [PMID: 12595455]
  7. BMC Microbiol. 2009 Mar 04;9:48 [PMID: 19257911]
  8. Antimicrob Agents Chemother. 2003 Sep;47(9):2903-13 [PMID: 12936993]
  9. Jpn J Infect Dis. 2008 Jul;61(4):264-8 [PMID: 18653966]
  10. Arch Biochem Biophys. 2004 Apr 15;424(2):226-34 [PMID: 15047195]
  11. PLoS Pathog. 2011 Nov;7(11):e1002342 [PMID: 22072964]
  12. J Clin Microbiol. 1993 Feb;31(2):406-9 [PMID: 8381814]
  13. J Infect Dev Ctries. 2009 May 01;3(4):278-84 [PMID: 19759491]
  14. Braz J Microbiol. 2013 May 31;44(1):287-9 [PMID: 24159318]
  15. Infect Immun. 2002 Jan;70(1):286-91 [PMID: 11748194]
  16. PLoS Pathog. 2011 Sep;7(9):e1002262 [PMID: 21949656]
  17. J Bacteriol. 2001 Dec;183(24):7371-80 [PMID: 11717296]
  18. Nucleic Acids Res. 2003 Feb 15;31(4):e15 [PMID: 12582260]
  19. J Clin Microbiol. 1997 Apr;35(4):907-14 [PMID: 9157152]
  20. J Biol Chem. 2011 Aug 26;286(34):29993-30002 [PMID: 21730061]
  21. Clin Microbiol Infect. 2009 Jan;15 Suppl 1:66-8 [PMID: 19220360]
  22. EURASIP J Bioinform Syst Biol. 2007;:23054 [PMID: 18253472]
  23. BMC Microbiol. 2007 May 14;7:37 [PMID: 17501996]
  24. Tuberculosis (Edinb). 2005 Sep-Nov;85(5-6):385-94 [PMID: 16253564]
  25. Microbiology (Reading). 2005 Jan;151(Pt 1):5-14 [PMID: 15632420]
  26. J Clin Microbiol. 2009 Jun;47(6):1767-72 [PMID: 19386845]
  27. Nat Med. 1997 May;3(5):567-70 [PMID: 9142129]
  28. Methods. 2001 Dec;25(4):402-8 [PMID: 11846609]
  29. Antimicrob Agents Chemother. 2011 Dec;55(12):5654-9 [PMID: 21911575]
  30. Toxicol In Vitro. 2008 Mar;22(2):411-21 [PMID: 18494146]
  31. Science. 2011 Sep 16;333(6049):1630-2 [PMID: 21835980]
  32. Stat Appl Genet Mol Biol. 2004;3:Article3 [PMID: 16646809]
  33. Respir Res. 2001;2(3):164-8 [PMID: 11686881]
  34. BMC Genomics. 2007 Mar 30;8:88 [PMID: 17397532]
  35. J Clin Microbiol. 2005 Aug;43(8):4010-4 [PMID: 16081943]

MeSH Term

Drug Resistance, Multiple, Bacterial
Genes, Bacterial
Mycobacterium tuberculosis
Real-Time Polymerase Chain Reaction
Transcriptome

Word Cloud

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