Skip to main content

Advertisement

SpringerLink
Log in

Comparison of Gene Expression Profiles Between Pansensitive and Multidrug-Resistant Strains of Mycobacterium tuberculosis

  • Published:
Current Microbiology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ali A, Hasan R, Jabeen K, Jabeen N, Qadeer E, Hasan Z (2011) Characterization of mutations conferring extensive drug resistance to Mycobacterium tuberculosis isolates in Pakistan. Antimicrob Agents Chemother 55(12):5654–5659

    Article  PubMed  CAS  Google Scholar 

  2. Arnvig KB, Comas I, Thomson NR, Houghton J, Boshoff HI, Croucher NJ, Rose G, Perkins TT, Parkhill J, Dougan G, Young DB (2011) Sequence-based analysis uncovers an abundance of non-coding RNA in the total transcriptome of Mycobacterium tuberculosis. PLoS Pathog 7(11):e1002342

    Article  PubMed  CAS  Google Scholar 

  3. Bailey SL, Roper MH, Huayta M, Trejos N, Lopez Alarcon V, Moore DA (2011) Missed opportunities for tuberculosis diagnosis. Int J Tuberc Lung Dis 15(2):205–210, i

    Google Scholar 

  4. Betts JC, McLaren A, Lennon MG, Kelly FM, Lukey PT, Blakemore SJ, Duncan K (2003) Signature gene expression profiles discriminate between isoniazid-, thiolactomycin-, and triclosan-treated Mycobacterium tuberculosis. Antimicrob Agents Chemother 47(9):2903–2913

    Article  PubMed  CAS  Google Scholar 

  5. Castorena-Torres F, Bermudez de Leon M, Cisneros B, Zapata-Perez O, Salinas JE, Albores A (2008) Changes in gene expression induced by polycyclic aromatic hydrocarbons in the human cell lines HepG2 and A549. Toxicol In Vitro 22(2):411–421

    Article  PubMed  CAS  Google Scholar 

  6. Chaoui I, Sabouni R, Kourout M, Jordaan AM, Lahlou O, Elouad R, Akrim M, Victor TC, El Mzibri M (2009) Analysis of isoniazid, streptomycin and ethambutol resistance in Mycobacterium tuberculosis isolates from Morocco. J Infect Dev Ctries 3(4):278–284

    PubMed  CAS  Google Scholar 

  7. Fritz C, Maass S, Kreft A, Bange FC (2002) Dependence of Mycobacterium bovis BCG on anaerobic nitrate reductase for persistence is tissue specific. Infect Immun 70(1):286–291

    Article  PubMed  CAS  Google Scholar 

  8. Fu LM, Fu-Liu CS (2007) The gene expression data of Mycobacterium tuberculosis based on Affymetrix gene chips provide insight into regulatory and hypothetical genes. BMC Microbiol 7:37

    Article  PubMed  Google Scholar 

  9. Fu LM, Shinnick TM (2007) Genome-wide analysis of intergenic regions of Mycobacterium tuberculosis H37Rv using Affymetrix GeneChips. EURASIP J Bioinform Syst Biol: 23054

  10. Gagneux S (2009) Fitness cost of drug resistance in Mycobacterium tuberculosis. Clin Microbiol Infect 15(Suppl 1):66–68

    Article  PubMed  Google Scholar 

  11. Gao Q, Kripke KE, Saldanha AJ, Yan W, Holmes S, Small PM (2005) Gene expression diversity among Mycobacterium tuberculosis clinical isolates. Microbiology 151(Pt 1):5–14

    Article  PubMed  CAS  Google Scholar 

  12. Goh KS, Rastogi N, Berchel M, Huard RC, Sola C (2005) Molecular evolutionary history of tubercle bacilli assessed by study of the polymorphic nucleotide within the nitrate reductase (narGHJI) operon promoter. J Clin Microbiol 43(8):4010–4014

    Article  PubMed  CAS  Google Scholar 

  13. Guo JH, Xiang WL, Zhao QR, Luo T, Huang M, Zhang J, Zhao J, Yang ZR, Sun Q (2008) Molecular characterization of drug-resistant Mycobacterium tuberculosis isolates from Sichuan Province in china. Jpn J Infect Dis 61(4):264–268

    PubMed  CAS  Google Scholar 

  14. Hillemann D, Rusch-Gerdes S, Richter E (2009) Feasibility of the GenoType MTBDRsl assay for fluoroquinolone, amikacin-capreomycin, and ethambutol resistance testing of Mycobacterium tuberculosis strains and clinical specimens. J Clin Microbiol 47(6):1767–1772

    Article  PubMed  CAS  Google Scholar 

  15. Homolka S, Niemann S, Russell DG, Rohde KH (2010) Functional genetic diversity among Mycobacterium tuberculosis complex clinical isolates: delineation of conserved core and lineage-specific transcriptomes during intracellular survival. PLoS Pathog 6(7):e1000988

    Article  PubMed  Google Scholar 

  16. Ilghari D, Lightbody KL, Veverka V, Waters LC, Muskett FW, Renshaw PS, Carr MD (2011) Solution structure of the Mycobacterium tuberculosis EsxG.EsxH complex: functional implications and comparisons with other M. tuberculosis Esx family complexes. J Biol Chem 286(34):29993–30002

    Article  PubMed  CAS  Google Scholar 

  17. Irizarry RA, Bolstad BM, Collin F, Cope LM, Hobbs B, Speed TP (2003) Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res 31(4):e15

    Article  PubMed  Google Scholar 

  18. Kamerbeek J, Schouls L, Kolk A, van Agterveld M, van Soolingen D, Kuijper S, Bunschoten A, Molhuizen H, Shaw R, Goyal M, van Embden J (1997) Simultaneous detection and strain differentiation of Mycobacterium tuberculosis for diagnosis and epidemiology. J Clin Microbiol 35(4):907–914

    PubMed  CAS  Google Scholar 

  19. Lee JM, Zhang S, Saha S, Santa Anna S, Jiang C, Perkins J (2001) RNA expression analysis using an antisense Bacillus subtilis genome array. J Bacteriol 183(24):7371–7380

    Article  PubMed  CAS  Google Scholar 

  20. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25(4):402–408

    Article  PubMed  CAS  Google Scholar 

  21. Maciag A, Piazza A, Riccardi G, Milano A (2009) Transcriptional analysis of ESAT-6 cluster 3 in Mycobacterium smegmatis. BMC Microbiol 9:48

    Article  PubMed  Google Scholar 

  22. Molina-Salinas GM, Ramos-Guerra MC, Vargas-Villarreal J, Mata-Cardenas BD, Becerril-Montes P, Said-Fernandez S (2006) Bactericidal activity of organic extracts from Flourensia cernua DC against strains of Mycobacterium tuberculosis. Arch Med Res 37(1):45–49

    Article  PubMed  Google Scholar 

  23. Park WD, Stegall MD (2007) A meta-analysis of kidney microarray datasets: investigation of cytokine gene detection and correlation with rt-PCR and detection thresholds. BMC Genomics 8:88

    Article  PubMed  Google Scholar 

  24. Peñuelas-Urquides K, Villarreal-Treviño L, Silva-Ramírez B, Rivadeneyra-Espinoza L, Said-Fernández S, Bermúdez de León M (2013) Measuring of Mycobacterium tuberculosis growth. A correlation of the optical measurements with colony forming units. Brazilian J Microbiol (in press)

  25. Qamra R, Mande SC, Coates AR, Henderson B (2005) The unusual chaperonins of Mycobacterium tuberculosis. Tuberculosis (Edinb) 85(5–6):385–394

    Article  CAS  Google Scholar 

  26. Saviola B, Woolwine SC, Bishai WR (2003) Isolation of acid-inducible genes of Mycobacterium tuberculosis with the use of recombinase-based in vivo expression technology. Infect Immun 71(3):1379–1388

    Article  PubMed  CAS  Google Scholar 

  27. Shi W, Zhang X, Jiang X, Yuan H, Lee JS, Barry CE 3rd, Wang H, Zhang W, Zhang Y (2011) Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis. Science 333(6049):1630–1632

    Article  PubMed  CAS  Google Scholar 

  28. Sidders B, Withers M, Kendall SL, Bacon J, Waddell SJ, Hinds J, Golby P, Movahedzadeh F, Cox RA, Frita R, Ten Bokum AM, Wernisch L, Stoker NG (2007) Quantification of global transcription patterns in prokaryotes using spotted microarrays. Genome Biol 8(12):R265

    Article  PubMed  Google Scholar 

  29. Smyth GK (2004) Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3: Article3

  30. Somoskovi A, Parsons LM, Salfinger M (2001) The molecular basis of resistance to isoniazid, rifampin, and pyrazinamide in Mycobacterium tuberculosis. Respir Res 2(3):164–168

    Article  PubMed  CAS  Google Scholar 

  31. Su T, Waxman DJ (2004) Impact of dimethyl sulfoxide on expression of nuclear receptors and drug-inducible cytochromes P450 in primary rat hepatocytes. Arch Biochem Biophys 424(2):226–234

    Article  PubMed  CAS  Google Scholar 

  32. Subbian S, Tsenova L, O’Brien P, Yang G, Koo MS, Peixoto B, Fallows D, Dartois V, Muller G, Kaplan G (2011) Phosphodiesterase-4 inhibition alters gene expression and improves isoniazid-mediated clearance of Mycobacterium tuberculosis in rabbit lungs. PLoS Pathog 7(9):e1002262

    Article  PubMed  CAS  Google Scholar 

  33. Telenti A, Philipp WJ, Sreevatsan S, Bernasconi C, Stockbauer KE, Wieles B, Musser JM, Jacobs WR Jr (1997) The emb operon, a gene cluster of Mycobacterium tuberculosis involved in resistance to ethambutol. Nat Med 3(5):567–570

    Article  PubMed  CAS  Google Scholar 

  34. van Embden JD, Cave MD, Crawford JT, Dale JW, Eisenach KD, Gicquel B, Hermans P, Martin C, McAdam R, Shinnick TM et al (1993) Strain identification of Mycobacterium tuberculosis by DNA fingerprinting: recommendations for a standardized methodology. J Clin Microbiol 31(2):406–409

    PubMed  Google Scholar 

  35. Waddell SJ, Stabler RA, Laing K, Kremer L, Reynolds RC, Besra GS (2004) The use of microarray analysis to determine the gene expression profiles of Mycobacterium tuberculosis in response to anti-bacterial compounds. Tuberculosis (Edinb) 84(3–4):263–274

    Article  Google Scholar 

  36. WHO (2012) Global Tuberculosis Report 2012. World Health Organization, Geneva

Download references

Acknowledgments

This study was supported by the National Council for Science and Technology (CONACyT), Mexico, Grant No. 99792.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. 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

    K. Peñuelas-Urquides, L. González-Escalante & M. Bermúdez de León

  2. Fac. de Biología, Universidad Autónoma de Nuevo León, UANL, Av. Universidad s/n Ciudad Universitaria, CP 66451, San Nicolás de los Garza, Nuevo León, Mexico

    K. Peñuelas-Urquides, L. González-Escalante & L. Villarreal-Treviño

  3. Departamento de Inmunogenética, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Calle 2 de abril 501, Col. Independencia, 64720, Monterrey, Nuevo León, Mexico

    B. Silva-Ramírez

  4. Instituto Nacional de Medicina Genómica, Periférico Sur 4809, Col. Arenal Tepepan, Delegación Tlalpan, 14610, Mexico, DF, Mexico

    D. J. Gutiérrez-Fuentes, R. Mojica-Espinosa, C. Rangel-Escareño & L. Uribe-Figueroa

  5. Departamento de Farmacognosia, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Calle 2 de abril 501, Col. Independencia, 64720, Monterrey, Nuevo León, Mexico

    G. M. Molina-Salinas

  6. Centro de Ciencias de la Complejidad C3, Universidad Nacional Autónoma de México, Av. Universidad 3000, Cd. Universitaria, Delegación Coyoacán, 04510, Mexico, DF, Mexico

    J. Dávila-Velderrain

  7. Instituto de Ecología, Universidad Nacional Autónoma de México, Av. Universidad 3000, Cd. Universitaria, Delegación Coyoacán, 04510, Mexico, DF, Mexico

    J. Dávila-Velderrain

  8. Escuela de Biotecnología y Alimentos, Tecnológico de Monterrey, Av. Eugenio Garza Sada No. 2501, Col. Tecnológico, 64849, Monterrey, Nuevo León, Mexico

    F. Castorena-Torres

  9. Cátedra de Cardiología y Medicina Vascular, Escuela de Medicina, Tecnológico de Monterrey, Batallón de San Patricio 112, Col. Valle de San Agustín, 66278, San Pedro Garza García, Nuevo León, Mexico

    F. Castorena-Torres

  10. Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Av. Francisco I. Madero y Dr. Eduardo Aguirre Pequeño, Col. Mitras Centro, 64460, Monterrey, Nuevo León, Mexico

    S. Said-Fernández

Authors
  1. K. Peñuelas-Urquides
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. González-Escalante
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Villarreal-Treviño
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B. Silva-Ramírez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. J. Gutiérrez-Fuentes
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R. Mojica-Espinosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C. Rangel-Escareño
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. L. Uribe-Figueroa
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. G. M. Molina-Salinas
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J. Dávila-Velderrain
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. F. Castorena-Torres
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. M. Bermúdez de León
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. S. Said-Fernández
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to M. Bermúdez de León or S. Said-Fernández.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peñuelas-Urquides, K., González-Escalante, L., Villarreal-Treviño, L. et al. Comparison of Gene Expression Profiles Between Pansensitive and Multidrug-Resistant Strains of Mycobacterium tuberculosis . Curr Microbiol 67, 362–371 (2013). https://doi.org/10.1007/s00284-013-0376-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00284-013-0376-8

Keywords

Search

Navigation