1887

Journal of Medical Microbiology logo

Volume 65, Issue 7

Compensatory expression of multidrug-resistance genes encoding ABC transporters in dermatophytes Free

Abstract

Genomic sequencing of several dermatophyte species has revealed that they show small differences in genetic content and genome organization, although each fungus has adapted to specific niches. Thus, it seemed relevant to compare gene expression between species. Here, we examined the transcription modulation of three ATP-binding cassette (ABC) transporter genes (, and ), which code for membrane transporter proteins in four species of ;,, and . These fungal species were challenged with sub-lethal doses of griseofulvin, itraconazole, terbinafine and amphotericin B. A mutant strain of , Δ, was also analysed for the modulation of and genes to evaluate the possible functional interaction among these three genes. Disruption of the gene resulted in the accumulation of high levels of transcripts when challenged with griseofulvin, suggesting that the gene is compensating for the inactivation of by providing resistance to this antifungal. Although the three ABC transporter genes have high homology between the four dermatophytes analysed, it is likely that they have specific functions, suggesting that the action of each drug is dependent on other factors inherent to each species. Our data suggest that these ABC transporter genes act synergistically in dermatophytes, and they may compensate for one another when challenged with antifungal drugs. This may be an important cause of therapeutic failure when treating fungal infections.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): Antifungal resistance , gene expression , griseofulvin , MDR , PDR and Trichophyton
© 2016 The Authors
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.000268
2016-07-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jmm/65/7/605.html?itemId=/content/journal/jmm/10.1099/jmm.0.000268&mimeType=html&fmt=ahah

References

  1. Cervelatti E. P., Fachin A. L., Ferreira-Nozawa M. S., Martinez-Rossi N. M. 2006; Molecular cloning and characterization of a novel ABC transporter gene in the human pathogen Trichophyton rubrum . Med Mycol 44:141–147 [View Article][PubMed]
     [Google Scholar]
  2. Coelho L. M., Aquino-Ferreira R., Maffei C. M., Martinez-Rossi N. M. 2008; In vitro antifungal drug susceptibilities of dermatophytes microconidia and arthroconidia. J Antimicrob Chemother 62:758–761 [View Article][PubMed]
     [Google Scholar]
  3. Fachin A. L., Contel E. P., Martinez-Rossi N. M. 2001; Effect of sub-MICs of antimycotics on expression of intracellular esterase of Trichophyton rubrum . Med Mycol 39:129–133 [View Article][PubMed]
     [Google Scholar]
  4. Fachin A. L., Ferreira-Nozawa M. S., Maccheroni W., Martinez-Rossi N. M. 2006; Role of the ABC transporter TruMDR2 in terbinafine, 4-nitroquinoline N-oxide and ethidium bromide susceptibility in Trichophyton rubrum . J Med Microbiol 55:1093–1099 [View Article][PubMed]
     [Google Scholar]
  5. Fernandez-Torres B., Carrillo A. J., Martin E., Del Palacio A., Moore M. K., Valverde A., Serrano M., Guarro J. 2001; In vitro activities of 10 antifungal drugs against 508 dermatophyte strains. Antimicrob Agents Chemother 45:2524–2528 [View Article]
     [Google Scholar]
  6. Gadzalski M., Ciesielska A., Staczek P. 2016; Bioinformatic survey of ABC transporters in dermatophytes. Gene 576:466–475 [View Article][PubMed]
     [Google Scholar]
  7. Grumbt M., Monod M., Staib P. 2011; Genetic advances in dermatophytes. FEMS Microbiol Lett 320:79–86 [View Article][PubMed]
     [Google Scholar]
  8. Higgins C. F. 1992; ABC transporters: from microorganisms to man. Annu Rev Cell Biol 8:67–113 [View Article][PubMed]
     [Google Scholar]
  9. Jacob T. R., Peres N. T., Persinoti G. F., Silva L. G., Mazucato M., Rossi A., Martinez-Rossi N. M. 2012; rpb2 is a reliable reference gene for quantitative gene expression analysis in the dermatophyte Trichophyton rubrum . Med Mycol 50:368–377 [View Article][PubMed]
     [Google Scholar]
  10. Jones M. M., Johnson A., Koszelak-Rosenblum M., Kirkham C., Brauer A. L., Malkowski M. G., Murphy T. F. 2014; Role of the oligopeptide permease ABC Transporter of Moraxella catarrhalis in nutrient acquisition and persistence in the respiratory tract. Infect Immun 82:4758–4766 [View Article][PubMed]
     [Google Scholar]
  11. Livak K. J., Schmittgen T. D. 2001; Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408 [View Article][PubMed]
     [Google Scholar]
  12. Maranhão F. C., Paião F. G., Martinez-Rossi N. M. 2007; Isolation of transcripts over-expressed in human pathogen Trichophyton rubrum during growth in keratin. Microb Pathog 43:166–172 [View Article][PubMed]
     [Google Scholar]
  13. Maranhão F. C., Paião F. G., Fachin A. L., Martinez-Rossi N. M. 2009; Membrane transporter proteins are involved in Trichophyton rubrum pathogenesis. J Med Microbiol 58:163–168 [View Article][PubMed]
     [Google Scholar]
  14. Martinez D. A., Oliver B. G., Gräser Y., Goldberg J. M., Li W., Martinez-Rossi N. M., Monod M., Shelest E., Barton R. C. et al. 2012; Comparative genome analysis of Trichophyton rubrum and related dermatophytes reveals candidate genes involved in infection. MBio 3: [View Article][PubMed]
     [Google Scholar]
  15. Martinez-Rossi N. M., Peres N. T., Rossi A. 2008; Antifungal resistance mechanisms in dermatophytes. Mycopathologia 166:369–383 [View Article][PubMed]
     [Google Scholar]
  16. Mendes N. S., Silva P. M., Silva-Rocha R., Martinez-Rossi N. M., Rossi A. 2016; Pre-mRNA splicing is modulated by antifungal drugs in the filamentous fungus Neurospora crassa . FEBS Open Bio 6:358–368 [View Article]
     [Google Scholar]
  17. Paião F. G., Segato F., Cursino-Santos J. R., Peres N. T., Martinez-Rossi N. M. 2007; Analysis of Trichophyton rubrum gene expression in response to cytotoxic drugs. FEMS Microbiol Lett 271:180–186 [View Article][PubMed]
     [Google Scholar]
  18. Peres N. T. A., Persinoti G. F., Lang E. A. S., Rossi A., Martinez-Rossi N. M., Passos G. A. 2015; Transcriptome in human mycoses. In Transcriptomics in Health and Disease pp. 227–263 Edited by Passos G. A. Springer International Publishing; Switzerland:
     [Google Scholar]
  19. Peres N. T., Sanches P. R., Falcão J. P., Silveira H. C., Paião F. G., Maranhão F. C., Gras D. E., Segato F., Cazzaniga R. A., other authors. 2010; Transcriptional profiling reveals the expression of novel genes in response to various stimuli in the human dermatophyte Trichophyton rubrum . BMC Microbiol 10:39 [View Article][PubMed]
     [Google Scholar]
  20. Persinoti G. F., de Aguiar Peres N. T., Jacob T. R., Rossi A., Vêncio R. Z., Martinez-Rossi N. M. 2014; RNA-sequencing analysis of Trichophyton rubrum transcriptome in response to sublethal doses of acriflavine. BMC Genomics 15:S1 [View Article][PubMed]
     [Google Scholar]
  21. Prasad R., Gaur N. A., Gaur M., Komath S. S. 2006; Efflux pumps in drug resistance of Candida . Infect Disord Drug Targets 6:69–83 [View Article][PubMed]
     [Google Scholar]
  22. Sanglard D., Ischer F., Monod M., Bille J. 1997; Cloning of Candida albicans genes conferring resistance to azole antifungal agents: characterization of CDR2, a new multidrug ABC transporter gene. Microbiology 143:405–416 [View Article][PubMed]
     [Google Scholar]
  23. Shapiro R. S., Robbins N., Cowen L. E. 2011; Regulatory circuitry governing fungal development, drug resistance, and disease. Microbiol Mol Biol Rev 75:213–267 [View Article][PubMed]
     [Google Scholar]
  24. Teles F., Seixas J. 2015; The future of novel diagnostics in medical mycology. J Med Microbiol 64:315–322 [View Article][PubMed]
     [Google Scholar]
  25. Wirsching S., Michel S., Köhler G., Morschhäuser J. 2000; Activation of the multiple drug resistance gene MDR1 in fluconazole-resistant, clinical Candida albicans strains is caused by mutations in a trans-regulatory factor. J Bacteriol 182:400–404[PubMed] [Crossref]
     [Google Scholar]
  26. Yibmantasiri P., Bircham P. W., Maass D. R., Bellows D. S., Atkinson P. H. 2014; Networks of genes modulating the pleiotropic drug response in Saccharomyces cerevisiae . Mol Biosyst 10:128–137 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.000268
Loading
Compensatory expression of multidrug-resistance genes encoding ABC transporters in dermatophytes
J. Med. Microbiol. 65, 605 (2016); https://doi.org/10.1099/jmm.0.000268
/content/journal/jmm/10.1099/jmm.0.000268
/content/journal/jmm/10.1099/jmm.0.000268
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error