1887

Abstract

is currently ranked as the second most frequently isolated aetiological agent of human fungal infections, next only to . In comparison with , shows lower susceptibility to azoles, the most common agents used in treatment of fungal infections. Interestingly, the mechanisms of resistance to azole agents in have been much better investigated than those in . The aim of the presented study was to determine the mechanisms of resistance to azoles in 81 clinical isolates from three different hospitals in Poland. The investigation was carried out with a Sensititre Yeast One test and revealed that 18 strains were resistant to fluconazole, and 15 were cross-resistant to all other azoles tested (voriconazole, posaconazole and itraconazole). One isolate resistant to fluconazole was cross-resistant to voriconazole, and resistance to voriconazole only was observed in six other isolates. All strains were found to be susceptible to echinocandins and amphotericin B, and five were classified as resistant to 5-fluorocytosine. The sequence of the gene encoding lanosterol 14-α demethylase (the molecular target of azoles) of 41 isolates, including all strains resistant to fluconazole and three resistant only to voriconazole, was determined, and no amino acid substitutions were found. Real-time PCR studies revealed that 13 of 15 azole-resistant strains showed upregulation of the gene encoding the efflux pump. No upregulation of expression of the or gene was observed.

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2015-06-01
2019-09-22
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References

  1. Arendrup M. C.. ( 2010;). Epidemiology of invasive candidiasis. . Curr Opin Crit Care 16:, 445–452 [CrossRef] [PubMed]
    [Google Scholar]
  2. Berila N., Subik J.. ( 2010;). Molecular analysis of Candida glabrata clinical isolates. . Mycopathologia 170:, 99–105 [CrossRef] [PubMed]
    [Google Scholar]
  3. Berila N., Borecka S., Dzugasova V., Bojnansky J., Subik J.. ( 2009;). Mutations in the CgPDR1 and CgERG11 genes in azole-resistant Candida glabrata clinical isolates from Slovakia. . Int J Antimicrob Agents 33:, 574–578 [CrossRef] [PubMed]
    [Google Scholar]
  4. Chavanet P., Lopez J., Grappin M., Bonnin A., Duong M., Waldner A., Buisson M., Camerlynck P., Portier H.. ( 1994;). Cross-sectional study of the susceptibility of Candida isolates to antifungal drugs and in vitro-in vivo correlation in HIV-infected patients. . AIDS 8:, 945–950 [CrossRef] [PubMed]
    [Google Scholar]
  5. CLSI ( 2012;). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, 4th informational supplement M27-S4. Wayne, PA:: Clinical Laboratory Standards Institute;.
    [Google Scholar]
  6. Costa C., Nunes J., Henriques A., Mira N. P., Nakayama H., Chibana H., Teixeira M. C.. ( 2014;). Candida glabrata drug: H+ antiporter CgTpo3 (ORF CAGL0I10384g): role in azole drug resistance and polyamine homeostasis. . J Antimicrob Chemother 69:, 1767–1776 [CrossRef] [PubMed]
    [Google Scholar]
  7. Dzierz˙anowska-Fangrat K., Romanowska E., Gryniewicz-Kwiatkowska O., Migdał M., Witulska K., Ryz˙ko J., Kaliciński P., Ksia˛z˙yk J., Nadkowska P., Dzierzanowska D.. ( 2014;). Candidaemia in a Polish tertiary paediatric hospital, 2000 to 2010. . Mycoses 57:, 105–109 [CrossRef] [PubMed]
    [Google Scholar]
  8. Edlind T. D., Katiyar S. K.. ( 2010;). Mutational analysis of flucytosine resistance in Candida glabrata. . Antimicrob Agents Chemother 54:, 4733–4738 [CrossRef] [PubMed]
    [Google Scholar]
  9. Ferrari S., Sanguinetti M., De Bernardis F., Torelli R., Posteraro B., Vandeputte P., Sanglard D.. ( 2011;). Loss of mitochondrial functions associated with azole resistance in Candida glabrata results in enhanced virulence in mice. . Antimicrob Agents Chemother 55:, 1852–1860 [CrossRef] [PubMed]
    [Google Scholar]
  10. Hajjeh R. A., Sofair A. N., Harrison L. H., Lyon G. M., Arthington-Skaggs B. A., Mirza S. A., Phelan M., Morgan J., Lee-Yang W., other authors. ( 2004;). Incidence of bloodstream infections due to Candida species and in vitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program. . J Clin Microbiol 42:, 1519–1527 [CrossRef] [PubMed]
    [Google Scholar]
  11. Hull C. M., Parker J. E., Bader O., Weig M., Gross U., Warrilow A. G., Kelly D. E., Kelly S. L.. ( 2012;). Facultative sterol uptake in an ergosterol-deficient clinical isolate of Candida glabrata harboring a missense mutation in ERG11 and exhibiting cross-resistance to azoles and amphotericin B. . Antimicrob Agents Chemother 56:, 4223–4232 [CrossRef] [PubMed]
    [Google Scholar]
  12. Jabra-Rizk M. A.. ( 2006;). Fungal infections and drug resistance. . Emerg Med & Crit Care Rev 2:, 38–41.
    [Google Scholar]
  13. Kaur R., Castaño I., Cormack B. P.. ( 2004;). Functional genomic analysis of fluconazole susceptibility in the pathogenic yeast Candida glabrata: roles of calcium signaling and mitochondria. . Antimicrob Agents Chemother 48:, 1600–1613 [CrossRef] [PubMed]
    [Google Scholar]
  14. Kaur R., Domergue R., Zupancic M. L., Cormack B. P.. ( 2005;). A yeast by any other name: Candida glabrata and its interaction with the host. . Curr Opin Microbiol 8:, 378–384 [CrossRef] [PubMed]
    [Google Scholar]
  15. Lass-Flörl C.. ( 2009;). The changing face of epidemiology of invasive fungal disease in Europe. . Mycoses 52:, 197–205 [CrossRef] [PubMed]
    [Google Scholar]
  16. Livak K. J., Schmittgen T. D.. ( 2001;). Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔC T method. . Methods 25:, 402–408 [CrossRef] [PubMed]
    [Google Scholar]
  17. Marichal P., Vanden Bossche H., Odds F. C., Nobels G., Warnock D. W., Timmerman V., Van Broeckhoven C., Fay S., Mose-Larsen P.. ( 1997;). Molecular biological characterization of an azole-resistant Candida glabrata isolate. . Antimicrob Agents Chemother 41:, 2229–2237 [PubMed]
    [Google Scholar]
  18. Morio F., Loge C., Besse B., Hennequin C., Le Pape P.. ( 2010;). Screening for amino acid substitutions in the Candida albicans Erg11 protein of azole-susceptible and azole-resistant clinical isolates: new substitutions and a review of the literature. . Diagn Microbiol Infect Dis 66:, 373–384 [CrossRef] [PubMed]
    [Google Scholar]
  19. Olchawa A., Krawczyk B., Brillowska-Dabrowska A.. ( 2013;). New PCR test for detection of Candida glabrata based on the molecular target chosen by the RAPD technique. . Pol J Microbiol 62:, 81–84 [PubMed]
    [Google Scholar]
  20. Papon N., Courdavault V., Clastre M., Bennett R. J.. ( 2013;). Emerging and emerged pathogenic Candida species: beyond the Candida albicans paradigm. . PLoS Pathog 9:, e1003550. [CrossRef] [PubMed]
    [Google Scholar]
  21. Paul S., Bair T. B., Moye-Rowley W. S.. ( 2014;). Identification of genomic binding sites for Candida glabrata Pdr1 transcription factor in wild-type and ρ0 cells. . Antimicrob Agents Chemother 58:, 6904–6912 [CrossRef] [PubMed]
    [Google Scholar]
  22. Pfaller M. A., Diekema D. J.. ( 2007;). Epidemiology of invasive candidiasis: a persistent public health problem. . Clin Microbiol Rev 20:, 133–163 [CrossRef] [PubMed]
    [Google Scholar]
  23. Pfaller M. A., Diekema D. J.. ( 2010;). Epidemiology of invasive mycoses in North America. . Crit Rev Microbiol 36:, 1–53 [CrossRef] [PubMed]
    [Google Scholar]
  24. Pfaller M. A., Messer S. A., Boyken L., Huynh H., Hollis R. J., Diekema D. J.. ( 2002;). In vitro activities of 5-fluorocytosine against 8,803 clinical isolates of Candida spp.: global assessment of primary resistance using National Committee for Clinical Laboratory Standards susceptibility testing methods. . Antimicrob Agents Chemother 46:, 3518–3521 [CrossRef] [PubMed]
    [Google Scholar]
  25. Pfaller M. A., Diekema D. J., Gibbs D. L., Newell V. A., Ellis D., Tullio V., Rodloff A., Fu W., Ling T. A.. ( 2010;). Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: a 10.5-year analysis of susceptibilities of Candida species to fluconazole and voriconazole as determined by CLSI standardized disk diffusion. . J Clin Microbiol 48:, 1366–1377 [CrossRef] [PubMed]
    [Google Scholar]
  26. Pfaller M. A., Messer S. A., Woosley L. N., Jones R. N., Castanheira M.. ( 2013;). Echinocandin and triazole antifungal susceptibility profiles for clinical opportunistic yeast and mold isolates collected from 2010 to 2011: application of new CLSI clinical breakpoints and epidemiological cutoff values for characterization of geographic and temporal trends of antifungal resistance. . J Clin Microbiol 51:, 2571–2581 [CrossRef] [PubMed]
    [Google Scholar]
  27. Praz˙yńska M., Gospodarek E.. ( 2014;). In vitro effect of amphotericin B on Candida albicans, Candida glabrata and Candida parapsilosis biofilm formation. . Mycopathologia 177:, 19–27 [CrossRef] [PubMed]
    [Google Scholar]
  28. Rodrigues C. F., Silva S., Henriques M.. ( 2014;). Candida glabrata: a review of its features and resistance. . Eur J Clin Microbiol Infect Dis 33:, 673–688 [CrossRef] [PubMed]
    [Google Scholar]
  29. Sanglard D., Ischer F., Calabrese D., Majcherczyk P. A., Bille J.. ( 1999;). The ATP binding cassette transporter gene CgCDR1 from Candida glabrata is involved in the resistance of clinical isolates to azole antifungal agents. . Antimicrob Agents Chemother 43:, 2753–2765 [PubMed]
    [Google Scholar]
  30. Sanglard D., Ischer F., Bille J.. ( 2001;). Role of ATP-binding-cassette transporter genes in high-frequency acquisition of resistance to azole antifungals in Candida glabrata. . Antimicrob Agents Chemother 45:, 1174–1183 [CrossRef] [PubMed]
    [Google Scholar]
  31. Sanguinetti M., Posteraro B., Fiori B., Ranno S., Torelli R., Fadda G.. ( 2005;). Mechanisms of azole resistance in clinical isolates of Candida glabrata collected during a hospital survey of antifungal resistance. . Antimicrob Agents Chemother 49:, 668–679 [CrossRef] [PubMed]
    [Google Scholar]
  32. Santhanam J., Nazmiah N., Aziz M. N.. ( 2013;). Species distribution and antifungal susceptibility patterns of Candida species: is low susceptibility to itraconazole a trend in Malaysia?. Med J Malaysia 68:, 343–347 [PubMed]
    [Google Scholar]
  33. Silva S., Negri M., Henriques M., Oliveira R., Williams D. W., Azeredo J.. ( 2012;). Candida glabrata, Candida parapsilosis and Candida tropicalis: biology, epidemiology, pathogenicity and antifungal resistance. . FEMS Microbiol Rev 36:, 288–305 [CrossRef] [PubMed]
    [Google Scholar]
  34. Szweda P., Gucwa K., Naumiuk L., Romanowska E., Dzierzanowska- Fangrat K., Brillowska-Dabrowska A., Wojciechowska-Koszko I., Milewski S.. ( 2014;). Evaluation of possibilities in identification and susceptibility testing for Candida glabrata clinical isolates with the Integral System Yeast Plus (ISYP). . Acta Microbiol Immunol Hung 61:, 161–172 [CrossRef] [PubMed]
    [Google Scholar]
  35. Tscherner M., Schwarzmüller T., Kuchler K.. ( 2011;). Pathogenesis and antifungal drug resistance of the human fungal pathogen Candida glabrata. . Pharmaceuticals 4:, 169–186 [CrossRef]
    [Google Scholar]
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