Igor Bruzual

Publications (2)7.65 Total impact

• Article: An MDR1 promoter allele with higher promoter activity is common in clinically isolated strains of Candida albicans.

  Igor Bruzual, Carol A Kumamoto
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  ABSTRACT: In the opportunistic fungal pathogen Candida albicans, up-regulation of MDR1, encoding an efflux transporter, leads to increased resistance to the antifungal drug fluconazole. Antifungal resistance has been linked to several types of genetic change in C. albicans, including changes in genome structure, genetic alteration of the drug target, and overexpression of transporters. High-level over-expression of MDR1 is commonly mediated by mutation in a trans-acting factor, Mrr1p. This report describes a second mechanism that contributes to up-regulation of MDR1 expression. By analyzing the sequence of the MDR1 promoter region in fluconazole-resistant and fluconazole-susceptible strains, we identified sequence polymorphisms that defined two linkage groups, corresponding to the two alleles in the diploid genome. One of the alleles conferred higher MDR1 expression compared with the other allele. Strains in which both alleles were of the higher activity type were common in collections of clinically isolated strains while strains carrying only the less active allele were rare. As increased expression of MDR1 confers higher resistance to drugs, strains with the more active MDR1 promoter allele may grow or survive longer when exposed to drugs or other selective pressures, providing greater opportunity for mutations that confer high-level drug resistance to arise. Through this mechanism, higher activity alleles of the MDR1 promoter could promote the development of drug resistance.
  MGG Molecular & General Genetics 12/2011; 286(5-6):347-57. · 2.58 Impact Factor
• Article: Biofilm formation by fluconazole-resistant Candida albicans strains is inhibited by fluconazole.

  Igor Bruzual, Perry Riggle, Susan Hadley, Carol A Kumamoto
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  ABSTRACT: The fungal pathogen Candida albicans forms biofilms on implanted medical devices, resulting in infections with high mortality. Fully developed biofilms, which are adherent communities of microorganisms, characteristically exhibit high resistance to antimicrobial drugs, making treatment of device-associated infection problematic. The aim of this study was to determine the effect of the addition of the azole antifungal fluconazole on the initiation of biofilm formation by both drug-susceptible and drug-resistant C. albicans strains. Our data reported here show that biofilm formation by both fluconazole-susceptible and fluconazole-resistant C. albicans strains was inhibited when fluconazole was present. For the fluconazole-susceptible strains, inhibition of growth due to the presence of the antifungal drug probably prevented the acquisition of high-level fluconazole resistance. However, for fluconazole-resistant strains, the inhibition of biofilm development was unexpected. Unexpectedly, fluconazole inhibited biofilm formation by a variety of laboratory isolated and clinically isolated fluconazole-resistant strains.
  Journal of Antimicrobial Chemotherapy 04/2007; 59(3):441-50. · 5.07 Impact Factor