MOLECULAR CHARACTERIZATION OF AZOLE RESISTANCE MECHANISMS IN CANDIDA ALBICANS CLINICAL ISOLATES FROM HIV-INFECTED PATIENTS IN INDIAAbstract
Candida albicans has been the most widely premeditated pathogen in antifungal resistance because of their morbidity and mortality allied with infections in immunocompromised patients. A variety of mechanisms of resistance exist, with the most significant being those due to efflux pumps. The emergence of resistance during therapy in other settings appears uncommon but has been described in settings other than HIV-infected patients. We studied azole-resistant mechanism in 20 isolates of Candida albicans from HIV infected patients; these mechanisms include the presence of point mutations in the ERG11 gene and several genes encoding efflux pumps. Using Northern blot analyses, the expression patterns of these genes have been determined during logarithmic and stationary phases of cell growth. Point Mutations and overexpression of ERG11, and several genes encoding efflux pumps, as measured by quantitative real-time reverse transcriptase polymerase chain reaction in 20 clinical isolates of itraconazole resistant C. albicans strains. CDR1, CDR2, and MDR1 are expressed early on during logarithmic growth, CDR4 is expressed late during logarithmic growth, and CDR1 is preferentially expressed in stationary-phase cells. MDR1 and CDR mRNAs is transcriptionally overexpressed in the resistant isolate, suggesting that the antifungal drug resistance in this series is associated with the promoter and trans-acting factors of the CDR1, CDR2, and MDR1 genes, while increased mRNA levels of efflux pump genes are commonly associated with azole resistance.
D. D. Singh, M. Khare and V. Singh*
Department of Microbiology, Barkatullah University, Bhopal, Madhya Pradesh, India.
15 March 2014
25 April 2014
28 June 2014
01 September 2014