ERG11 Gene Mutations and MDR1 Upregulation Confer Pan-Azole Resistance in Candida tropicalis Causing Disseminated Candidiasis in an Acute Lymphoblastic Leukemia Patient on Posaconazole Prophylaxis
نویسندگان
چکیده
In this study, we present a rare case of fatal breakthrough Candida tropicalis infection in a patient with acute lymphoblastic leukemia (ALL) while on posaconazole prophylaxis. Then, we explore the mechanisms underlying azole resistance by focusing on enhanced efflux pumps and changes in the azole target enzyme Erg11p, which was encoded by the ERG11 gene. Our study demonstrates that Y132C substitution of Erg11p combined with MDR1 overexpression may be the pan-azole resistance mechanisms in Candida tropicalis.
منابع مشابه
Mechanisms of azole resistance in 52 clinical isolates of Candida tropicalis in China.
OBJECTIVES To explore the mechanisms underlying azole resistance in clinical isolates of Candida tropicalis collected in China by focusing on their efflux pumps, respiratory status and azole antifungal target enzyme. METHODS Fifty-two clinical isolates of C. tropicalis were collected from five hospitals in four provinces of China and antifungal susceptibility tests were performed. Rhodamine 6...
متن کاملActivity of Isavuconazole and Other Azoles against Candida Clinical Isolates and Yeast Model Systems with Known Azole Resistance Mechanisms.
Isavuconazole is a novel, broad-spectrum, antifungal azole. In order to evaluate its interactions with known azole resistance mechanisms, isavuconazole susceptibility among different yeast models and clinical isolates expressing characterized azole resistance mechanisms was tested and compared to those of fluconazole, itraconazole, posaconazole, and voriconazole. Saccharomyces cerevisiae expres...
متن کاملInvestigation of Mutations of ERG11 Gene in Fluconazole Resistant Strains of Candida Albicans Isolated From Patients With Volvovaginitis in West of Mazandaran
Background and Aims: Candida albicans as an opportunistic fungal pathogen in human is the cause of volvovaginitis candidiasis. Azole resistance is cinsiderable as worldwide problem in treatment of candidiasis. Azole resistance can occur through different mechanisms such as mutation in ERG11 gene. The aim of our study was evaluation of ERG11 gene mutations in fluconazole resistant islotes of C. ...
متن کاملRapid, transient fluconazole resistance in Candida albicans is associated with increased mRNA levels of CDR.
Fluconazole-resistant Candida albicans, a cause of recurrent oropharyngeal candidiasis in patients with human immunodeficiency virus infection, has recently emerged as a cause of candidiasis in patients receiving cancer chemotherapy and marrow transplantation (MT). In this study, we performed detailed molecular analyses of a series of C. albicans isolates from an MT patient who developed dissem...
متن کاملMUTATION IN HOTSPOT REGIONS OF THE ERG11 GENE AND FLUCONAZOLE RESISTANCE IN CLINICAL ISOLATES OF CANDIDA ALBICANS IN RASHT CITY
Background & Aims: Nowadays, the common use of azoles has led to increased resistance to azole among Candida albicans strains. Amino acid substitutions in azole target enzyme, ERG11p, is attributed to azole resistance in some clinical strains of Candida albicans. The aim of this study was to evaluate ERG11 gene mutations in fluconazole-resistant isolates of Candida albicans in Rasht. Materials...
متن کامل