Multidrug Transporters and Alterations in Sterol Biosynthesis Contribute to Azole Antifungal Resistance in Candida parapsilosis

Berkow, Elizabeth L.; Manigaba, Kayihura; Parker, Josie E.; Barker, Katherine S.; Kelly, S. L.; Rogers, P. David

doi:10.1128/aac.01358-15

Cited by 83 publications

(121 citation statements)

References 26 publications

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“…In another study, 35 unrelated fluconazole-resistant and four unrelated susceptible isolates of C. parapsilosis were examined to elucidate mechanisms of fluconazole resistance in C. parapsilosis (Berkow et al, 2015). Sixteen resistant isolates overexpressed CDR1 , three other resistant isolates exhibited MDR1 overexpression, and eight resistant isolates demonstrated overexpression of ERG11 as compared to the susceptible isolates.…”

Section: Azole Antifungal Resistance Mechanismsmentioning

confidence: 99%

Azole Antifungal Resistance in Candida albicans and Emerging Non-albicans Candida Species

et al. 2017

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Within the limited antifungal armamentarium, the azole antifungals are the most frequent class used to treat Candida infections. Azole antifungals such as fluconazole are often preferred treatment for many Candida infections as they are inexpensive, exhibit limited toxicity, and are available for oral administration. There is, however, extensive documentation of intrinsic and developed resistance to azole antifungals among several Candida species. As the frequency of azole resistant Candida isolates in the clinical setting increases, it is essential to elucidate the mechanisms of such resistance in order to both preserve and improve upon the azole class of antifungals for the treatment of Candida infections. This review examines azole resistance in infections caused by C. albicans as well as the emerging non-albicans Candida species C. parapsilosis, C. tropicalis, C. krusei, and C. glabrata and in particular, describes the current understanding of molecular basis of azole resistance in these fungal species.

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Section: Azole Antifungal Resistance Mechanismsmentioning

confidence: 99%

Azole Antifungal Resistance in Candida albicans and Emerging Non-albicans Candida Species

et al. 2017

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“…During recent years, advances have been achieved in terms of understanding the molecular bases of decreased antifungal drug susceptibility. For example, alterations in ergosterol biosynthetic mechanisms and upregulation of multidrug transporters in the cell wall are the two most common pathways of development of azole resistance (281)(282)(283). In C. albicans, three major regulators are commonly highlighted to regulate azole resistance, two multidrug transporters (Cdr1 and Mdr1) and an enzyme involved in ergosterol biosynthesis (Erg11), as all three are overexpressed in the presence of azole derivates.…”

Section: Antifungal Susceptibility and Resistancementioning

confidence: 99%

Candida parapsilosis: from Genes to the Bedside

et al. 2019

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SUMMARY Patients with suppressed immunity are at the highest risk for hospital-acquired infections. Among these, invasive candidiasis is the most prevalent systemic fungal nosocomial infection. Over recent decades, the combined prevalence of non-albicans Candida species outranked Candida albicans infections in several geographical regions worldwide, highlighting the need to understand their pathobiology in order to develop effective treatment and to prevent future outbreaks. Candida parapsilosis is the second or third most frequently isolated Candida species from patients. Besides being highly prevalent, its biology differs markedly from that of C. albicans, which may be associated with C. parapsilosis’ increased incidence. Differences in virulence, regulatory and antifungal drug resistance mechanisms, and the patient groups at risk indicate that conclusions drawn from C. albicans pathobiology cannot be simply extrapolated to C. parapsilosis. Such species-specific characteristics may also influence their recognition and elimination by the host and the efficacy of antifungal drugs. Due to the availability of high-throughput, state-of-the-art experimental tools and molecular genetic methods adapted to C. parapsilosis, genome and transcriptome studies are now available that greatly contribute to our understanding of what makes this species a threat. In this review, we summarize 10 years of findings on C. parapsilosis pathogenesis, including the species’ genetic properties, transcriptome studies, host responses, and molecular mechanisms of virulence. Antifungal susceptibility studies and clinician perspectives are discussed. We also present regional incidence reports in order to provide an updated worldwide epidemiology summary.

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“…As shown by other authors, the development of azole resistance in Candida spp. classically involves different mechanisms, such as the activation of transcription factors, up‐regulation or mutation of genes associated with ergosterol biosynthesis (ERG3 and ERG11), and up‐regulation of genes encoding efflux pumps (CDR1, CDR2 and MDR1) . To fully elucidate the mechanisms underlying azole resistance in animal strains of C. albicans , further investigations are required to assess the role of ERG11 polymorphisms/mutations and transcription factors (UPC2, TAC1 and MRR1) in this phenomenon.…”

Section: Discussionmentioning

confidence: 99%

Azole resistance inCandida albicansfrom animals: Highlights on efflux pump activity and gene overexpression

Rocha

Bandeira

Alencar

et al. 2017

Mycoses

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This study investigated potential mechanisms of azole resistance among Candida albicans from animals, including efflux pump activity, ergosterol content and gene expression. For this purpose, 30 azole-resistant C. albicans strains from animals were tested for their antifungal susceptibility, according to document M27-A3, efflux pump activity by rhodamine 6G test, ergosterol content and expression of the genes CDR1, CDR2, MDR1, ERG11 by RT-qPCR. These strains were resistant to at least one azole derivative. Resistance to fluconazole and itraconazole was detected in 23 and 26 strains respectively. Rhodamine 6G tests showed increased activity of efflux pumps in the resistant strains, showing a possible resistance mechanism. There was no difference in ergosterol content between resistant and susceptible strains, even after fluconazole exposure. From 30 strains, 22 (73.3%) resistant animal strains overexpressed one or more genes. From this group, 40.9% (9/22) overexpressed CDR1, 18.2% (4/22) overexpressed CDR2, 59.1% (13/22) overexpressed MDR1 and 54.5% (12/22) overexpressed ERG11. Concerning gene expression, a positive correlation was observed only between CDR1 and CDR2. Thus, azole resistance in C. albicans strains from animals is a multifactorial process that involves increased efflux pump activity and the overexpression of different genes.

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Multidrug Transporters and Alterations in Sterol Biosynthesis Contribute to Azole Antifungal Resistance in Candida parapsilosis

Cited by 83 publications

References 26 publications

Azole Antifungal Resistance in Candida albicans and Emerging Non-albicans Candida Species

Azole Antifungal Resistance in Candida albicans and Emerging Non-albicans Candida Species

Candida parapsilosis: from Genes to the Bedside

Azole resistance inCandida albicansfrom animals: Highlights on efflux pump activity and gene overexpression

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