Genome‐wide gene expression profiling and a forward genetic screen show that differential expression of the sodium ion transporter Ena21 contributes to the differential tolerance of <i>Candida albicans</i> and <i>Candida dubliniensis</i> to osmotic stress

Enjalbert, Brice; Moran, Gary P.; Vaughan, Claire; Yeomans, Tim; MacCallum, Donna M.; Quinn, Janet; Coleman, David C.; Brown, Alistair J. P.; Sullivan, Derek J.

doi:10.1111/j.1365-2958.2009.06640.x

Cited by 38 publications

(32 citation statements)

References 42 publications

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“…Similar to SOD, catalase activity was signifi cantly (p < 0.01) higher in the sensitive and resistant C. albicans strains compared to the respective C. dubliniensis groups. In combination with the increased susceptibility of C. dubliniensis to hydrogen peroxide and macrophage killing, this result suggests that C. albicans is better protected from oxidative stress than C. dubliniensis, in accordance with the higher virulence of C. albicans 33,34,35 .…”

Section: Discussionsupporting

confidence: 59%

Fluconazole and amphotericin-B resistance are associated with increased catalase and superoxide dismutase activity in Candida albicans and Candida dubliniensis

Linares

Giacomelli

Altenhofen

et al. 2013

Rev. Soc. Bras. Med. Trop.

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Introduction:Candida dubliniensis, a new species of Candida that has been recovered from several sites in healthy people, has been associated with recurrent episodes of oral candidiasis in AIDS and HIV-positive patients. This species is closely related to C. albicans. The enzymatic activity of C. dubliniensis in response to oxidative stress is of interest for the development of drugs to combat C. dubliniensis. Methods: Fluconazole-and amphotericin B-resistant strains were generated as described by FeketeForgács et al. (2000). Superoxide dismutase (SOD) and catalase assays were performed as described by McCord and Fridovich (1969) and Aebi (1984), respectively. Results: We demonstrated that superoxide dismutase (SOD) and cata lase activities were signifi cantly higher (p<0.05) in the fl uconazole-and amphotericin B-resistant strains of C. dubliniensis and C. albicans than in the sensitive strains. The catalase and SOD activities were also signifi cantly (p<0.01) higher in the sensitive and resistant C. albicans strains than in the respective C. dubliniensis strains. Conclusions: These data suggest that C. albicans is better protected from oxidative stress than C. dubliniensis and that fl uconazole, like amphotericin B, can induce oxidative stress in Candida; oxidative stress induces an adaptive response that results in a coordinated increase in catalase and SOD activities.

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Section: Discussionsupporting

confidence: 59%

Fluconazole and amphotericin-B resistance are associated with increased catalase and superoxide dismutase activity in Candida albicans and Candida dubliniensis

Linares

Giacomelli

Altenhofen

et al. 2013

Rev. Soc. Bras. Med. Trop.

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“…These observations suggest a general role for calcineurin in controlling Ca 2ϩ homeostasis. Recently, Enjalbert et al showed that C. dubliniensis is Na ϩ hypersensitive compared with C. albicans (31). Thus, it is of interest to investigate the potential roles of calcineurin in Na ϩ , Ca 2ϩ , and Mn 2ϩ homeostasis in C. dubliniensis.…”

Section: Resultsmentioning

confidence: 99%

Calcineurin Controls Drug Tolerance, Hyphal Growth, and Virulence in Candida dubliniensis

et al. 2011

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Candida dubliniensis is an emerging pathogenic yeast species closely related to Candida albicans and frequently found colonizing or infecting the oral cavities of HIV/AIDS patients. Drug resistance during C. dubliniensis infection is common and constitutes a significant therapeutic challenge. The calcineurin inhibitor FK506 exhibits synergistic fungicidal activity with azoles or echinocandins in the fungal pathogens C. albicans, Cryptococcus neoformans, and Aspergillus fumigatus. In this study, we show that calcineurin is required for cell wall integrity and wild-type tolerance of C. dubliniensis to azoles and echinocandins; hence, these drugs are candidates for combination therapy with calcineurin inhibitors. In contrast to C. albicans, in which the roles of calcineurin and Crz1 in hyphal growth are unclear, here we show that calcineurin and Crz1 play a clearly demonstrable role in hyphal growth in response to nutrient limitation in C. dubliniensis. We further demonstrate that thigmotropism is controlled by Crz1, but not calcineurin, in C. dubliniensis. Similar to C. albicans, C. dubliniensis calcineurin enhances survival in serum. C. dubliniensis calcineurin and crz1/crz1 mutants exhibit attenuated virulence in a murine systemic infection model, likely attributable to defects in cell wall integrity, hyphal growth, and serum survival. Furthermore, we show that C. dubliniensis calcineurin mutants are unable to establish murine ocular infection or form biofilms in a rat denture model. That calcineurin is required for drug tolerance and virulence makes fungus-specific calcineurin inhibitors attractive candidates for combination therapy with azoles or echinocandins against emerging C. dubliniensis infections.

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“…Analysis of Wor1 (246) and Ste2 (271) supports the hypothesis that switching emerged in the ancestor of C. albicans and C. dubliniensis. It is not clear whether this ancestor was highly pathogenic (like C. albicans) or relatively attenuated (like C. dubliniensis), although recent evidence suggests that lack of pathogenesis in C. dubliniensis may result from gene loss or changes in regulatory pathways (66,117,184). White-opaque switching is not needed for pathogenesis in C. tropicalis and C. parapsilosis, which presumably also have a long association with the human host.…”

Section: Saccharomyces Cerevisiae and Candida Glabratamentioning

confidence: 95%

Fungal Sex and Pathogenesis

Butler

2010

Clin Microbiol Rev

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SUMMARYHuman fungal pathogens are associated with diseases ranging from dandruff and skin colonization to invasive bloodstream infections. The major human pathogens belong to theCandida,Aspergillus, andCryptococcusclades, and infections have high and increasing morbidity and mortality. Many human fungal pathogens were originally assumed to be asexual. However, recent advances in genome sequencing, which revealed that many species have retained the genes required for the sexual machinery, have dramatically influenced our understanding of the biology of these organisms. Predictions of a rare or cryptic sexual cycle have been supported experimentally for some species. Here, I examine the evidence that human pathogens reproduce sexually. The evolution of the mating-type locus in ascomycetes (includingCandidaandAspergillusspecies) and basidiomycetes (MalasseziaandCryptococcus) is discussed. I provide an overview of how sex is suppressed in different species and discuss the potential associations with pathogenesis.

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Genome‐wide gene expression profiling and a forward genetic screen show that differential expression of the sodium ion transporter Ena21 contributes to the differential tolerance of Candida albicans and Candida dubliniensis to osmotic stress

Cited by 38 publications

References 42 publications

Fluconazole and amphotericin-B resistance are associated with increased catalase and superoxide dismutase activity in Candida albicans and Candida dubliniensis

Fluconazole and amphotericin-B resistance are associated with increased catalase and superoxide dismutase activity in Candida albicans and Candida dubliniensis

Calcineurin Controls Drug Tolerance, Hyphal Growth, and Virulence in Candida dubliniensis

Fungal Sex and Pathogenesis

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