Structure and regulation of the HSP90 gene from the pathogenic fungus Candida albicans

Swoboda, Rolf; Bertram, Gwyneth; Budge, Susan; Gooday, Graham W.; Gow, Neil A. R.; Brown, Alistair J. P.

doi:10.1128/iai.63.11.4506-4514.1995

Cited by 80 publications

(28 citation statements)

References 54 publications

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“…Nevertheless, it has also been shown that human peripheral blood lymphocytes are capable of inducing the production of immunoglobulins against invasive Candida species to promote fungal clearance (362). During investigations of such responses, antibodies specific to the carboxyl fragment of C. albicans heat shock protein 90 (HSP90) have been identified (363,364). The level of such antibodies was shown to correlate with disease outcome (365,366).…”

Section: Host Immune Responsesmentioning

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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Section: Host Immune Responsesmentioning

confidence: 99%

Candida parapsilosis: from Genes to the Bedside

et al. 2019

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“…Under the category of probes used, CDR1 and CDR2 amplicons, generated through PCR using primers KM1/KM2 and CDR2L/CDR2R, respectively (listed in Table 3), were used as specific probes for the two genes. A 4.7 kb PvuII fragment from pPDR3.3, and a 2.2 kb fragment from ApaI-SmaI of pHSP90 1/2/2 (Swoboda et al, 1995) were used for steroid-induced transcript profiling of PDR5 and HSP90 , respectively. The ACT1 mRNA was analysed using a 1.6 kb BamHI-Hind III fragment from pACT1.…”

Section: Rna Isolation and Northern Hybridizationmentioning

confidence: 99%

SRE1 and SRE2 are two specific steroid‐responsive modules of Candida drug resistance gene 1 (CDR1) promoter

Karnani

Gaur

Jha

et al. 2004

Yeast

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CDR1 gene encoding an ATP-driven drug extrusion pump has been implicated in the development of azole-resistance in Candida albicans. Although the upregulation of CDR1 expression by various environmental factors has been documented, the molecular mechanism underlying such process is poorly understood. We have demonstrated earlier that the CDR1 promoter encompasses a large number of cisregulatory elements, presumably mediating its response to various drugs. In this study we have identified a novel steroid responsive region (SRR) conferring β-oestradiol and progesterone inducibility on the CDR1 promoter. The SRR is located −696 to −521 bp upstream of the transcription start site; it is modular in nature and can confer steroid responsiveness to a heterologous promoter (ADH1 ) linked to a GFP reporter gene. In vitro DNase I protection analyses of SRR revealed two progesterone responsive sequences (−628 to −594 and −683 to −648) and one β-oestradiol responsive sequence (−628 to −577), which was further corroborated by the gel mobility shift assay. Deletion analyses within the SRR further delimited these steroid responsive sequences into two distinct elements, viz. SRE1 and SRE2. While SRE1 (−677 to −648) responds only to progesterone, SRE2 (−628 to −598) responded to both progesterone and β-oestradiol. Both SRE1 and SRE2 were specific for steroids, as they did not respond to other drugs, such as cycloheximide, miconazole and terbinafine. In silico comparison of the SRE1/2 with the promoter sequences of other MDR (CDR2 and PDR5 ) and non-MDR (HSP90 ) steroid-responsive genes revealed a similarity with respect to conservation of three 5 bp stretches (AAGAA, CCGAA and ATTGG). Taken together, we have identified a novel steroid responsive cisregulatory sequence in the CDR1 promoter, which presumably can be instrumental in understanding the steroid response cascade in Candida albicans.

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“…In Saccharomyces cerevisiae, the mRNA levels of ssa1 and ssa2 (cytosolic constitutive hsp70 homologues) increases during growth until the diauxic shift and then decreases [31]. In the yeast Candida albicans, the constitutive level of hsp90 mRNA increases transiently in the middle of exponential growth [32]. Apparently, the presence of constitutive HSCs is necessary for normal growth, as shown with hsp70 mutants in S. cerevisiae or with HSF mutants in Schizosaccharomyces pombe (review: [12]).…”

Section: Vegetative Hyphaementioning

confidence: 99%

Differential stress gene expression during the development of Neurospora crassa and other fungi

Rensing

1998

FEMS Microbiology Letters

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Stress genes are differentially expressed during the development of Neurospora crassa and other fungi. Large amounts of constitutive heat shock protein 70 (HSC70) are found in dormant conidia of N. crassa, whereas little mRNA of the related glucose-regulated protein (grp78) is detected. It is, however, not generally clear whether heat shock protein or mRNA is preferentially stored in dormant spores. Germinating spores of N. crassa increase the level of grp mRNA. During this developmental stage, the induction of inducible heat shock protein (hsp) genes can be elicited by heat shock only at certain times after the beginning of germination. Exponential growth (proliferation) is paralleled by increased levels of HSCs. The stationary state is characterized by decreased levels of some HSCs and increased levels of others. Conidiation in N. crassa is accompanied by a strong enhancement of the synthesis and levels of HSCs but also of HSPs after heat shock. This increase may serve a need for additional rounds of replication, for the expression and transport of sporulation-specific proteins or for stabilization of macromolecules in the spores and their preservation for germination. The control mechanisms involved in the differential expression of hsc genes are currently not known. z

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Structure and regulation of the HSP90 gene from the pathogenic fungus Candida albicans

Cited by 80 publications

References 54 publications

Candida parapsilosis: from Genes to the Bedside

Candida parapsilosis: from Genes to the Bedside

SRE1 and SRE2 are two specific steroid‐responsive modules of Candida drug resistance gene 1 (CDR1) promoter

Differential stress gene expression during the development of Neurospora crassa and other fungi

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