Fluconazole-resistant recurrent oral candidiasis in human immunodeficiency virus-positive patients: persistence of Candida albicans strains with the same genotype

Millon, Laurence; Manteaux, A.; Reboux, Gabriel; Drobacheff, C.; Monod, Michel; Barale, T; Michel-Briand, Y

doi:10.1128/jcm.32.4.1115-1118.1994

Cited by 189 publications

(73 citation statements)

References 27 publications

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“…Genomic DNA from C. albicans strains was isolated as described previously (Millon et al, 1994). Southern hybridization with enhanced chemiluminescence-labelled probes was performed with the ECL labelling and detection kit provided by Amersham (Braunschweig, Germany) according to the instructions of the manufacturer.…”

Section: Southern and Northern Hybridizationmentioning

confidence: 99%

The Mep2p ammonium permease controls nitrogen starvation‐induced filamentous growth in Candida albicans

Biswas

Morschhäuser

2005

Molecular Microbiology

173

169

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SummaryNitrogen starvation is one of the signals that induce Candida albicans , the major fungal pathogen of humans, to switch from yeast to filamentous growth. In response to nitrogen starvation, C. albicans expresses the MEP1 and MEP2 genes, which encode two ammonium permeases that enable growth when limiting concentrations of ammonium are the only available nitrogen source. In addition to its role as an ammonium transporter, Mep2p, but not Mep1p, also has a central function in the induction of filamentous growth on a solid surface under limiting nitrogen conditions. When ammonium is absent or present at low concentrations, Mep2p activates both the Cph1p-dependent mitogen-activated protein (MAP) kinase pathway and the cAMP-dependent signalling pathway in a Ras1p-dependent fashion via its C-terminal cytoplasmic tail, which is essential for signalling but dispensable for ammonium transport. In contrast, under ammonium-replete conditions that require transporter-mediated uptake Mep2p is engaged in ammonium transport and signalling is blocked such that C. albicans continues to grow in the budding yeast form. Mep2p is a less efficient ammonium transporter than Mep1p and is expressed at much higher levels, a distinguishing feature that is important for its signalling function. At sufficiently high concentrations, ammonium represses filamentous growth even when the signalling pathways are artificially activated. Therefore, C. albicans has established a regulatory circuit in which a preferred nitrogen source, ammonium, also serves as an inhibitor of morphogenesis that is taken up into the cell by the same transporter that mediates the induction of filamentous growth in response to nitrogen starvation.

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Section: Southern and Northern Hybridizationmentioning

confidence: 99%

The Mep2p ammonium permease controls nitrogen starvation‐induced filamentous growth in Candida albicans

Biswas

Morschhäuser

2005

Molecular Microbiology

173

169

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“…Genomic DNA from C. albicans was isolated as described previously (Millon et al, 1994). DNA (10 µg) was digested with EcoRI, separated on a 1% agarose gel and, after ethidium bromide staining, transferred by vacuum blotting onto a nylon membrane and fixed by UV cross-linking.…”

Section: Isolation Of Genomic Dna and Southern Hybridizationmentioning

confidence: 99%

Candida albicans MTLα tup1Δ mutants can reversibly switch to mating‐competent, filamentous growth forms

Park

Morschhäuser

2005

Molecular Microbiology

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SummaryCandida albicans strains that are homozygous at the mating type locus ( MTLa or MTL α α α α ) can spontaneously switch from the normal round-to-oval yeast cell morphology to an elongated, so-called opaque cell form that can mate with opaque cells of the opposite mating type. In response to environmental signals, C. albicans also undergoes a transition from yeast to filamentous growth, which is negatively regulated by the general repressor Tup1p. Therefore, C. albicans mutants in which the TUP1 gene is inactivated grow constitutively in the filamentous form. We found that tup1 ∆ ∆ ∆ ∆ mutants of the MTL α α α α strain WO-1 are still able to undergo phenotypic switching. Although the mutants had lost the capacity to grow in the normal yeast (white) or opaque forms, they could still reversibly switch between four different cell and colony phenotypes (designated as fuzzy, frizzy, wrinkled and smooth) at a frequency of about 10 − − − − 3 to 10. Deletion of TUP1 resulted in deregulated expression of phasespecific genes. While the white-specific WH11 gene was constitutively expressed in all four cell types, the opaque-specific SAP1 gene remained repressed and the opaque-specific OP4 gene was weakly induced in all phase variants. In spite of the loss of white-and opaque-specific cell morphology and gene expression, the tup1 ∆ ∆ ∆ ∆ mutants retained an important characteristic of their wild-type parent, the ability to switch to a mating-competent form. The three filamentous phase variants (fuzzy, frizzy and wrinkled) all were able to mate and produce recombinant progeny with opaque cells of an MTLa strain at frequencies that were somewhat lower than those of normal opaque cells, whereas the smooth phase variant was unable to do so. Therefore, although deletion of TUP1 in C. albicans MTL α α α α cells affects cellular morphology and gene expression patterns, the mutants can still reversibly switch between mating-competent andincompetent cell types and mate with a partner of the opposite mating type.

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“…Of these drugs, fluconazole has the most attractive pharmacodynamic profile with a low level of toxicity and a high degree of bioavailability, including the capacity to produce high concentrations of the active drug in saliva, cerebrospinal fluid and urine (16). Nevertheless, longterm prophylaxis with fluconazole, either intermittently or continuously, has resulted in an increasing number of patients with fluconazole-resistant candidiasis (6,(23)(24)(25)(26)(27)(28)(29). For instance, of HIV-infected patients with symptomatic candidiasis, 80-100% recover within 5-10 days of fluconazole therapy (2,4,6,10) although 20-100% of such patients relapse within a month once treatment is stopped (2,3,6,10).…”

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confidence: 99%

Heterogeneity in antifungal susceptibility of clones of Candida albicans isolated on single and sequential visits from a HIV‐infected southern Chinese cohort

Samaranayake

Tsang

et al. 2001

J Oral Pathology Medicine

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The increased frequency and severity of candidal infections in human immunodeficiency virus (HIV)-infected individuals has prompted the wide use of antifungals, such as amphotericin B, ketoconazole, and fluconazole, resulting in the emergence of drug-resistant strains of Candida albicans. To study this phenomenon in an ethnic Chinese cohort, we isolated multiple colonies of Candida from the oral cavities of 16 HIV-infected patients on single and subsequent sequential visits over a period of 12 months. Ten of the 16 patients had sporadic episodes of oropharyngeal candidiasis (Group A), while the remainder were asymptomatic with respect to this condition (Group B). Oral rinses were collected and immediately processed in the laboratory for the isolation of C. albicans in a standard manner. A total of 433 C. albicans isolates were tested for their susceptibility to amphotericin B, ketoconazole and fluconazole by an agar diffusion method using the commercially available E-test. All tested isolates demonstrated variable susceptibility to amphotericin B, ketoconazole and fluconazole. The minimum inhibitory concentration (MIC) of the isolates for amphotericin B, ketoconazole and fluconazole ranged from <0.002-1.5 microg/ml, <0.002-4.0 microg/ml and <0.016-32 microg/ml, respectively. Sequential isolates of a few patients demonstrated variable susceptibility to all the antifungals, and no discernible MIC pattern emerged either in group A or B over time. Interestingly, significant variation in antifungal susceptibility was also noted in isolates obtained from the same patient on a single visit. Sequential yeast isolates in 9 of 16 patients (56%) demonstrated significant differences in MIC within and between visits for both amphotericin B and ketoconazole, while a lower percentage--44%(7/16)--exhibited this trait for fluconazole. Our study demonstrates the diversity in antifungal susceptibility in either commensal or "infective" oral strains of C. albicans in HIV disease, and shows the need for vigilance for the emergence of resistant strains, and for frequent antifungal susceptibility studies.

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Fluconazole-resistant recurrent oral candidiasis in human immunodeficiency virus-positive patients: persistence of Candida albicans strains with the same genotype

Cited by 189 publications

References 27 publications

The Mep2p ammonium permease controls nitrogen starvation‐induced filamentous growth in Candida albicans

The Mep2p ammonium permease controls nitrogen starvation‐induced filamentous growth in Candida albicans

Candida albicans MTLα tup1Δ mutants can reversibly switch to mating‐competent, filamentous growth forms

Heterogeneity in antifungal susceptibility of clones of Candida albicans isolated on single and sequential visits from a HIV‐infected southern Chinese cohort

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