Dataset Information

Insight into the role of HOG pathway components Ssk2p, Pbs2p, and Hog1p in the opportunistic yeast Candida lusitaniae.

ABSTRACT: In the present study, we have investigated the role of SSK2, PBS2, and HOG1, encoding modules of the high-osmolarity-glycerol mitogen-activated protein kinase pathway in Candida lusitaniae. Functional analysis of mutants indicated that Ssk2p, Pbs2p, and Hog1p are involved in osmotolerance, drug sensitivity, and heavy metal tolerance but not in oxidant stress adaptation.

SUBMITTER: Boisnard S

PROVIDER: S-EPMC2593183 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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Insight into the role of HOG pathway components Ssk2p, Pbs2p, and Hog1p in the opportunistic yeast Candida lusitaniae.

Boisnard Stéphanie S Ruprich-Robert Gwenaël G Florent Martine M Da Silva Bruno B Chapeland-Leclerc Florence F Papon Nicolas N

Eukaryotic cell 20081024 12

In the present study, we have investigated the role of SSK2, PBS2, and HOG1, encoding modules of the high-osmolarity-glycerol mitogen-activated protein kinase pathway in Candida lusitaniae. Functional analysis of mutants indicated that Ssk2p, Pbs2p, and Hog1p are involved in osmotolerance, drug sensitivity, and heavy metal tolerance but not in oxidant stress adaptation. ...[more]

PMID: 18952902

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Project description:OBJECTIVES:Candida lusitaniae is an opportunistic yeast pathogen in certain high-risk patient populations/cohorts. The species exhibits an unusual antifungal susceptibility profile with tendency to acquire rapid resistance. Here, we describe prevalence of C. lusitaniae in clinical specimens in Kuwait, its antifungal susceptibility profile and role in neonatal fungemia. METHODS:Clinical C. lusitaniae isolates recovered from diverse specimens during 2011 to 2017 were retrospectively analyzed. All isolates were identified by germ tube test, growth on CHROMagar Candida and by Vitek 2 yeast identification system. A simple species-specific PCR assay was developed and results were confirmed by PCR-sequencing of ITS region of rDNA. Antifungal susceptibility was determined by Etest. Minimum inhibitory concentrations (MICs) were recorded after 24 h incubation at 35°C. RESULTS:Of 7068 yeast isolates, 134 (1.89%) were identified as C. lusitaniae including 25 (2.52%) among 990 bloodstream isolates. Species-specific PCR and PCR-sequencing of rDNA confirmed identification. Of 11 cases of neonatal candidemia, 9 occurred in NICU of Hospital A and are described here. Eight of 9 neonates received liposomal amphotericin B, which was followed by fluconazole in 7 and additionally by caspofungin in 2 cases as salvage therapy. Three of 8 (37.5%) patients died. No isolate exhibited reduced susceptibility to amphotericin B, fluconazole, voriconazole, caspopfungin, micafungin and anidulafungin. The MIC ± geometric mean values for amphotericin B, fluconazole, voriconazole, and caspofungin were as follows: 0.072 ± 0.037 ?g/ml, 2.32 ± 0.49 ?g/ml, 0.09 ± 0.01 ?g/ml and 0.16 ± 0.08 ?g/ml, respectively. Only two isolates exhibited reduced susceptibility to fluconazole. CONCLUSIONS:This study describes the prevalence and antifungal susceptibility profile of clinical C. lusitaniae isolates in Kuwait. No isolate showed reduced susceptibility to amphotericin B. The study highlights the emerging role of C. lusitaniae as a healthcare-associated pathogen capable of causing fungemia in preterm neonates and causing significant mortality.

Project description:BACKGROUND:Opportunistic yeast pathogens of the genus Candida are an important medical problem. Candida albicans, the most prevalent Candida species, is a natural commensal of humans that can adopt a pathogenic behavior. This species is highly heterozygous and cannot undergo meiosis, adopting instead a parasexual cycle that increases genetic variability and potentially leads to advantages under stress conditions. However, the origin of C. albicans heterozygosity is unknown, and we hypothesize that it could result from ancestral hybridization. We tested this idea by analyzing available genomes of C. albicans isolates and comparing them to those of hybrid and non-hybrid strains of other Candida species. RESULTS:Our results show compelling evidence that C. albicans is an evolved hybrid. The genomic patterns observed in C. albicans are similar to those of other hybrids such as Candida orthopsilosis MCO456 and Candida inconspicua, suggesting that it also descends from a hybrid of two divergent lineages. Our analysis indicates that most of the divergence between haplotypes in C. albicans heterozygous blocks was already present in a putative heterozygous ancestor, with an estimated 2.8% divergence between homeologous chromosomes. The levels and patterns of ancestral heterozygosity found cannot be fully explained under the paradigm of vertical evolution and are not consistent with continuous gene flux arising from lineage-specific events of admixture. CONCLUSIONS:Although the inferred level of sequence divergence between the putative parental lineages (2.8%) is not clearly beyond current species boundaries in Saccharomycotina, we show here that all analyzed C. albicans strains derive from a single hybrid ancestor and diverged by extensive loss of heterozygosity. This finding has important implications for our understanding of C. albicans evolution, including the loss of the sexual cycle, the origin of the association with humans, and the evolution of virulence traits.

Dataset Information

Insight into the role of HOG pathway components Ssk2p, Pbs2p, and Hog1p in the opportunistic yeast Candida lusitaniae.

Publications

Insight into the role of HOG pathway components Ssk2p, Pbs2p, and Hog1p in the opportunistic yeast Candida lusitaniae.

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