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The incidence of fungal infections is increasing at an alarming rate and has posed a great challenge for science in recent years. The rise in these infections has been related to the increase in immunocompromised patients and the resistance of different species to antifungal drugs. Infections caused by the different Candida species, especially Candida albicans, are one of the most common mycoses in humans, and the etiological agents are considered opportunistic pathogens associated with high mortality rates when disseminated infections occur. Candida lusitaniae is considered an emerging opportunistic pathogen that most frequently affects immunocompromised patients with some comorbidity. Although it is a low-frequency pathogen, and the mortality rate of C. lusitaniae-caused candidemia does not exceed 5%, some isolates are known to be resistant to antifungals such as amphotericin B, 5-fluorocytosine, and fluconazole. In this paper, a detailed review of the current literature on this organism and its different aspects, such as its biology, possible virulence factors, pathogen-host interaction, diagnosis, and treatment of infection, is provided. Of particular interest, through Blastp analysis we predicted possible virulence factors in this species. [ABSTRACT FROM AUTHOR]

With the help of an automatic protein sequenator, we have verified a prediction made by us in a recent paper, namely that residue 16 in Candida krusei cytochrome c is a glutamine and not a glutamic acid. Neurospora crassa cytochrome c now remains the only mitochondrial cytochrome c which apparently does not have a glutamine at this position. In the course of this investigation, from two strains of Candida krusei we isolated two cytochromes which differ in amino acid composition. One of them seems to correspond to that described in the literature. Two of the differences have been located. [ABSTRACT FROM AUTHOR]

Candida glabrata is an important cause of systemic candidiasis in humans. This paper reports a systematic analysis of the putative glycosylphosphatidylinositol-modified (GPI) proteins of C. glabrata, a large part of which are covalently bound to the cell wall glucan network and the remainder of which are retained in the plasma membrane, and of cell wall proteins (CWPs) which are covalently bound in a mild-alkali-sensitive manner. In silico genomic analysis revealed 106 putative GPI proteins. Fifty-one of these GPI proteins could be categorized as adhesive proteins, potentially implicated in fungus-host interactions or biofilm formation during the development of fungal infections. Eleven proteins belonged to well-known GPI protein families of glycoside hydrolases, probably involved in cell wall expansion and remodelling during growth. Other identified GPI proteins included phospholipases, aspartic proteases, homologues of ScEcm33p and ScKre1p, and structural CWPs. Interestingly, the GPI algorithm predicted three orthologues of an abundant CWP in S. cerevisiae, Cwp1p, which is absent in Candida albicans. To evaluate the in silico predictions, isolated cell walls were extracted using HF-pyridine, which specifically cleaves phosphodiester bonds, to release GPI-CWPs. Immunological analysis of the extract using one-dimensional SDS-PAGE and anti-ScCwp1p antiserum indicated the presence of a Cwp1p homologue in C. glabrata cell walls. Further analysis by two-dimensional gel electrophoresis and electrospray ionization tandem mass spectrometry (ESI-MS/MS) confirmed the presence of two of the predicted Cwp1p proteins, Cwp1.1p and Cwp1.2p. Crh1p, a putative 1,3-β-glucan remodelling enzyme, was also identified. In silico genomic analysis further revealed five putative Pir proteins (Pir1-5p) and five members of the Bgl2 glycoside hydrolase family 17, belonging to a class of putative CWPs that can be extracted with NaOH. Immunological analysis of mild-alkali-extracted CWPs showed the presence of a ScPir2p homologue. Together, these experimental data and in silico predictions represent the first systematic analysis of the C. glabrata cell wall proteome. [ABSTRACT FROM AUTHOR]

First described in 2009 in Japan, the emerging multidrug-resistant fungal pathogen Candida auris is becoming a worldwide public health threat that has been attracting considerable attention due to its rapid and widespread emergence over the past decade. The reasons behind the recent emergence of this fungus remain a mystery to date. Genetic analyses indicate that this fungal pathogen emerged simultaneously in several different continents, where 5 genetically distinct clades of C. auris were isolated from distinct geographical locations. Although C. auris belongs to the CTG clade (its constituent species translate the CTG codon as serine instead of leucine, as in the standard code), C. auris is a haploid fungal species that is more closely related to the haploid and often multidrug-resistant species Candida haemulonii and Candida lusitaniae and is distantly related to the diploid and clinically common fungal pathogens Candida albicans and Candida tropicalis. Infections and outbreaks caused by C. auris in hospitals settings have been rising over the past several years. Difficulty in its identification, multidrug resistance properties, evolution of virulence factors, associated high mortality rates in patients, and long-term survival on surfaces in the environment make C. auris particularly problematic in clinical settings. Here, we review progress made over the past decade on the biological and clinical aspects of C. auris. Future efforts should be directed toward understanding the mechanistic details of its biology, epidemiology, antifungal resistance, and pathogenesis with a goal of developing novel tools and methods for the prevention, diagnosis, and treatment of C. auris infections. [ABSTRACT FROM AUTHOR]

In this study, Candida glabrata, an efficient pyruvate-producing strain, was metabolically engineered for the production of the food ingredient diacetyl. A diacetyl biosynthetic pathway was reconstructed based on genetic modifications and medium optimization. The former included (i) channeling carbon flux into the diacetyl biosynthetic pathway by amplification of acetolactate synthase, (ii) elimination of the branched pathway of α-acetolactate by deleting the ILV5 gene, and (iii) restriction of diacetyl degradation by deleting the BDH gene. The resultant strain showed an almost 1∶1 co-production of α-acetolactate and diacetyl (0.95 g L−1). Furthermore, addition of Fe3+ to the medium enhanced the conversion of α-acetolactate to diacetyl and resulted in a two-fold increase in diacetyl production (2.1 g L−1). In addition, increased carbon flux was further channeled into diacetyl biosynthetic pathway and a titer of 4.7 g L−1 of diacetyl was achieved by altering the vitamin level in the flask culture. Thus, this study illustrates that C. glabrata could be tailored as an attractive platform for enhanced biosynthesis of beneficial products from pyruvate by metabolic engineering strategies. [ABSTRACT FROM AUTHOR]

Candida albicans and Candida dubliniensis are pathogenic fungi that are highly related but differ in virulence and in some phenotypic traits. During in vitro growth on certain nutrient-poor media, C. albicans and C. dubliniensis are the only yeast species which are able to produce chlamydospores, large thick-walled cells of unknown function. Interestingly, only C. dubliniensis forms pseudohyphae with abundant chlamydospores when grown on Staib medium, while C. albicans grows exclusively as a budding yeast. In order to further our understanding of chlamydospore development and assembly, we compared the global transcriptional profile of both species during growth in liquid Staib medium by RNA sequencing. We also included a C. albicans mutant in our study which lacks the morphogenetic transcriptional repressor Nrg1. This strain, which is characterized by its constitutive pseudohyphal growth, specifically produces masses of chlamydospores in Staib medium, similar to C. dubliniensis. This comparative approach identified a set of putatively chlamydospore-related genes. Two of the homologous C. albicans and C. dubliniensis genes (CSP1 and CSP2) which were most strongly upregulated during chlamydospore development were analysed in more detail. By use of the green fluorescent protein as a reporter, the encoded putative cell wall related proteins were found to exclusively localize to C. albicans and C. dubliniensis chlamydospores. Our findings uncover the first chlamydospore specific markers in Candida species and provide novel insights in the complex morphogenetic development of these important fungal pathogens. [ABSTRACT FROM AUTHOR]

The incidence of opportunistic fungal infections has increased in recent decades due to the growing proportion of immunocompromised patients in our society. Candida krusei has been described as a causative agent of disseminated fungal infections in susceptible patients. Although its prevalence remains low among yeast infections (2–5%), its intrinsic resistance to fluconazole makes this yeast important from epidemiologic aspects. Non mammalian organisms are feasible models to study fungal virulence and drug efficacy. In this work we have used the lepidopteran Galleria mellonella and the nematode Caenorhabditis elegans as models to assess antifungal efficacy during infection by C. krusei. This yeast killed G. mellonella at 25, 30 and 37°C and reduced haemocytic density. Infected larvae melanized in a dose-dependent manner. Fluconazole did not protect against C. krusei infection, in contrast to amphotericin B, voriconazole or caspofungin. However, the doses of these antifungals required to obtain larvae protection were always higher during C. krusei infection than during C. albicans infection. Similar results were found in the model host C. elegans. Our work demonstrates that non mammalian models are useful tools to investigate in vivo antifungal efficacy and virulence of C. krusei. [ABSTRACT FROM AUTHOR]

Background: Fungal components have been shown very effective in generating Th17 responses. We investigated whether exposure to a minute amount of C. albicans in the arthritic joint altered the local cytokine environment, leading to enhanced Th17 expansion and resulting in a more destructive arthritis. Methodology: Chronic SCW arthritis was induced by repeated injection with Streptococcus pyogenes (SCW) cell wall fragments into the knee joint of C57Bl/6 mice, alone or in combination with the yeast of C. albicans or Zymosan A. During the chronic phase of the arthritis, the cytokine levels, mRNA expression and histopathological analysis of the joints were performed. To investigate the phenotype of the IL-17 producing T-cells, synovial cells were isolated and analyzed by flowcytometry. Principal Findings: Intra-articular injection of either Zymosan A or C. albicans on top of the SCW injection both resulted in enhanced joint swelling and inflammation compared to the normal SCW group. However, only the addition of C. albicans during SCW arthritis resulted in severe chondrocyte death and enhanced destruction of cartilage and bone. Additionally, exposure to C. albicans led to increased IL-17 in the arthritic joint, which was accompanied by an increased synovial mRNA expression of T-bet and RORγT. Moreover, the C. albicans-injected mice had significantly more Th17 cells in the synovium, of which a large population also produced IFN-γ. Conclusion: This study clearly shows that minute amounts of fungal components, like C. albicans, are very potent in interfering with the local cytokine environment in an arthritic joint, thereby polarizing arthritis towards a more destructive phenotype. [ABSTRACT FROM AUTHOR]