Candida and candidiasis in HIV-infected patients: where commensalism, opportunistic behavior and frank pathogenicity lose their borders
ABSTRACT In this era of efficacious antiretroviral therapy and consequent immune reconstitution, oropharyngeal and esophageal candidiasis (OPC and OEC) still remain two clinically relevant presentations in the global HIV setting. Both diseases are predominantly caused by Candida albicans, a polymorphic fungus which is a commensal microbe in the healthy individual but can become an aggressive pathogen in a debilitated host. Actually, C. albicans commensalism is not the result of a benign behavior of one of the many components of human microbiota, but rather the result of host's potent innate and adaptive immune responses that restrict the growth of a potentially dangerous microrganism on the epithelia. An important asset guarding against the fungus is the Th17 functional subset of T helper cells. The selective loss of these cells with the progression of HIV infection causes the decay of fungal containment on the oral epithelium and allows C. albicans to express its pathogenic potential. An important part of this potential is represented by mechanisms to evade host immunity and enhance inflammation and immunoactivation. In C. albicans, these mechanisms are mostly incorporated into and expressed by characteristic morphogenic transitions such as the yeast-to-hyphal growth and the white-to-opaque switch. In addition, HIV infection generates an 'environment' selecting for overexpression of the virulence potential by the fungus, particularly concerning the secreted aspartyl proteinases (Saps). These enzymes can degrade critical host defense components such as complement and epithelial defensive proteins such as histatin-5 and E-cadherin. It appears that part of this enhanced Candida virulence could be induced by the binding of the fungus to HIV and/or induced by HIV proteins such as GP160 and tat. Both OPC and OEC can be controlled by old and new antimycotics, but in the absence of host collaboration, anticandidal therapy may become ineffective in the long run. For these reasons, new therapeutics targeting virulence factors and specific immune interventions are being addressed. Among these new approaches, vaccination is a promising one. Two subunit vaccines based on antigens dominantly expressed by C. albicans in vivo, that is the Als3 adhesin and Sap2, have recently undergone phase 1 clinical trials. Overall, studies of Candida and candidiasis in the HIV-positive patient while certainly contributing to a more effective control of the microorganism may also provide useful information on HIV-host relationship itself that can assist the fight against the virus.
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ABSTRACT: To analyze the essentiality of the ROM2 genes originating from the pathogenic yeast Candida glabrata and C. albicans by using temperature-sensitive (ts) mutants. Based on the general concepts that ts mutations are generated by virtue of point mutation within essential genes, we have previously established a novel method (termed 'ETS system' for screening and identification of essential genes using ts mutants of C. glabrata). According to this ETS system, the present study successfully identified a putative C. glabrata ROM2 homologue as an essential gene that complements its point mutation (Cys-1275/Tyr substitution). The C. albicans ROM2 mutant (Cys-1281/Tyr), constructed patterned after this point mutation, also displayed ts phenotype. Both ts mutants recovered colony-forming ability, with concomitant suppression of lysis phenotype, at the elevated temperature in the presence of 1 mol l(-1) sorbitol as an osmotic stabilizer. Sequence alignment revealed that human genome possesses relatively low homology against Rom2 homologues, which are highly conserved among yeast species. ROM2 genes of C. glabrata and C. albicans are essential for viability, probably involved in cell wall integrity. ROM2 genes essential for both Candida species may be potentially useful antifungal targets from chemotherapeutic viewpoint. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Journal of Applied Microbiology 01/2015; 118(4). DOI:10.1111/jam.12745 · 2.39 Impact Factor
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ABSTRACT: The aim of this study was to assess the prevalence of oral lesions in infectious-contagious diseases patients being treated in the University Hospital of the Federal University of Pará, northern Brazil. One hundred seven patients with infectious diseases were clinically investigated for oral lesions at the University Hospital of Pará, northern Brazil. From total sample, most patients were men (65.7%) with a mean age of 45.4 years. About prevalence of systemic diseases, tuberculosis was the most frequent illness, followed by AIDS, hepatitis types B and C, leishmaniasis, and meningitis. Analyzing oral manifestations, periodontal diseases and candidiasis were the most prevalent diseases in both genders, followed by recurrent aphthous ulcers, saburral tongue, simplex herpes, and squamous cell carcinoma. Of all 107 patients, only 10 males and 6 females did not present any oral manifestation. There was no statistical difference between genders with any systemic condition (P > 0.05). The great prevalence of oral manifestations in hospitalized patients with systemic disorder emphasizes the need of integral dental care in this context, aiming at a multidisciplinary approach of patients. Therefore, presence of some oral conditions, such as candidiasis, should be an alert to different systemic conditions, once in assistance with physicians; dentists can influence the early diagnosis and treatment.The Scientific World Journal 01/2014; 2014:586075. DOI:10.1155/2014/586075 · 1.73 Impact Factor
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ABSTRACT: Candida albicans is a fungal pathogen that causes potentially fatal infections among immune-compromised individuals. The emergence of drug resistant C. albicans strains makes it important to identify new antifungal drug targets. Among potential targets are enzymes known as peptidyl-prolyl cis/trans isomerases (PPIases) that catalyze isomerization of peptide bonds preceding proline. We are investigating a PPIase called Ess1, which is conserved in all major human pathogenic fungi. Previously, we reported that C. albicans Ess1 is essential for growth and morphogenetic switching. In the present study, we re-evaluated these findings using more rigorous genetic analyses, including the use of additional CaESS1 mutant alleles, distinct marker genes, and the engineering of suitably-matched isogenic control strains. The results confirm that CaEss1 is essential for growth in C. albicans, but show that reduction of CaESS1 gene dosage by half (δ/+) does not interfere with morphogenetic switching. However, further reduction of CaEss1 levels using a conditional allele does reduce morphogenetic switching. We also examine the role of the linker α-helix that distinguishes C. albicans Ess1 from the human Pin1 enzyme, and present results of a genome-wide transcriptome analysis. The latter analysis indicates that CaEss1 has a conserved role in regulation of RNA polymerase II function, and is required for efficient termination of small nucleolar RNAs and repression of cryptic transcription in C. albicans.PLoS ONE 03/2013; 8(3):e59094. DOI:10.1371/journal.pone.0059094 · 3.53 Impact Factor