Increased number of glutamine repeats in the C-terminal of Candida albicans Rlm1p enhances the resistance to stress agents

Sampaio, Paula; Nogueira, E.; Loureiro, Ana; Delgado-Silva, Yolanda; Correia, Alexandra; Pais, Célia

doi:10.1007/s10482-009-9352-5

Cited by 26 publications

(28 citation statements)

References 18 publications

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“…The intra-specific TAC variation found here is in agreement with observed variations in the sensitivities of C. albicans isolates to oxidants 47 . However, the TAC results did not correlate (rho = 0.051) with the previously reported sensitivity of Candida sp.…”

supporting

confidence: 91%

Glutathione levels in and total antioxidant capacity of Candida sp. cells exposed to oxidative stress caused by hydrogen peroxide

Abegg

Alabarse

Schüller

et al. 2012

Rev. Soc. Bras. Med. Trop.

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Candida albicans, C. glabrata, C. tropicalis, and C. parapsilosis account for approximately 95% of identifiable Candida infections. Other species, including C. krusei, C. lusitaniae, and C. guilliermondii, account for less than 5% of cases of invasive candidiasis. The most common causative agent is still C. albicans, but its incidence is declining and the frequencies of other species are increasing. Recently, Furlaneto et al. 1 noted that non-albicans Candida was the predominant species in different clinical specimens, with the exception of urine samples, in a Brazilian tertiary-care hospital. Invasive candidiasis has a mortality rate that approaches 40% 2,3 . Although most people are colonized by Candida sp., the majority never develop invasive candidiasis. Alterations in host immunity, physiological features, or normal microflora, rather than the acquisition of novel or hypervirulent factors by Candida, are suggested to degenerate the commensal-host interaction and lead to an opportunistic infection 4 .During the course of a systemic infection, Candida cells are engulfed by host phagocytes, where they are exposed to reactive oxygen species (ROS) 5 . ROS contribute to the killing of C. albicans in both cultured cells and entire organisms [6][7][8][9] . Upon incubation with macrophages, C. albicans deoxyribonucleic acid (DNA) repair genes are transcriptionally induced, suggesting that DNA damage indeed occurs in the phagosome and that genotoxic hypersensitivity stress would be disadvantageous to the pathogen 10 . Recently, it was demonstrated that a large proportion of C. albicans cell surface antigens related to acute candidemia are involved in oxidative stress 4 . In C. albicans, hyphal cells ABSTRACT Introduction: The capacity to overcome the oxidative stress imposed by phagocytes seems to be critical for Candida species to cause invasive candidiasis. Methods: To better characterize the oxidative stress response (OSR) of 8 clinically relevant Candida sp., glutathione, a vital component of the intracellular redox balance, was measured using the 5,5'-dithiobis-(2-nitrobenzoic acid (DTNB)-glutathione disulfide (GSSG) reductase reconversion method; the total antioxidant capacity (TAC) was measured using a modified method based on the decolorization of the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic) acid radical cation (ABTS* + ). Both methods were used with cellular Candida sp. extracts treated or not with hydrogen peroxide (0.5 mM). Results: Oxidative stress induced by hydrogen peroxide clearly reduced intracellular glutathione levels. This depletion was stronger in Candida albicans and the levels of glutathione in untreated cells were also higher in this species. The TAC demonstrated intra-specific variation. Conclusions: Glutathione levels did not correlate with the measured TAC values, despite this being the most important non-enzymatic intracellular antioxidant molecule. The results indicate that the isolated measurement of TAC does not give a clear picture of the ability of a given Candida sp. to resp...

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supporting

confidence: 91%

Glutathione levels in and total antioxidant capacity of Candida sp. cells exposed to oxidative stress caused by hydrogen peroxide

Abegg

Alabarse

Schüller

et al. 2012

Rev. Soc. Bras. Med. Trop.

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“…The CLSI M27 A3 broth microdilution susceptibility method was used to examine the activities of agents associated with cell wall stress against planktonic C. albicans (29,33). Agents with various mechanisms of action known to impact cell integrity were included (48). MICs were recorded visually and by absorbance reading at 550 nm.…”

Section: Methodsmentioning

confidence: 99%

Interface of Candida albicans Biofilm Matrix-Associated Drug Resistance and Cell Wall Integrity Regulation

et al. 2011

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Candida albicans frequently infects medical devices by growing as a biofilm, i.e., a community of adherent organisms entrenched in an extracellular matrix. During biofilm growth, Candida spp. acquire the ability to resist high concentrations of antifungal drugs. One recently recognized biofilm resistance mechanism involves drug sequestration by matrix ␤-1,3 glucan. Using a candidate gene approach, we investigated potential C. albicans ␤-1,3-glucan regulators, based on their homology to Saccharomyces cerevisiae, including SMI1 and protein kinase C (PKC) pathway components. We identified a role for the SMI1 in biofilm matrix glucan production and development of the associated drug resistance phenotype. This pathway appears to act through transcription factor Rlmp and glucan synthase Fks1p. The phenotypes of these mutant biofilms mimicked those of the smi1⌬/smi1⌬ biofilm, and overexpression of FKS1 in the smi1⌬/smi1⌬ mutant restored the biofilm resistant phenotype. However, control of this pathway is distinct from that of the upstream PKC pathway because the pkc1⌬/pkc1⌬, bck1⌬/bck1⌬, mkk2⌬/mkk2⌬, and mkc1⌬/mkc1⌬ biofilms retained the resistant phenotype of the parent strain. In addition, resistance to cell-perturbing agents and gene expression data do not support a significant role for the cell wall integrity pathway during the biofilm formation. Here we show that Smi1p functions in conjunction with Rlm1p and Fks1p to produce drug-sequestering biofilm ␤-glucan. Our work provides new insight into how the C. albicans biofilm matrix production and drug resistance pathways intersect with the planktonic cell wall integrity pathway. This novel connection helps explain how pathogens in a multicellular biofilm community are protected from anti-infective therapy.

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“…Many techniques are used for molecular characterization of Candida species, such as Restriction Fragment Length Polymorphism (RFLP) [41], DNA fingerprinting [42], electrophoretic karyotyping [43], Random Amplified Polymorphic DNA (RAPD) [44], Multilocus Enzyme Electrophoresis (MLEE) [45], and sequencing of microsatellites [46]. However, in order to estimate genetic distances and infer phylogenetic relationships between species that can be easily evaluated in terms of probability models, the most suitable techniques involve gene sequencing and produce topologies built from nucleotide or amino acid sequences.…”

Section: Molecular Methods Developed For the Identification And Charamentioning

confidence: 99%

Molecular Methods Developed for the Identification and Characterization of Candida Species

Grisolia¹

2017

IJGS

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Candida species are commensally microorganisms in healthy individuals, but is also the most opportunistic fungal pathogen of human. From benign skin-mucosal forms to invasive ones, Candida infection, can compromise various organs systematic and cause diseases in immunocompromised or critically ill patients. Hence the accurate identification and characterization of the disease-causing strains is crucial for diagnosis, clinical treatment and epidemiological studies of candidacies. Molecular methods the identification and characterization support gives in epidemiological research and in development of novel antifungal with specific molecular targets, especially in the case of resistant Candida species. This review aims to describe the main methods used in the identification and characterization the Candida species and discusses future perspectives.

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Increased number of glutamine repeats in the C-terminal of Candida albicans Rlm1p enhances the resistance to stress agents

Cited by 26 publications

References 18 publications

Glutathione levels in and total antioxidant capacity of Candida sp. cells exposed to oxidative stress caused by hydrogen peroxide

Glutathione levels in and total antioxidant capacity of Candida sp. cells exposed to oxidative stress caused by hydrogen peroxide

Interface of Candida albicans Biofilm Matrix-Associated Drug Resistance and Cell Wall Integrity Regulation

Molecular Methods Developed for the Identification and Characterization of Candida Species

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