Mechanisms of Resistance to Oxidative and Nitrosative Stress: Implications for Fungal Survival in Mammalian Hosts

Missall, Tricia A.; Lodge, Jennifer K.; McEwen, Joan E.

doi:10.1128/ec.3.4.835-846.2004

Cited by 193 publications

(155 citation statements)

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“…C. albicans shows great natural resistance to oxidative stress resulting mainly from the activity of numerous anti-oxidative enzymes (e.g. catalase, superoxide dismutases, glutathione oxidase) (Missall et al, 2004). Based on our results, it can be suggested that the SFs had a direct effect on Candida cell wall stability rather than on the activity of the enzymes mentioned above.…”

mentioning

confidence: 52%

New pharmacological properties of Medicago sativa and Saponaria officinalis saponin-rich fractions addressed to Candida albicans

Sadowska

Budzyńska

Więckowska-Szakiel

et al. 2014

Journal of Medical Microbiology

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The antifungal activity of the saponin-rich fractions (SFs) from Medicago sativa (aerial parts and roots) and Saponaria officinalis (used as a well-known source of plant saponins) against Candida albicans reference and clinical strains, their yeast-to-hyphal conversion, adhesion, and biofilm formation was investigated. Direct fungicidal/fungistatic properties of the tested phytochemicals used alone, as well as their synergy with azoles (probably resulting from yeast cell wall instability) were demonstrated. Here, to the best of our knowledge, we report for the first time the ability of saponin-rich extracts of M. sativa and S. officinalis to inhibit C. albicans germ tube formation, limit hyphal growth, reduce yeast adherence and biofilm formation, and eradicate mature (24 h) Candida biofilm. Moreover, M. sativa SFs (mainly obtained from aerial parts), in the range of concentrations which were active modulators of Candida virulence factors, exhibited low cytotoxicity against the mouse fibroblast line L929. These properties seem to be very promising in the context of using plant-derived SFs as potential novel antifungal therapeutics supporting classic drugs or as ingredients of disinfectants. INTRODUCTIONCandida albicans is probably the best known and at the same time the most effective opportunistic fungal pathogen of humans and animals. It constitutes a commensal microflora in the gastrointestinal and genitourinary tracts of .70 % of humans. However, in certain circumstances C. albicans could be pathogenic to critically ill, immunocompromised patients or even to healthy persons. It causes a diverse range of pathologies -from local cutaneous and mucosal infections (e.g. candidiasis of nail shafts and nails, oropharyngeal candidiasis, intestinal candidiasis) to lifethreatening systemic infections, such as candidaemia, fungal pneumonia, meningitidis or endocarditis (Cannon et al., 2009;Kabir et al., 2012;Kabir & Ahmad, 2013;Sardi et al., 2013; Tlamçani & Er-rami, 2013). Endogenous candidaemia and the carrier state are the main mechanisms of Candida spp. spread and transmission, although exogenous infections are also possible (Mathé & van Dijck, 2013;Sardi et al., 2013). The pathogenicity and high invasiveness of C. albicans arise from the broad range of its virulence factors. These include tissue-damaging hydrolytic enzymes: proteases (mainly secreted aspartic proteinases), phospholipases and haemolysins, but first of all the agents/abilities contributing to its strong adherence (e.g. two main C. albicans adhesions: agglutinin-like sequence and hyphal wall protein-1), biofilm formation and the transformation of morphological forms (yeast-to-hyphal). Also, the ability of C. albicans to survive in various anatomical body sites and to evade host defences seems to be essential (Chai et al., 2009;Chandra et al., 2001;Gropp et al., 2009;Sardi et al., 2013).Invasive candidiasis usually results from tissue colonization by yeast and formation of biofilm -the structured multicellular microbial communities embedded in a self-...

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mentioning

confidence: 52%

New pharmacological properties of Medicago sativa and Saponaria officinalis saponin-rich fractions addressed to Candida albicans

Sadowska

Budzyńska

Więckowska-Szakiel

et al. 2014

Journal of Medical Microbiology

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“…Macrophages and neutrophils use ROS, reactive nitrogen species (RNS), and chlorine species for host protection [6][7][8][9]63 , but the idea that ROS exert direct in vivo effects in the fungal killing of Candida and other species is still controversial. Balish et al 64 studied the deficient production of ROS and RNS in mice using gastrointestinal Candida inoculation.…”

Section: Acknowledgmentsmentioning

confidence: 99%

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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“…Glutathione peroxidases have not been studied in any fungal pathogen (Missall et al, 2004a), though a glutathione peroxidase homologue has been shown to be transcriptionally abundant during experimental cryptococcosis (Steen et al, 2003). Here, we determine the expression patterns and localization of the two glutathione peroxidases and test their importance to stress resistance, macrophage survival and mammalian virulence of the fungal pathogen C. neoformans.…”

Section: Introductionmentioning

confidence: 99%

Two glutathione peroxidases in the fungal pathogen Cryptococcus neoformans are expressed in the presence of specific substrates

2005

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Glutathione peroxidases catalyse the reduction of peroxides by reduced glutathione. To determine if these enzymes are important for resistance to oxidative stress and evasion of the innate immune system by the fungal pathogen Cryptococcus neoformans, two glutathione peroxidase homologues, which share 38 % identity, were identified and investigated. In this study, these peroxidases, Gpx1 and Gpx2, their localization, their contribution to total glutathione peroxidase activity, and their importance to the oxidative and nitrosative stress resistance of C. neoformans are described. It is shown that the two glutathione peroxidase genes are differentially expressed in response to stress. While both GPX1 and GPX2 are induced during t-butylhydroperoxide or cumene hydroperoxide stress and repressed during nitric oxide stress, only GPX2 is induced in response to hydrogen peroxide stress. Deletion mutants of each and both of the glutathione peroxidases were generated, and it was found that they are sensitive to various peroxide stresses while showing wild-type resistance to other oxidant stresses, such as superoxide and nitric oxide. While the glutathione peroxidase mutants are slightly sensitive to oxidant killing by macrophages, they exhibit wild-type virulence in a mouse model of cryptococcosis.

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Mechanisms of Resistance to Oxidative and Nitrosative Stress: Implications for Fungal Survival in Mammalian Hosts

Cited by 193 publications

References 195 publications

New pharmacological properties of Medicago sativa and Saponaria officinalis saponin-rich fractions addressed to Candida albicans

New pharmacological properties of Medicago sativa and Saponaria officinalis saponin-rich fractions addressed to Candida albicans

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

Two glutathione peroxidases in the fungal pathogen Cryptococcus neoformans are expressed in the presence of specific substrates

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