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Oxidative stress responses in the human fungal pathogen, Candida albicans.

Dantas Ada S, Day A, Ikeh M, Kos I, Achan B, Quinn J - Biomolecules (2015)

Bottom Line: Our understanding of how C. albicans senses and responds to ROS has significantly increased in recent years.Furthermore, recent studies have indicated that combinations of the chemical stresses generated by phagocytes can actively prevent C. albicans oxidative stress responses through a mechanism termed the stress pathway interference.In this review, we present an up-date of our current understanding of the role and regulation of oxidative stress responses in this important human fungal pathogen.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Biologia Celular e Genética, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro 20550-013, Brazil. alesdantas@gmail.com.

ABSTRACT
Candida albicans is a major fungal pathogen of humans, causing approximately 400,000 life-threatening systemic infections world-wide each year in severely immunocompromised patients. An important fungicidal mechanism employed by innate immune cells involves the generation of toxic reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. Consequently, there is much interest in the strategies employed by C. albicans to evade the oxidative killing by macrophages and neutrophils. Our understanding of how C. albicans senses and responds to ROS has significantly increased in recent years. Key findings include the observations that hydrogen peroxide triggers the filamentation of this polymorphic fungus and that a superoxide dismutase enzyme with a novel mode of action is expressed at the cell surface of C. albicans. Furthermore, recent studies have indicated that combinations of the chemical stresses generated by phagocytes can actively prevent C. albicans oxidative stress responses through a mechanism termed the stress pathway interference. In this review, we present an up-date of our current understanding of the role and regulation of oxidative stress responses in this important human fungal pathogen.

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H2O2-induced activation of Rad53 triggers filamentation in C. albicans. The redox sensitive oxidoreductase Trx1 inhibits H2O2-induced activation of the DNA damage checkpoint kinase Rad53. This suggests that a regulator of Rad53 is activated by oxidation, and this active oxidised form is reduced by Trx1. Activation of the DNA damage checkpoint triggers the formation of hyperpolarised buds. See text for details.
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biomolecules-05-00142-f003: H2O2-induced activation of Rad53 triggers filamentation in C. albicans. The redox sensitive oxidoreductase Trx1 inhibits H2O2-induced activation of the DNA damage checkpoint kinase Rad53. This suggests that a regulator of Rad53 is activated by oxidation, and this active oxidised form is reduced by Trx1. Activation of the DNA damage checkpoint triggers the formation of hyperpolarised buds. See text for details.

Mentions: Following exposure to H2O2, C. albicans forms hyperpolarised buds, which are morphologically distinct from hyphae and pseudohyphae filamentous forms (Section 3.4). Consistent with this, H2O2-induced hyperpolarized bud formation occurs independently of the key hyphal regulators, Efg1 and Cph1, and, instead, depends on the activation of the Rad53 DNA damage checkpoint pathway [42,61] (Figure 3). A wide range of genotoxic stresses, including UV, methyl methanesulfonate (MMS) and the ribonucleotide reductase inhibitor hydroxyurea have been shown to activate the Rad53 kinase in C. albicans [61], and loss of Rad53 or upstream regulators of Rad53, prevents hyperpolarised bud formation [61,118]. ROS are also genotoxic agents due to the induction of DNA damage [119], which, in turn, triggers the activation of the Rad53 DNA checkpoint pathway [120]. Indeed, treatment of C. albicans cells with H2O2 elicits the phosphorylation of Rad53, and cells lacking RAD53 fail to form hyperpolarised buds in response to H2O2 [42].


Oxidative stress responses in the human fungal pathogen, Candida albicans.

Dantas Ada S, Day A, Ikeh M, Kos I, Achan B, Quinn J - Biomolecules (2015)

H2O2-induced activation of Rad53 triggers filamentation in C. albicans. The redox sensitive oxidoreductase Trx1 inhibits H2O2-induced activation of the DNA damage checkpoint kinase Rad53. This suggests that a regulator of Rad53 is activated by oxidation, and this active oxidised form is reduced by Trx1. Activation of the DNA damage checkpoint triggers the formation of hyperpolarised buds. See text for details.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4384116&req=5

biomolecules-05-00142-f003: H2O2-induced activation of Rad53 triggers filamentation in C. albicans. The redox sensitive oxidoreductase Trx1 inhibits H2O2-induced activation of the DNA damage checkpoint kinase Rad53. This suggests that a regulator of Rad53 is activated by oxidation, and this active oxidised form is reduced by Trx1. Activation of the DNA damage checkpoint triggers the formation of hyperpolarised buds. See text for details.
Mentions: Following exposure to H2O2, C. albicans forms hyperpolarised buds, which are morphologically distinct from hyphae and pseudohyphae filamentous forms (Section 3.4). Consistent with this, H2O2-induced hyperpolarized bud formation occurs independently of the key hyphal regulators, Efg1 and Cph1, and, instead, depends on the activation of the Rad53 DNA damage checkpoint pathway [42,61] (Figure 3). A wide range of genotoxic stresses, including UV, methyl methanesulfonate (MMS) and the ribonucleotide reductase inhibitor hydroxyurea have been shown to activate the Rad53 kinase in C. albicans [61], and loss of Rad53 or upstream regulators of Rad53, prevents hyperpolarised bud formation [61,118]. ROS are also genotoxic agents due to the induction of DNA damage [119], which, in turn, triggers the activation of the Rad53 DNA checkpoint pathway [120]. Indeed, treatment of C. albicans cells with H2O2 elicits the phosphorylation of Rad53, and cells lacking RAD53 fail to form hyperpolarised buds in response to H2O2 [42].

Bottom Line: Our understanding of how C. albicans senses and responds to ROS has significantly increased in recent years.Furthermore, recent studies have indicated that combinations of the chemical stresses generated by phagocytes can actively prevent C. albicans oxidative stress responses through a mechanism termed the stress pathway interference.In this review, we present an up-date of our current understanding of the role and regulation of oxidative stress responses in this important human fungal pathogen.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Biologia Celular e Genética, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro 20550-013, Brazil. alesdantas@gmail.com.

ABSTRACT
Candida albicans is a major fungal pathogen of humans, causing approximately 400,000 life-threatening systemic infections world-wide each year in severely immunocompromised patients. An important fungicidal mechanism employed by innate immune cells involves the generation of toxic reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. Consequently, there is much interest in the strategies employed by C. albicans to evade the oxidative killing by macrophages and neutrophils. Our understanding of how C. albicans senses and responds to ROS has significantly increased in recent years. Key findings include the observations that hydrogen peroxide triggers the filamentation of this polymorphic fungus and that a superoxide dismutase enzyme with a novel mode of action is expressed at the cell surface of C. albicans. Furthermore, recent studies have indicated that combinations of the chemical stresses generated by phagocytes can actively prevent C. albicans oxidative stress responses through a mechanism termed the stress pathway interference. In this review, we present an up-date of our current understanding of the role and regulation of oxidative stress responses in this important human fungal pathogen.

Show MeSH
Related in: MedlinePlus