Programmed Cell Death and Apoptosis in Fungi

Ramsdale, Mark

doi:10.1007/3-540-30809-1_7

Cited by 10 publications

(10 citation statements)

References 244 publications

(254 reference statements)

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Section: Introductionmentioning

confidence: 99%

“…The inactivation of stress signaling pathways or stress genes increases the sensitivity of C. albicans to these environmental stresses and attenuates its virulence (Wysong et al, 1998;Alonso-Monge et al, 1999;Hwang et al, 2002;Martchenko et al, 2004;Fradin et al, 2005). A better understanding of how C. albicans responds to environmental stresses and how these responses are be linked to its cellular fate is important because this may facilitate the design of antifungal therapies that manipulate the endogenous stress and death responses of fungal pathogens (Ramsdale, 2005).The regulation of stress responses in C. albicans appears to have diverged from those in benign model yeasts. Core transcriptional responses to stress differ significantly in C. albicans, S. cerevisiae, and Schizosaccharomyces pombe (Enjalbert et al, 2003(Enjalbert et al, , 2006, as do the roles of the stress activated protein kinases in these yeasts (Hog1/Sty1: Smith et al, 2004;Enjalbert et al, 2006).…”

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confidence: 99%

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MNL1Regulates Weak Acid–induced Stress Responses of the Fungal PathogenCandida albicans

Ramsdale

Selway

Stead

et al. 2008

MBoC

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MNL1, the Candida albicans homologue of an orphan Msn2-like gene (YER130c in Saccharomyces cerevisiae) has no known function. Here we report that MNL1 regulates weak acid stress responses. Deletion of MNL1 prevents the long-term adaptation of C. albicans cells to weak acid stresses and compromises their global transcriptional response under these conditions. The promoters of Mnl1-dependent genes contain a novel STRE-like element (SLE) that imposes Mnl1-dependent, weak acid stress-induced transcription upon a lacZ reporter in C. albicans. The SLE (HHYYCCCCT-TYTY) is related to the Nrg1 response element (NRE) element recognized by the transcriptional repressor Nrg1. Deletion of NRG1 partially restores the ability of C. albicans mnl1 cells to adapt to weak acid stress, indicating that Mnl1 and Nrg1 act antagonistically to regulate this response. Molecular, microarray, and proteomic analyses revealed that Mnl1-dependent adaptation does not occur in cells exposed to proapoptotic or pronecrotic doses of weak acid, suggesting that Ras-pathway activation might suppress the Mnl1-dependent weak acid response in dying cells. Our work defines a role for this YER130c orthologue in stress adaptation and cell death. INTRODUCTIONAll organisms must respond and adapt to environmental stresses if they are to survive adverse conditions. Microbes elicit a combination of specific and general stress responses that repair the damage generated by environmental stresses and restore cellular and metabolic homeostasis under the hostile conditions. These responses are particularly important in pathogenic microbes which have evolved molecular mechanisms to counteract the defenses of their host.In the benign model yeast Saccharomyces cerevisiae, the so-called general stress response or environmental stress response, confers resistance to heat shock, pro-oxidants, osmotic shock, nutrient deprivation, alcohol, and weak acids (Gasch et al., 2000;Causton et al., 2001). This general stress response is largely coordinated by the transcription factors Msn2 and Msn4 (Estruch and Carlson 1993, Marchler et al., 1993). Under stress conditions Msn2 and Msn4 accumulate in the nucleus (Gorner et al., 1998;Jacquet et al., 2003) where they activate the transcription of stress genes containing STRE elements (CCCCT) in their promoters (Martinez-Pastor et al., 1996). This response is down-regulated by the Ras-cAMP-PKA pathway (Garreau et al., 2000). Protein kinase A (PKA)-mediated phosphorylation of Msn2 and Msn4 results in their cytoplasmic accumulation, thereby decreasing the expression of their target stress genes (Gorner et al., 1998(Gorner et al., , 2002.The pathogenic yeast Candida albicans causes frequent infections of the oral and vaginal mucosa and potentially lethal systemic infections in severely immunocompromised individuals, including patients receiving transplants or chemotherapy (Odds, 1988). C. albicans occupies a variety of niches within the human body, encountering a range of stressful conditions as it interacts with its host and counteracts ...

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

MNL1Regulates Weak Acid–induced Stress Responses of the Fungal PathogenCandida albicans

Ramsdale

Selway

Stead

et al. 2008

MBoC

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“…However, single-celled organisms are rarely found as single entities. Instead, they exist alongside their clonal relatives where altruistic cell suicide might have favorable evolutionary repercussions (e.g., by limiting the spread of selfish genetic elements or regulating population density) (11)(12)(13).…”

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confidence: 99%

Ras pathway signaling accelerates programmed cell death in the pathogenic fungus Candida albicans

Phillips

Crowe²,

Ramsdale³

2006

Proc. Natl. Acad. Sci. U.S.A.

137

134

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A better understanding of the molecular basis of programmed cell death (PCD) in fungi could provide information that is useful in the design of antifungal drugs that combat life-threatening fungal infections. Harsh environmental stresses, such as acetic acid or hydrogen peroxide, have been shown to induce PCD in the pathogenic fungus Candida albicans. In this study, we show that dying cells progress from an apoptotic state to a secondary necrotic state and that the rate at which this change occurs is proportional to the intensity of the stimulus. Also, we found that the temporal response is modulated by Ras-cAMP-PKA signals. Mutations that block Ras-cAMP-PKA signaling (ras1⌬, cdc35⌬, tpk1⌬, and tpk2⌬) suppress or delay the apoptotic response, whereas mutations that stimulate signaling (RAS1 val13 and pde2⌬) accelerate the rate of entry of cells into apoptosis. Pharmacological stimulation or inhibition of Ras signaling reinforces these findings. Transient increases in endogenous cAMP occur under conditions that stimulate apoptosis but not growth arrest. Death-specific changes in the abundance of different isoforms of the PKA regulatory subunit, Bcy1p, are also observed. Activation of Ras signals may regulate PCD of C. albicans, either by inhibiting antiapoptotic functions (such as stress responses) or by activating proapoptotic functions.apoptosis ͉ cAMP ͉ necrosis

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“…During the past decade, there has been evidence of programmed cell death (PCD) in fungi (Ramsdale, 2006). PCD involves several different biological processes, among which, externalization of phosphatidylserine and the accumulation of DNA‐strand breaks are characteristic of apoptosis, a specific type of PCD (Hamann et al , 2008).…”

Section: Resultsmentioning

confidence: 99%

Effect of the sesterterpene-type metabolites, ophiobolins A and B, on zygomycetes fungi

Krizsán

Bencsik

Nyilasi

et al. 2010

FEMS Microbiology Letters

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Ophiobolins are sesterterpene-type phytotoxins produced by fungi belonging mainly to the genus Bipolaris. In this study, the antifungal effect of ophiobolins A and B on different zygomycetes has been examined. Depending on the zygomycete tested, MIC values of 3.175-50 μg mL(-1) were found for ophiobolin A and 25-50 μg mL(-1) for ophiobolin B. Ophiobolin A inhibited sporangiospore germination of Mucor circinelloides and caused morphological changes; the fungus formed degenerated, thick or swollen cells with septa. Cytoplasm effusions from the damaged cells were also observed. Fluorescence microscopy after annexin and propidium iodide staining of the treated cells suggested that the drug induced an apoptosis-like cell death process in the fungus.

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Programmed Cell Death and Apoptosis in Fungi

Cited by 10 publications

References 244 publications

MNL1Regulates Weak Acid–induced Stress Responses of the Fungal PathogenCandida albicans

MNL1Regulates Weak Acid–induced Stress Responses of the Fungal PathogenCandida albicans

Ras pathway signaling accelerates programmed cell death in the pathogenic fungus Candida albicans

Effect of the sesterterpene-type metabolites, ophiobolins A and B, on zygomycetes fungi

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