Alteration in Membrane Fluidity and Lipid Composition, and Modulation of H+-ATPase Activity in Saccharomyces Cerevisiae caused by Decanoic Acid

Alexandre, Hervé; Mathieu, Bruno; Charpentier, Claudine

doi:10.1099/13500872-142-3-469

Cited by 97 publications

(72 citation statements)

References 32 publications

(46 reference statements)

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“…However, no clear ortholog of PDR12 exists in the C. albicans genome. Other possible resistance mechanisms include alteration of the plasma membrane lipid composition (47) or other as-yet-undocumented mechanisms.…”

Section: Discussionmentioning

confidence: 99%

MIG1Regulates Resistance of Candida albicans against the Fungistatic Effect of Weak Organic Acids

Cottier

Tan

et al. 2015

Eukaryot Cell

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bCandida albicans is the leading cause of fungal infections; but it is also a member of the human microbiome, an ecosystem of thousands of microbial species potentially influencing the outcome of host-fungal interactions. Accordingly, antibacterial therapy raises the risk of candidiasis, yet the underlying mechanism is currently not fully understood. We hypothesize the existence of bacterial metabolites that normally control C. albicans growth and of fungal resistance mechanisms against these metabolites. Among the most abundant microbiota-derived metabolites found on human mucosal surfaces are weak organic acids (WOAs), such as acetic, propionic, butyric, and lactic acid. Here, we used quantitative growth assays to investigate the dose-dependent fungistatic properties of WOAs on C. albicans growth and found inhibition of growth to occur at physiologically relevant concentrations and pH values. This effect was conserved across distantly related fungal species both inside and outside the CTG clade. We next screened a library of transcription factor mutants and identified several genes required for the resistance of C. albicans to one or more WOAs. A single gene, MIG1, previously known for its role in glucose repression, conferred resistance against all four acids tested. Consistent with glucose being an upstream activator of Mig1p, the presence of this carbon source was required for WOA resistance in wild-type C. albicans. Conversely, a MIG1-complemented strain completely restored the glucose-dependent resistance against WOAs. We conclude that Mig1p plays a central role in orchestrating a transcriptional program to fight against the fungistatic effect of this class of highly abundant metabolites produced by the gastrointestinal tract microbiota.O ver 60% of fungal infections are caused by Candida albicans, and these infections range from debilitating skin or mucosal infections to potentially lethal disseminated disease, most especially in immunocompromised individuals and in nosocomial settings (1, 2). At the same time, this species is also the fungus most frequently isolated from the oral cavity, the vaginal mucosa, and the gastrointestinal (GI) tract of most healthy individuals (2), indicating a commensal nature of the host-microbe interaction in unperturbed conditions. A switch from asymptomatic colonization to opportunistic infection is supported by evidence of strain relatedness between C. albicans isolates from blood cultures and from the GI tract of the same patients (3). Hence, controlling C. albicans growth in the GI tract might limit one of the primary sources of systemic candidiasis.Antibiotic treatment, which is well known to profoundly modify the GI microbiome (4, 5), is a strong risk factor for both vulvovaginal and systemic candidiasis in humans (6, 7). Moreover, most mouse models of C. albicans GI colonization rely on oral antibiotic treatment (8-10). Other models rely on the use of germfree mice (11), infant mice (12, 13), which harbor a significantly different GI microbiome than adults (14), or ...

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Section: Discussionmentioning

confidence: 99%

MIG1Regulates Resistance of Candida albicans against the Fungistatic Effect of Weak Organic Acids

Cottier

Tan

et al. 2015

Eukaryot Cell

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“…Similar changes in the abundance ratio of unsaturated fatty acids have been found as part of the adaptation processes of yeasts to stress conditions. For example, S. cereuisiae increases the amount of oleic acid at the expense of palmitoleic acid as a response to the presence of decanoic acid (a toxin produced during fermentation) in the growth medium (Alexandre et al, 1996) and a similar response is observed in the presence of ethanol (Sajbidor & Grego, 1992). Also, work on 7'.…”

Section: Fatty Acidsmentioning

confidence: 99%

Fungicides and sterol-deficient mutants of Ustilago maydis: plasma membrane physico-chemical characteristics do not explain growth inhibition

et al. 1997

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Plasma membrane vesicles from erg1 I and erg2 sterol-deficient mutants and from wild-type Ustilago maydis sporidia treated with and without inhibitors of sterol 14a-demethylase or sterol A8-A7 isomerase (triadimenol and fenpropimorph fungicides, respectively) were purified by aqueous two-phase partitioning. Changes in plasma membrane lipid composition were mostly restricted to sterols and complex lipid-bound fatty acids (CLB fatty acids). There was a greater accumulation of abnormal sterols (14a-methyl-or A8-unsaturated sterols) in plasma membranes from sterol-def icient mutants than from those treated with their fungicide counterparts. However, greater growth inhibition was observed on fungicide-treated wild-type than on mutants. Changes in CLB fatty acids were restricted to alterations in the relative proportion of linoleic acid (18:2) with respect to oleic acid (18: 1). The 18:2 to 18:l ratio found in CLB fatty acids in plasma membranes could be correlated to rates of sporidial growth but not to accumulation of a particular abnormal sterol or to the extent of sterol replacement. Plasma membrane permeability to protons was increased moderately in the mutants only. No changes were observed in plasma membrane fluidity. Plasma membrane H+-ATPase activity was increased up to twofold in those cases with lower growth rate. It was concluded that fungiciddnduced growth inhibition in U. maydis was not due to accumulation of abnormal sterols in plasma membranes but probably due to intracellular ATP depletion by the H+-ATPase and that changes in 18:2 to 18: 1 ratio in CLB fatty acids were not directly dependent on the plasma membrane physical state or lipid composition but were possibly part of a stress adaptation mechanism.

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“…Several factors can lead to stuck fermentation, such as insufficient nitrogen, the low lipidic content of the grape must, and high concentrations of mediumchain fatty acids (MCFA) in the fermenting must (3). The main MCFA, octanoic and decanoic acids, are produced by yeasts during alcoholic fermentation as by-products of lipid synthesis (40).…”

mentioning

confidence: 99%

“…The toxicity of short-to mediumchain fatty acids also is correlated with their lipophilic properties, indicating a probable effect on the cell membrane (45). Indeed, decanoic acid, the more toxic of the two compounds (49), has been shown to increase membrane permeability (3). However, the rapid exposure of yeast cells to sublethal concentrations of octanoic acid provokes an adaptive response, allowing the cells to resist larger amounts of inhibitor (7).…”

mentioning

confidence: 99%

Activation of Two Different Resistance Mechanisms in Saccharomyces cerevisiae upon Exposure to Octanoic and Decanoic Acids

Legras

Erny

Jeune

et al. 2010

Appl Environ Microbiol

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Medium-chain fatty acids (octanoic and decanoic acids) are well known as fermentation inhibitors. During must fermentation, the toxicity of these fatty acids is enhanced by ethanol and low pH, which favors their entrance in the cell, resulting in a decrease of internal pH. We present here the characterization of the mechanisms involved in the establishment of the resistance to these fatty acids. The analysis of the transcriptome response to the exposure to octanoic and decanoic acids revealed that two partially overlapping mechanisms are activated; both responses share many genes with an oxidative stress response, but some key genes were activated differentially. The transcriptome response to octanoic acid stress can be described mainly as a weak acid response, and it involves Pdr12p as the main transporter. The phenotypic analysis of knocked-out strains confirmed the role of the Pdr12p transporter under the control of WAR1 but also revealed the involvement of the Tpo1p major facilitator superfamily proteins (MFS) transporter in octanoic acid expulsion. In contrast, the resistance to decanoic acid is composite. It also involves the transporter Tpo1p and includes the activation of several genes of the beta-oxidation pathway and ethyl ester synthesis. Indeed, the induction of FAA1 and EEB1, coding for a long-chain fatty acyl coenzyme A synthetase and an alcohol acyltransferase, respectively, suggests a detoxification pathway through the production of decanoate ethyl ester. These results are confirmed by the sensitivity of strains bearing deletions for the transcription factors encoded by PDR1, STB5, OAF1, and PIP2 genes.

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Alteration in Membrane Fluidity and Lipid Composition, and Modulation of H+-ATPase Activity in Saccharomyces Cerevisiae caused by Decanoic Acid

Cited by 97 publications

References 32 publications

MIG1Regulates Resistance of Candida albicans against the Fungistatic Effect of Weak Organic Acids

MIG1Regulates Resistance of Candida albicans against the Fungistatic Effect of Weak Organic Acids

Fungicides and sterol-deficient mutants of Ustilago maydis: plasma membrane physico-chemical characteristics do not explain growth inhibition

Activation of Two Different Resistance Mechanisms in Saccharomyces cerevisiae upon Exposure to Octanoic and Decanoic Acids

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