An alternate respiratory pathway in Candida albicans

Kot, E. J.; Olson, V. L.; Rolewic, L. J.; McClary, Dan O.

doi:10.1007/bf00399447

Cited by 28 publications

(15 citation statements)

References 24 publications

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“…Growth in a medium amended with a Cyt inhibitor leads to 02 consumption which is fully resistant to cyanide and sensitive to SHAM. These results indicate a high level of activity of the alternate system and are similar to reports of CNinsensitive respiration in Neurospora crassa (12,15) and in Candida albicans (11) for which antimycin and SHAM have been used similarly to illustrate that the CN insensitivity is associated with an alternate respiratory system.…”

supporting

confidence: 87%

Contribution of a Cyanide-insensitive Alternate Respiratory System to Increases in Formamide Hydro-lyase Activity and to Growth in Stemphylium loti in Vitro

Rissler¹,

Millar²

1977

Plant Physiol.

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Stemphylium lotn, a pathogen of a cyanogenc plant, possesses a cyanide-isensitive alternate respiratory pathway. In the absence of cytochrome inhibitors, the alternate system had only a minor role in resption. When S. loi was grown in medium amended with antimycin to block the cytochrome chain, the alternate system accounted for the total oxygen consumption ocited with respiration. Hydrogen cyanide is released from cyanogenic glucosides in birdsfoot trefoil (Lotus corniculatus L.) upon infection by Stemphylium loti (16). This fungus grows in the presence of relatively high concentrations of cyanide in vitro (3) and is more tolerant of cyanide than are other fungi (16). reported that cyanide tolerance in S. loti is induced upon exposure to cyanide and is due to the production of the enzyme formamide hydro-lyase which converts cyanide to nontoxic formamide.We Cyanide-insensitive respiration is generally associated with an unidentified alternate terminal oxidase (ATO) (8) which reportedly connects with the normal electron transport chain at ubiquinone (24). This alternate respiratory pathway coexists with the normal respiratory chain in mitochondria (8). Studies of the normal and alternate respiratory systems have shown the following: (a) antimycin, cyanide, azide, and carbon monoxide, through inhibition of certain Cyt in the normal electron transport chain, inhibit the normal respiratory system but not the alternate pathway (9, 14, 25); (b) salicylhydroxamic acid specifically inhibits the alternate pathway but not the normal pathway (20); and (c) the addition of Cyt inhibitors to a growth medium promotes the appearance of the alternate respiratory pathway in microorganisms such that 100% of the respiration is insensitive to cyanide but is sensitive to SHAM (6,10,12).Our objectives were to determine if S. loti possesses a cyanideinsensitive alternate respiratory pathway and to assess the contribution of such an alternate pathway to growth and to increases in FHL activity. A preliminary report of this work has been published (17). MATERIALS AND METHODS

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supporting

confidence: 87%

Contribution of a Cyanide-insensitive Alternate Respiratory System to Increases in Formamide Hydro-lyase Activity and to Growth in Stemphylium loti in Vitro

Rissler¹,

Millar²

1977

Plant Physiol.

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“…We first measured the respiration rate by detecting O 2 consumption. In addition to the classical respiratory chain, Candida species possess an alternative route of electron transfer and oxygen reduction, mainly based on alternative oxidases (62,63), which are sensitive to the inhibitor SHAM. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

The Production of Reactive Oxygen Species Is a Universal Action Mechanism of Amphotericin B against Pathogenic Yeasts and Contributes to the Fungicidal Effect of This Drug

Mesa-Arango

Trevijano-Contador

Román

et al. 2014

Antimicrob Agents Chemother

189

151

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e Amphotericin B (AMB) is an antifungal drug that binds to ergosterol and forms pores at the cell membrane, causing the loss of ions. In addition, AMB induces the accumulation of reactive oxygen species (ROS), and although these molecules have multiple deleterious effects on fungal cells, their specific role in the action mechanism of AMB remains unknown. In this work, we studied the role of ROS in the action mechanism of AMB. We determined the intracellular induction of ROS in 44 isolates of different pathogenic yeast species (Candida albicans, Candida parapsilosis, Candida glabrata, Candida tropicalis, Candida krusei, Cryptococcus neoformans, and Cryptococcus gattii). We also characterized the production of ROS in AMB-resistant isolates. We found that AMB induces the formation of ROS in all the species tested. The inhibition of the mitochondrial respiratory chain by rotenone blocked the induction of ROS by AMB and provided protection from the killing action of the antifungal. Moreover, this phenomenon was absent in strains that displayed resistance to AMB. These strains showed an alteration in the respiration rate and mitochondrial membrane potential and also had higher catalase activity than that of the AMB-susceptible strains. Consistently, AMB failed to induce protein carbonylation in the resistant strains. Our data demonstrate that the production of ROS by AMB is a universal and important action mechanism that is correlated with the fungicidal effect and might explain the low rate of resistance to the molecule. Finally, these data provide an opportunity to design new strategies to improve the efficacy of this antifungal.

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“…HGT4 appears to be important for fermentation because it is required for growth in the presence of antimycin A, which substantially inhibits respiration by blocking electron transfer between cytochromes b and c (14). Wild-type C. albicans is able to carry out some respiration in the presence of antimycin A because it has the alternative oxidases Aox1 (encoded by orf19.4774) and Aox2 (encoded by orf19.4773) that function when cytochromes b and c are inhibited (24) and AOX2 expression is induced by antimycin A (16). AOX2 expression is also induced by the glucose signal generated by Hgt4 (Table 2), and this may account for the severe growth defect of the hgt4⌬ mutant on glucose plus antimycin A.…”

Section: Discussionmentioning

confidence: 99%

“…Hgt4 is also required for growth on glucose in the presence of antimycin A, which substantially inhibits respiration (Fig. 3) (14,24). Mutants defective in another glucose sensing pathway triggered by the Gpr1 G-protein coupled receptor and its G protein alpha Gpa2 appear to ferment glucose normally (Fig.…”

Section: Fig 4 (A)mentioning

confidence: 99%

A Glucose Sensor in Candida albicans

2006

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The Hgt4 protein of Candida albicans (orf19.5962) is orthologous to the Snf3 and Rgt2 glucose sensors of Saccharomyces cerevisiae that govern sugar acquisition by regulating the expression of genes encoding hexose transporters. We found that HGT4 is required for glucose induction of the expression of HGT12, HXT10, and HGT7, which encode apparent hexose transporters in C. albicans. An hgt4⌬ mutant is defective for growth on fermentable sugars, which is consistent with the idea that Hgt4 is a sensor of glucose and similar sugars. Hgt4 appears to be sensitive to glucose levels similar to those in human serum (ϳ5 mM). HGT4 expression is repressed by high levels of glucose, which is consistent with the idea that it encodes a high-affinity sugar sensor. Glucose sensing through Hgt4 affects the yeast-to-hyphal morphological switch of C. albicans cells: hgt4⌬ mutants are hypofilamented, and a constitutively signaling form of Hgt4 confers hyperfilamentation of cells. The hgt4⌬ mutant is less virulent than wild-type cells in a mouse model of disseminated candidiasis. These results suggest that Hgt4 is a high-affinity glucose sensor that contributes to the virulence of C. albicans.Candida albicans is responsible for most yeast infections in humans. In addition to causing ordinary vaginal and oral (thrush) infections, this fungus is a serious threat to immunocompromised patients, for whom disseminated, invasive candidiasis is common and often fatal (31, 56). The fungus is normally maintained as a harmless commensal on skin, on mucosa, and in the gut (23) but becomes an opportunistic pathogen upon entry into the bloodstream of immunocompromised (particularly neutropenic) individuals (25,45).

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An alternate respiratory pathway in Candida albicans

Cited by 28 publications

References 24 publications

Contribution of a Cyanide-insensitive Alternate Respiratory System to Increases in Formamide Hydro-lyase Activity and to Growth in Stemphylium loti in Vitro

Contribution of a Cyanide-insensitive Alternate Respiratory System to Increases in Formamide Hydro-lyase Activity and to Growth in Stemphylium loti in Vitro

The Production of Reactive Oxygen Species Is a Universal Action Mechanism of Amphotericin B against Pathogenic Yeasts and Contributes to the Fungicidal Effect of This Drug

A Glucose Sensor in Candida albicans

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