Differential effect of the alkaloid lycorine on rho +, mit +, rho -, and rho° strains of Saccharomyces cerevisiae

Giudice, Luigi Del; Massardo, Domenica Rita; Manna, F.; Evidente, A.; Randazzo, G.; Wolf, Kurt

doi:10.1007/bf00436969

Cited by 5 publications

(11 citation statements)

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“…Interestingly, petite mutations are associated with a decreased susceptibility of yeasts to various chemicals, such as tannic acid or the alkaloid lycorine (7,37). Likewise, Gyurko et al (11) recently demonstrated that respiration-deficient mutants of C. albicans were resistant to histatin 5, a small cationic salivary antimicrobial peptide, mitochondrial ATP synthesis being required for effective killing activity of this salivary peptide.…”

Section: Influence Of Respiratory Chain Inhibitors (I) Oxygen Consummentioning

confidence: 99%

Relationships between Respiration and Susceptibility to Azole Antifungals in Candida glabrata

Brun¹,

Aubry²,

Lima

et al. 2003

Antimicrob Agents Chemother

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Over the past two decades, the incidence of infections due to Candida glabrata, a yeast with intrinsic low susceptibility to azole antifungals, has increased markedly. Respiratory deficiency due to mutations in mitochondrial DNA (mtDNA) associated with resistance to azoles frequently occurs in vitro in this species. In order to specify the relationships between respiration and azole susceptibility, the effects of respiratory chain inhibitors on a wild-type isolate of C. glabrata were evaluated. Respiration of blastoconidia was immediately blocked after extemporaneous addition of potassium cyanide, whereas a 4-h preincubation was required for sodium azide. Antifungal susceptibility determined by a disk diffusion method on Casitone agar containing sodium azide showed a significant decrease in the susceptibility to azoles. Biweekly subculturing on Casitone agar supplemented with sodium azide was therefore performed. This resulted after 40 passages in the isolation of a respiration-deficient mutant, as suggested by its lack of growth on glycerol-containing agar. This respiratory deficiency was confirmed by flow cytometric analysis of blastoconidia stained with rhodamine 123 and by oxygraphy. Moreover, transmission electron microscopy and restriction endonuclease analysis of the mtDNA of mutant cells demonstrated the mitochondrial origin of the respiratory deficiency. Finally, this mutant exhibited cross-resistance to all the azoles tested. In conclusion, blockage of respiration in C. glabrata induces decreased susceptibility to azoles, culminating in azole resistance due to the deletion of mtDNA. This mechanism could explain the induction of petite mutations by azole antifungals which have been demonstrated to act directly on the mitochondrial respiratory chain.

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Section: Influence Of Respiratory Chain Inhibitors (I) Oxygen Consummentioning

confidence: 99%

Relationships between Respiration and Susceptibility to Azole Antifungals in Candida glabrata

Brun¹,

Aubry²,

Lima

et al. 2003

Antimicrob Agents Chemother

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“…In previous papers we have demonstrated that lycorine inhibits growth of rho + , rho À and mit À strains, whereas rho 0 strains (devoid of mtDNA) of S. cerevisiae are resistant to high concentrations of the drug (Del Giudice et al, 1984;Massardo et al, 2000). In a search for new genes whose expression is RTGdependent in mitochondria to nucleus signaling we have analyzed the growth of isogenic rho 0 Drtg strains with different doses of lycorine.…”

Section: Discussionmentioning

confidence: 98%

“…Thus, neither respiration nor mitochondrial protein synthesis are responsible for the differential effect of lycorine (Del Giudice et al, 1984).…”

Section: Effect Of Lycorine On Macromolecular Synthesesmentioning

confidence: 88%

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Interaction between yeast mitochondrial and nuclear genomes: Null alleles of RTG genes affect resistance to the alkaloid lycorine in rho0 petites of Saccharomyces cerevisiae

Giudice¹,

Massardo²,

Pontieri³

et al. 2005

Gene

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“…Wild-type rho + cells, neutral rho -cells, and moderately suppressive rho -cells are all sensitive to the lycorine; rho 0 cells, however, are resistant to high concentration of the drug (Del Giudice et al 1984). Most hyper-suppressive rho -strains show an intermediate resistance to lycorine (Massardo et al 1990).…”

Section: Introductionmentioning

confidence: 98%

Use of lycorine and DAPI staining inSaccharomyces cerevisiaeto differentiate betweenrho⁰andrho^-cells in acce1/Δcce1 nuclear background

Massardo

Zweifel²,

Gunge³

et al. 2000

Can. J. Microbiol.

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In the yeast Saccharomyces cerevisiae, mutants are viable with large deletions (rho-), or even complete loss of the mitochondrial genome (rho0). One class of rho- mutants, which is called hypersuppressive, is characterised by a high transmission of the mutated mitochondrial genome to the diploid progeny when mated to a wild-type (rho+) haploid. The nuclear gene CCE1 encodes a cruciform cutting endonuclease, which is located in the mitochondrion and is responsible for the highly biased transmission of the hypersuppressive rho- genome. CCE1 is a Holliday junction specific endonuclease that resolves recombination intermediates in mitochondrial DNA. The cleavage activity shows a strong preference for cutting after a 5'-CT dinucleotide. In the absence of the CCE1 gene product, the mitochondrial genomes remain interconnected and have difficulty segregating to the daughter cells. As a consequence, there is an increase in the fraction of daughter cells that are rho0. In this paper we demonstrate the usefulness of lycorine, together with staining by 4',6-diamidino-2-phenylindole (DAPI), to assay for the mitotic stability of a variety of mitochondrial genomes. We have found that rho+ and rho- strains that contain CT sequences produce a large fraction of rho0 progeny in the absence of CCE1 activity. Only those rho- mitochondrial genomes lacking the CT recognition sequence are unaffected by the cce1 allele.

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Differential effect of the alkaloid lycorine on rho +, mit +, rho -, and rho° strains of Saccharomyces cerevisiae

Abstract: Due to an error in the preparation of Table 2, the figures in part B) and part C) are not in the right position. The corrected Table 2 now reads as follows:

Cited by 5 publications

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Relationships between Respiration and Susceptibility to Azole Antifungals in Candida glabrata

Relationships between Respiration and Susceptibility to Azole Antifungals in Candida glabrata

Interaction between yeast mitochondrial and nuclear genomes: Null alleles of RTG genes affect resistance to the alkaloid lycorine in rho0 petites of Saccharomyces cerevisiae

Use of lycorine and DAPI staining inSaccharomyces cerevisiaeto differentiate betweenrho⁰andrho^-cells in acce1/Δcce1 nuclear background

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Differential effect of the alkaloid lycorine on rho +, mit +, rho -, and rho° strains of Saccharomyces cerevisiae

Abstract: Due to an error in the preparation of Table 2, the figures in part B) and part C) are not in the right position. The corrected Table 2 now reads as follows:

Cited by 5 publications

References 0 publications

Relationships between Respiration and Susceptibility to Azole Antifungals in Candida glabrata

Relationships between Respiration and Susceptibility to Azole Antifungals in Candida glabrata

Interaction between yeast mitochondrial and nuclear genomes: Null alleles of RTG genes affect resistance to the alkaloid lycorine in rho0 petites of Saccharomyces cerevisiae

Use of lycorine and DAPI staining inSaccharomyces cerevisiaeto differentiate betweenrho0andrho-cells in acce1/Δcce1 nuclear background

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Use of lycorine and DAPI staining inSaccharomyces cerevisiaeto differentiate betweenrho⁰andrho^-cells in acce1/Δcce1 nuclear background