Peptide Transport in Candida albicans

Logan, David A.; Becker, Jeffrey M.; Naider, Fred

doi:10.1099/00221287-114-1-179

Cited by 35 publications

(33 citation statements)

References 11 publications

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“…Also, we observed increased growth of ilv2 mutants when minimal, dipeptide-supplemented medium contained proline as the nitrogen source instead of ammonium. These results indicate that, like transport of isoleucine and/or valine by this strain and dipeptide transport by S. cerevisiae (Becker & Naider, 1977;Nisbet & Payne, 1979) and C. albicans (Logan et al, 1979;Payne et al, 1991), C. neoformans dipeptide transport may also be regulated by nitrogen source.…”

Section: Discussionmentioning

confidence: 82%

Cryptococcus neoformans Ilv2p confers resistance to sulfometuron methyl and is required for survival at 37 °C and in vivo

et al. 2004

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Acetolactate synthase catalyses the first common step in isoleucine and valine biosynthesis and is the target of several classes of inhibitors. The Cryptococcus neoformans ILV2 gene, encoding acetolactate synthase, was identified by complementation of a Saccharomyces cerevisiae ilv2 mutant. C. neoformans is highly resistant to the commercially available acetolactate synthase inhibitor, sulfometuron methyl (SM). Expression of C. neoformans ILV2 in S. cerevisiae conferred SM resistance, indicating that the SM resistance of C. neoformans is due, at least in part, to C. neoformans Ilv2p. The C. neoformans ILV2 gene was disrupted. The ilv2 mutants were auxotrophic for isoleucine and valine and the auxotrophy was satisfied by these amino acids only when proline, and not ammonium, was the nitrogen source, indicating nitrogen regulation of amino acid transport. ilv2 mutants rapidly lost viability at 37 °C and when starved for isoleucine and valine. Consistent with these phenotypes, an ilv2 mutant was avirulent and unable to survive in mice. Because C. neoformans Ilv2p is required for virulence and survival in vivo, inhibitors of branched-chain amino acid biosynthesis may make valuable antifungal agents.

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Section: Discussionmentioning

confidence: 82%

Cryptococcus neoformans Ilv2p confers resistance to sulfometuron methyl and is required for survival at 37 °C and in vivo

et al. 2004

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“…Oxalysinecontaining di-and tripeptides were only weakly toxic in medium containing ammonium sulphate in contrast to the other nitrogen sources. Ammonium sulphate is known to be a repressive nitrogen source for peptide transport in C. albicans (Logan et al, 1979). The influence of the nitrogen source on the toxicity of tetraand pentapeptides was minor, with both repressive and non-repressive nitrogen metabolites resulting in similar zones of inhi bition.…”

Section: Eflect Oj'nitrogen Source On the Toxicity Of Oxalysine And Omentioning

confidence: 93%

“…albicans (Becker & Naider, 1977Logan et al, 1979;Nisbet & Payne, 1979;McCarthyet al, 1985a;Moneton et al, 1986a, b ;Payne & Shallow, 1985;Payne et al, 1991 ;Yadan et al, 1984). C. albicans can utilize various organic compounds, such as isoleucine, proline, allantoin and peptone as a sole source of nitrogen.…”

Section: Eflect Oj'nitrogen Source On the Toxicity Of Oxalysine And Omentioning

confidence: 99%

“…albicans is regulated by nitrogen metabolism (Becker & Naider, 1977Davies, 1980;McCarthy et al, 1985a, b;Payne et al, 1991 ;Yadan et al, 1984). For example, peptide uptake is repressed by ammonium ions and stimulated when cells are grown on amino acids as the sole nitrogen source (Logan et al, 1979). Recently, Payne et al (1991) reported stimulation of dialanine transport in C. albicans B2630grown in media containing bactopeptone or trypticase peptone but not casein hydrolysate.…”

Section: Introductionmentioning

confidence: 99%

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Toxicity of oxalysine and oxalysine-containing peptides against Candida albicans: regulation of peptide transport by amino acids

Basrai

Zhang

Miller

et al. 1992

Journal of General Microbiology

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A lysine antimetabolite, L-4-oxalysine [ H2NCH2CH20CH2CH(NH2)COOH], and oxalysine-containing di-, tri-, tetra-and pentapeptides inhibited growth of Candidu albicans H317. Micromolar amounts of amino acids were found to overcome ammonium repression of the di-and tripeptide transport system(s) in strain H317. Several amino acids increased the toxicity of oxalysine-containing di-and tripeptides for C. albicans with little or no increase in toxicity of oxalysine or oxalysine-containing tetra-and pentapeptides. L-Lysine completely reversed the toxicity of oxalysine by competing with the transport of oxalysine into the cells. In contrast, L-lysine increased the toxicity of oxalysine-containing di-and tripeptides, but had no effect on the toxicity of oxalysine-containing tetra-and pentapeptides. Incubation of cells with L-lysine for 4 h resulted in a 15-fold increase in the rate of transport of radiolabelled dileucine, indicating that increased sensitivity of C. ufbicans to some toxic peptides in the presence of L-lysine may be attributed to an increased rate of transport of these peptides. Our results indicate that the dipeptide and tripeptide transport system(s) of C. ulbicuns are regulated by micromolar amounts of amino acids in a similar fashion to the regulation of peptide transport in Succhuromyces cerevisiue and that multiple peptide transport systems differentially regulated by various nitrogen sources and amino acids exist in C. ulbicuns.

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“…It was determined that the dipeptide glycyl DL-valine antagonized the in vivo activity of the biologically active polyoxin B compound, yet had no inhibitory action in the cell-free chitin synthetase assay system (119,164). This led Hori et (151).…”

Section: Compounds Active Against Fungal Cell Walls Inhibitors Of Chimentioning

confidence: 99%

Compounds active against cell walls of medically important fungi

Hector

1993

Clin Microbiol Rev

217

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A number of substances that directly or indirectly affect the cell walls of fungi have been identified. Those that actively interfere with the synthesis or degradation of polysaccharide components share the property of being produced by soil microbes as secondary metabolites. Compounds specifically interfering with chitin or beta-glucan synthesis have proven effective in studies of preclinical models of mycoses, though they appear to have a restricted spectrum of coverage. Semisynthetic derivatives of some of the natural products have offered improvements in activity, toxicology, or pharmacokinetic behavior. Compounds which act on the cell wall indirectly or by a secondary mechanism of action, such as the azoles, act against diverse fungi but are usually fungistatic in nature. Overall, these compounds are attractive candidates for further development.

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Peptide Transport in Candida albicans

Abstract: 179The tripeptide L-methionyl-L-methionyl-L-[methyZ-14C]methionine was taken up into Candida albicans by a saturable system with a pH optimum of 3.5, a temperature optimum of 37 "C and an apparent K, of 3.

Cited by 35 publications

References 11 publications

Cryptococcus neoformans Ilv2p confers resistance to sulfometuron methyl and is required for survival at 37 °C and in vivo

Cryptococcus neoformans Ilv2p confers resistance to sulfometuron methyl and is required for survival at 37 °C and in vivo

Toxicity of oxalysine and oxalysine-containing peptides against Candida albicans: regulation of peptide transport by amino acids

Compounds active against cell walls of medically important fungi

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