1887

Abstract

SUMMARY

A peptide transport gene, , was cloned from a genomic library by functional complementation of a peptide transport deficient mutant (strain 2-2) of restored peptide transport to transformants as determined by uptake of radiolabelled dileucine, growth on dipeptides as sources of required amino acids, and restoration of growth inhibition by toxic peptides. Plasmid curing experiments demonstrated that the peptide transport phenotype was plasmid borne. was localized to chromosome R of by contour-clamped homologous electric field gel chromosome blots. Deletion subclones and frameshift mutagenesis were used to narrow the peptide transport complementing region to a 5:1 kb DNA fragment. DNA sequencing of the complementing region identified an ORF of 1869 bp containing an 84 nucleotide intron. The deduced amino acid sequence predicts a protein of 70 kDa consisting of 623 amino acids with 12 hydrophobic segments. A high level of identity was found between the predicted protein and peptide transport proteins of and This study represents the first steps in the genetic characterization of peptide transport in and initiates a molecular approach for the study of drug delivery against this pathogen.

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1995-05-01
2021-05-17
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References

  1. Alagramam K., Naider F., Becker J.M. 1995; A recognition component of the ubiquitin system is required for peptide transport inSaccharomyces cerevisiae. . Mol Microbiol 15:225–234
    [Google Scholar]
  2. Altboum Z., Gottlieb S., Lebens G.A., Polacheck I., Segal E. 1990; Isolation of theCandida albicans histidinol dehydrogenase(HIS4) gene and characterization of a histidine auxotroph.. J Bacteriol 172:3898–3904
    [Google Scholar]
  3. Altshul S.F., Gish W., Miiler W., Myers E.W., Lipman D.J. 1990; Basic local alignment search tool.. J Mol Biol 215:403–410
    [Google Scholar]
  4. Ames B.N., Ferro-Luzzi Ames G., Young J.D., Tsuchiya D., Lecocq J. 1973; Illicit transport: the oligopeptide permease.. Proc Natl Acad Sci USA 70:456–458
    [Google Scholar]
  5. Ausubei F.M., Brent R., Kingston R., Moore D.D., Seidman J.G., Smith J.A., Struhl K. 1990 Current Protocols in Molecular Biology 2: New York:: Wiley Interscience.;
    [Google Scholar]
  6. Bartel B., Wunning I., Varshavsky A. 1990; The recognition component of the N-end rule pathway.. EMBO J 9:3179–3189
    [Google Scholar]
  7. Basrai M.A., Zhang H.-L, Miller D, Naider F., Becker J.M. 1992; Toxicity of oxalysine and oxalysine-containing peptides againstCandida albicans-, regulation of peptide transport by amino acids.. J Gen Microbiol 138:2353–2362
    [Google Scholar]
  8. Becker J.M., Naider F. 1977; Peptide transport in yeast: uptake of radioactive trimethionine inSaccharomyces cerevisiae. . Arch Biochem Biophys 178:245–255
    [Google Scholar]
  9. Becker J.M., Naider F. 1980; Transport and utilization of peptides by yeast.. In Transport and Utilization of Amino Acids, Peptides and Proteins by Microorganisms, pp. 257–279 Payne. J. W. Edited by London:: John Wiley.;
    [Google Scholar]
  10. Becker J.M., Naider F. 1995; Fungal peptide transport as a drug delivery system.. In Peptide Based Drug Design: Controlling Transport and Metabolism, pp. 369–384 Taylor M., Amidon. G. Edited by Washington, DC:: American Chemical Society.;
    [Google Scholar]
  11. Ben-Yaacov R., Knoller S., Caldwell G.A., Becker J.M., Koitin Y. 1994; Candida albicans gene encoding resistance to benomyl and methotrexate is a multidrug resistance gene.. Antimicrob Agents Chemother 38:648–652
    [Google Scholar]
  12. Cabib E. 1991; Differential inhibition of chitin synthetases 1 and 2 fromSaccharomyces cerevisiae by polyoxin D and nikkomycins.. Antimicrob Agents Chemother 35:170–173
    [Google Scholar]
  13. Chambers R.S., Broughton M.J., Cannon R.D., Came A., Emerson G.W., Sullivan P.A. 1993; An exo-β-(l,3)-glucanase ofCandida albicans: purification of the enzyme and molecular cloning of the gene.. J Gen Microbiol 139:325–334
    [Google Scholar]
  14. Devereux J., Haeberli P., Smithies O. 1984; A comprehensive set of sequence analysis programs for the VAX.. Nucleic Acids Res 12:387–395
    [Google Scholar]
  15. Fei Y.-J., Kanai Y., Nussberger S., Ganapathy V., Leibach F.H., Romero M.F., Singh S.K., Boron W.F., Hediger M.A. 1994; Expression cloning of a mammalian proton-coupled oligopeptide transporter.. Nature 368:563–566
    [Google Scholar]
  16. Feng D.-F., Doolittle R.F. 1987; Progressive sequence alignment as a prerequisite to correct phylogenetic trees.. J Mol Evol 25:351–360
    [Google Scholar]
  17. Fickel T.E., Gilvarg C. 1973; Transport of impermeant substances inEscherichia coli by way of oligopeptide permease.. Nature 241:161–163
    [Google Scholar]
  18. Gietz D., Andrew J., Woods R., SchiestI R. 1991; Improved methods for high efficiency transformation of intact yeast cells.. Nucleic Acids Res 20:1425
    [Google Scholar]
  19. Grenson M. 1992; Amino acid transporters in yeast: structure. function and regulation.. In Molecular Aspects of Transport Proteins, pp. 219–245 De Pont. J. J. H. H. M. Edited by Amsterdam:: Elsevier;
    [Google Scholar]
  20. Hammond S.M., Claesson A., Jansson A.M., Larsson L-G., Pring B.G., Town C.M., Ekstrom B. 1987; A new class of synthetic antibacterials acting on lipopolysaccharide biosynthesis.. Nature 327:730–732
    [Google Scholar]
  21. Higgins C.F. 1987; Synthesizing designer drugs.. Nature 327:655–656
    [Google Scholar]
  22. Higgins C.F. 1992; ABC transporters: from microorganisms to man.. Annu Rev Cell Biol 8:67–113
    [Google Scholar]
  23. Hiles I.D., Gallagher M.P., Jamieson D.J., Higgins C.F. 1987; Molecular characterization of the oligopeptide permease ofSalmonella tjphimurium. . J Mol Biol 195:125–142
    [Google Scholar]
  24. Innis M.A., Gelfand D.H. 1990; Optimizations of PCR.. In PCR Protocols: a Guide to Methods and Applications, pp. 3–12 Innis M. A., Gelfald D. H., Sninsky J. J., T. J. White. New York:: Academic Press.;
    [Google Scholar]
  25. Island M.D., Naider F., Becker J.M. 1987; Regulation of dipeptide transport inSaccharomjces cerevisiae by micromolar amino acid concentrations.. J Bacteriol 169:2132–2136
    [Google Scholar]
  26. Island M.D., Perry J.R., Naider F., Becker J.M. 1991; Isolation and characterization of S.cerevisiae mutants deficient in amino acid-inducible peptide transport.. Curr Genetics 20:457–463
    [Google Scholar]
  27. Kelly R., Miller S.M., Kurtz M.B., Kirsch D.R. 1987; Directed mutagenesis inCandida albicans: one step gene disruption to isolateUR A3 mutants.. Mol Cell Bioll,199–207
    [Google Scholar]
  28. Kelly R., Miller S.M., Lai M.H., Kirsch D.R. 1990; Cloning and characterization of the 2,3-oxidosqualene cyclase-encoding gene ofCandida albicans. . Gene 87:177–183
    [Google Scholar]
  29. Kirsch D.R., Lai M.H., O'Sullivan J. 1988; Isolation of the gene for cytochrome P450 LlAl (lanosterol 14 alpha-demethylase) fromCandida albicans. . Gene 68:229–237
    [Google Scholar]
  30. Kuchler K., Sterne R.E., Thorner J. 1989; Saccharomjces cerevisiae STE6 gene product: a novel pathway for protein export in eukaryotic cells.. EMBO J 8:3973–3984
    [Google Scholar]
  31. Kurtz M.B., Kelly R., Kirsch D.R. 1990; Molecular genetics ofCandida albicans. . In The Genetics of Candida, pp. 21–73 Kirsch D. R., Kelly R., Kurtz. M.B. Edited by Boca Raton, FL:: CRC Press.;
    [Google Scholar]
  32. McCarthy J.P., Nisbet LJ., Boehm J.C., Kingsbury W.D. 1985; Multiplicity of peptide permeases inCandida albicans:evidence from novel chromophoric peptides.. J Bacteriol 162:1024–1029
    [Google Scholar]
  33. McCombie W.R., Heiner C., Kelley J.M., Fitzgerald M.G., Gocayne J.D. 1992; Rapid and reliable fluorescent cycle sequencing of double stranded templates.. DNA Seq 2:289–296
    [Google Scholar]
  34. McGrath J.P., Varshavsky A. 1989; The yeastSTE6 gene encodes a homologue of the mammalian multidrug resistance P- glycoprotein.. Nature 340:400–404
    [Google Scholar]
  35. Matthews D.M. 1991 Protein Absorption: Development and Present State of the Subject. New York:: Wiley-Liss.;
    [Google Scholar]
  36. Naider F., Becker J. M. 1987; Peptide transport inCandida albicans: implications for the development of antifungal agents.. Curr Top Med Mjcol 2:170–198
    [Google Scholar]
  37. Naider F., Shenbagamurthi P., Steinfeld A.S., Smith H.A., Boney C., Becker J.M. 1983; Synthesis and biological activity of tripeptidyl polyoxins as antifungal agents.. Antimicrob Agents Chemother 24:787–796
    [Google Scholar]
  38. Payne J.W. 1980; Transport and utilization of peptides by bacteria.. In Microorganisms and Nitrogen Sources, pp. 211–256 Payne. J. W. Edited by New York:: John Wiley;
    [Google Scholar]
  39. Payne J.W., Barrett-Bee K.J., Shallow D.A. 1991; Peptide substrates rapidly modulate expression of dipeptide and oligopeptide permeases inCandida albicans. . FEMS Microbiol Lett 79:15–20
    [Google Scholar]
  40. Perry J.R., Basrai M.A., Steiner H.-Y., Naider F., Becker J.M. 1994; Isolation and characterization of aSaccharomjces cerevisiaepeptide transport gene.. Mol Cell Biol 14:104–115
    [Google Scholar]
  41. Rai R., Genbauffe F.S., Cooper T.G. 1988; Structure and transcription of the allonantoate permease gene (DAL5) fromSaccharomjces cerevisiae. . J Bacteriol 170:266–271
    [Google Scholar]
  42. Rymond B.C., Rosbash M. 1992; Yeast pre-mRNA splicing.. In The Molecular and Cellular Biology of the Yeast Saccharomjces, pp. 143–192 Jones E. W., Pringle J. R., Broach. J. R. Edited by Cold Spring Harbor, NY:: Cold Spring Harbor Laboratory.;
    [Google Scholar]
  43. Sambrook J., Fritsch E.F., Maniatis T. 1989 Molecular Cloning: a Laboratorj Manual,, 2nd. Cold Spring Harbor, NY:: Cold Spring Harbor Laboratory.;
    [Google Scholar]
  44. Scherer S., Magee P.T. 1990; Genetics ofCandida albicans. . Microbiol Rev 54:226–241
    [Google Scholar]
  45. Sherman F., Fink G.R., Hicks J.B. 1986 Methods of Yeast Genetics. Cold Spring Harbor, NY:: Cold Spring Harbor Laboratory.;
    [Google Scholar]
  46. Sikorski R.S., Hieter P.H. 1989; A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA inSaccharomjces cerevisiae. . Genetics 122:19–27
    [Google Scholar]
  47. Smith L.M., Sander J.Z., Kaiser R.J., Hughes P., Dodd C., Connel C.R., Heiner C, Kent S.B, Hood LE. 1986; Fluorescence detection in automated DNA sequence analysis.. Nature 321:674–679
    [Google Scholar]
  48. Steiner H.-Y., Song W., Naider F., Zhang L., Stacey G., Becker J.M. 1994; AnArabidopsis peptide transporter is a member of a new class of membrane transport proteins.. Plant Cell 6:1289–1299
    [Google Scholar]
  49. Wickes B., Staudinger J., Magee B.B., Kwon-Chung K.J., Magee P.T., Scherer S. 1991; Physical and genetic mapping ofCandida albicans: several genes previously assigned to chromosome 1 map to chromosome R, the rDNA containing linkage group.. Infect Immun 59:2480–2484
    [Google Scholar]
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