title: TUP1 disruption in Cryptococcus neoformans uncovers a peptide-mediated density-dependent growth phenomenon that mimics quorum sensing.
abstract: Cryptococcus neoformans is a pathogenic yeast that causes life-threatening meningoencephalitis and grows well on mycological media regardless of inoculum size. Interestingly, a deletion of the global repressor TUP1 in C. neoformans uncovered a density-dependent growth phenotype reminiscent of the quorum-sensing phenomenon. An inoculum size of lower than 10(3) cells of the tup1Delta strain failed to form colonies on agar media while inocula of 10(5)-10(6) cells per plate formed a lawn. This phenotype, expressed as the inability to grow at low cell densities, was rescued by the culture filtrate from a high cell density tup1Delta culture and the active molecule in this culture filtrate was identified to be an oligopeptide composed of 11 amino acids. Activity assays, using a synthetic version of the peptide with strains harbouring a deletion of the corresponding gene, proved that the oligopeptide functioned as an autoregulatory molecule responsible for the density-dependent phenotype. Although a density-dependent growth phenotype has been reported in several species of Ascomycetes, no peptide has been reported to function as an autoregulator in the Kingdom Fungi. The identification of an 11-mer peptide as an autoregulatory molecule in C. neoformans suggests that a diverse mechanism of cell-to-cell communication exists in the Kingdom Fungi.
authors.affiliation: Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
authors.forename: Hyeseung
authors.initials: H
authors.lastname: Lee
authors.forename: Yun C
authors.initials: YC
authors.lastname: Chang
authors.forename: Glenn
authors.initials: G
authors.lastname: Nardone
authors.forename: Kyung J
authors.initials: KJ
authors.lastname: Kwon-Chung
mesh_terms: D000595:Amino Acid Sequence; D003455:Cryptococcus neoformans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D003470:Culture Media / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D015870:Gene Expression / Q000187:drug effects; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000502:physiology*; D016133:Polymerase Chain Reaction; D053038:Quorum Sensing / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology
chemical_list: D003470:Culture Media; D005656:Fungal Proteins; D010455:Peptides; D012097:Repressor Proteins