title: Alternative mating type configurations (a/α versus a/a or α/α) of Candida albicans result in alternative biofilms regulated by different pathways.
abstract: Similar multicellular structures can evolve within the same organism that may have different evolutionary histories, be controlled by different regulatory pathways, and play similar but nonidentical roles. In the human fungal pathogen Candida albicans, a quite extraordinary example of this has occurred. Depending upon the configuration of the mating type locus (a/α versus a/a or α/α), C. albicans forms alternative biofilms that appear similar morphologically, but exhibit dramatically different characteristics and are regulated by distinctly different signal transduction pathways. Biofilms formed by a/α cells are impermeable to molecules in the size range of 300 Da to 140 kDa, are poorly penetrated by human polymorphonuclear leukocytes (PMNs), and are resistant to antifungals. In contrast, a/a or α/α biofilms are permeable to molecules in this size range, are readily penetrated by PMNs, and are susceptible to antifungals. By mutational analyses, a/α biofilms are demonstrated to be regulated by the Ras1/cAMP pathway that includes Ras1→Cdc35→cAMP(Pde2-|)→Tpk2(Tpk1)→Efg1→Tec1→Bcr1, and a/a biofilms by the MAP kinase pathway that includes Mfα→Ste2→ (Ste4, Ste18, Cag1)→Ste11→Hst7→Cek2(Cek1)→Tec1. These observations suggest the hypothesis that while the upstream portion of the newly evolved pathway regulating a/a and α/α cell biofilms was derived intact from the upstream portion of the conserved pheromone-regulated pathway for mating, the downstream portion was derived through modification of the downstream portion of the conserved pathway for a/α biofilm formation. C. albicans therefore forms two alternative biofilms depending upon mating configuration.
authors.affiliation: Department of Biology, The University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Song
authors.initials: S
authors.lastname: Yi
authors.forename: Nidhi
authors.initials: N
authors.lastname: Sahni
authors.forename: Karla J
authors.initials: KJ
authors.lastname: Daniels
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Lu
authors.forename: Thyagarajan
authors.initials: T
authors.lastname: Srikantha
authors.forename: Guanghua
authors.initials: G
authors.lastname: Huang
authors.forename: Adam M
authors.initials: AM
authors.lastname: Garnaas
authors.forename: David R
authors.initials: DR
authors.lastname: Soll
mesh_terms: D000935:Antifungal Agents; D018441:Biofilms; D002176:Candida albicans / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D025141:Drug Resistance, Fungal / Q000235:genetics*; D015725:Fluconazole; D005656:Fungal Proteins / Q000378:metabolism; D049770:Genes, Mating Type, Fungal; D006801:Humans; D020935:MAP Kinase Signaling System; D009504:Neutrophils / Q000502:physiology*; D010539:Permeability; D010766:Phosphorylation; D014157:Transcription Factors / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D004268:DNA-Binding Proteins; C121438:EFG1 protein, Candida albicans; D005656:Fungal Proteins; C489432:TEC1 protein, Candida albicans; D014157:Transcription Factors; D015725:Fluconazole; D000242:Cyclic AMP; D018631:ras Proteins