Title: | Alternative mating type configurations (a/alpha versus a/a or alpha/alpha) of Candida albicans result in alternative biofilms regulated by different pathways |
Author(s): | Yi S; Sahni N; Daniels KJ; Lu KL; Srikantha T; Huang G; Garnaas AM; Soll DR; |
Address: | "Department of Biology, The University of Iowa, Iowa City, Iowa, United States of America" |
DOI: | 10.1371/journal.pbio.1001117 |
ISSN/ISBN: | 1545-7885 (Electronic) 1544-9173 (Print) 1544-9173 (Linking) |
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/alpha versus a/a or alpha/alpha), 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/alpha 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 alpha/alpha biofilms are permeable to molecules in this size range, are readily penetrated by PMNs, and are susceptible to antifungals. By mutational analyses, a/alpha 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 Mfalpha-->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 alpha/alpha 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/alpha biofilm formation. C. albicans therefore forms two alternative biofilms depending upon mating configuration" |
Keywords: | "Antifungal Agents *Biofilms Candida albicans/*physiology Cyclic AMP/metabolism DNA-Binding Proteins/metabolism Drug Resistance, Fungal/*genetics Fluconazole Fungal Proteins/metabolism *Genes, Mating Type, Fungal Humans MAP Kinase Signaling System Neutroph;" |
Notes: | "MedlineYi, Song Sahni, Nidhi Daniels, Karla J Lu, Kevin L Srikantha, Thyagarajan Huang, Guanghua Garnaas, Adam M Soll, David R eng Research Support, N.I.H., Extramural 2011/08/11 PLoS Biol. 2011 Aug; 9(8):e1001117. doi: 10.1371/journal.pbio.1001117. Epub 2011 Aug 2" |