A Tale of Two Biofilms
Autor: | Kevin L. Lu, Nidhi Sahni, Guanghua Huang, Adam M. Garnaas, Song Yi, Thyagarajan Srikantha, David R. Soll, Karla J. Daniels |
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Rok vydání: | 2011 |
Předmět: |
MAPK/ERK pathway
Mating type Antifungal Agents MAP Kinase Signaling System Neutrophils QH301-705.5 Biology Permeability General Biochemistry Genetics and Molecular Biology Microbiology Fungal Proteins Antibiotic resistance Drug Resistance Fungal Candida albicans Cyclic AMP Humans Phosphorylation Biology (General) Fluconazole Regulation of gene expression Fungal protein General Immunology and Microbiology General Neuroscience Biofilm Genes Mating Type Fungal biology.organism_classification Corpus albicans Cell biology DNA-Binding Proteins Biofilms Sex pheromone Synopsis ras Proteins cAMP-dependent pathway Medicine Signal transduction General Agricultural and Biological Sciences Transcription Factors Research Article |
Zdroj: | PLoS Biology PLoS Biology, Vol 9, Iss 8, p e1001117 (2011) PLoS Biology, Vol 9, Iss 8, p e1001119 (2011) |
ISSN: | 1545-7885 |
Popis: | 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. Author Summary Single-celled microbes can form biofilms, or aggregates of cells that adhere to one another on a surface, in response to many environmental factors. Like many microbial pathogens, the yeast Candida albicans can form biofilms that normally provide protective environments against antifungals, antibodies, and white blood cells, thus ensuring higher rates of survival in response to assault by drugs or the human immune system. We report that while a majority (around 90%) of C. albicans strains form traditional biofilms that are impermeable to molecules of low and high molecular weight, and that are impenetrable to white blood cells, a minority (around 10%) form biofilms that are both permeable and penetrable. Formation of the minority-type alternative biofilms is dictated by a change at a single genetic locus, the mating type locus. Homozygous a/a or α/α cells are mating-competent, whereas the heterozygous a/α cells are mating-incompetent. Cells of the mating-incompetent a/α genotype form the impermeable, traditional biofilm, whereas the mating-competent a/a or α/α genotype forms the permeable biofilm. The characteristics of a/a and α/α biofilms are consistent with a suggested role in mating by facilitating the transfer of hormone signals through the permeable biofilm. The two types of biofilm are also regulated by different signal transduction pathways: the a/α form by the Ras1/cAMP pathway, and the a/a or α/α forms by the MAP kinase pathway. Components of the latter pathway suggest that its downstream portion evolved from the a/α pathway. C. albicans, therefore, forms two superficially similar biofilms, exhibiting very different permeability characteristics, regulated by different signal transduction pathways, dictated by different mating type locus configurations, and serving quite different purposes in its life history. |
Databáze: | OpenAIRE |
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