Alternative mating type configurations (a/α versus a/a or α/α) of candida albicans result in alternative biofilms regulated by different pathways

Song Yi, Nidhi Sahni, Karla J. Daniels, Kevin L. Lu, Thyagarajan Srikantha, Guanghua Huang, Adam M. Garnaas, David R. Soll

Research output: Contribution to journalArticle

65 Citations (Scopus)

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-{pipe})→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.

Original languageEnglish
Article numbere1001117
JournalPLoS Biology
Volume9
Issue number8
DOIs
StatePublished - 1 Aug 2011

Fingerprint

Candida
Biofilms
Candida albicans
biofilm
Signal transduction
Molecules
mating types
Pheromones
Pathogens
pipes
mitogen-activated protein kinase
pheromones
signal transduction
neutrophils
Signal Transduction
Neutrophils
Phosphotransferases
Pipe
cells
history

Cite this

Yi, Song ; Sahni, Nidhi ; Daniels, Karla J. ; Lu, Kevin L. ; Srikantha, Thyagarajan ; Huang, Guanghua ; Garnaas, Adam M. ; Soll, David R. / Alternative mating type configurations (a/α versus a/a or α/α) of candida albicans result in alternative biofilms regulated by different pathways. In: PLoS Biology. 2011 ; Vol. 9, No. 8.
@article{b516d34ce45f489c80c18d2b6e519990,
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-{pipe})→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 = "Song Yi and Nidhi Sahni and Daniels, {Karla J.} and Lu, {Kevin L.} and Thyagarajan Srikantha and Guanghua Huang and Garnaas, {Adam M.} and Soll, {David R.}",
year = "2011",
month = "8",
day = "1",
doi = "10.1371/journal.pbio.1001117",
language = "English",
volume = "9",
journal = "PLoS Biology",
issn = "1544-9173",
publisher = "Public Library of Science",
number = "8",

}

Alternative mating type configurations (a/α versus a/a or α/α) of candida albicans result in alternative biofilms regulated by different pathways. / Yi, Song; Sahni, Nidhi; Daniels, Karla J.; Lu, Kevin L.; Srikantha, Thyagarajan; Huang, Guanghua; Garnaas, Adam M.; Soll, David R.

In: PLoS Biology, Vol. 9, No. 8, e1001117, 01.08.2011.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Alternative mating type configurations (a/α versus a/a or α/α) of candida albicans result in alternative biofilms regulated by different pathways

AU - Yi, Song

AU - Sahni, Nidhi

AU - Daniels, Karla J.

AU - Lu, Kevin L.

AU - Srikantha, Thyagarajan

AU - Huang, Guanghua

AU - Garnaas, Adam M.

AU - Soll, David R.

PY - 2011/8/1

Y1 - 2011/8/1

N2 - 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-{pipe})→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.

AB - 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-{pipe})→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.

UR - http://www.scopus.com/inward/record.url?scp=80052318532&partnerID=8YFLogxK

U2 - 10.1371/journal.pbio.1001117

DO - 10.1371/journal.pbio.1001117

M3 - Article

C2 - 21829325

AN - SCOPUS:80052318532

VL - 9

JO - PLoS Biology

JF - PLoS Biology

SN - 1544-9173

IS - 8

M1 - e1001117

ER -