CO Acts as a Signalling Molecule in Populations of the Fungal Pathogen

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When colonising host-niches or non-animated medical devices, individual cells of the fungal pathogen Candida albicans expand into significant biomasses. Here we show that within such biomasses, fungal metabolically generated CO₂ acts as a communication molecule promoting the switch from yeast to filamentous growth essential for C. albicans pathology. We find that CO₂-mediated intra-colony signalling involves the adenylyl cyclase protein (Cyr1p), a multi-sensor recently found to coordinate fungal responses to serum and bacterial peptidoglycan. We further identify Lys 1373 as essential for CO₂/bicarbonate regulation of Cyr1p. Disruption of the CO₂/bicarbonate receptor-site interferes selectively with C. albicans filamentation within fungal biomasses. Comparisons between the Drosophila melanogaster infection model and the mouse model of disseminated candidiasis, suggest that metabolic CO₂ sensing may be important for initial colonisation and epithelial invasion. Our results reveal the existence of a gaseous Candida signalling pathway and its molecular mechanism and provide insights into an evolutionary conserved CO₂-signalling system.

Vyšlo v časopise: CO Acts as a Signalling Molecule in Populations of the Fungal Pathogen. PLoS Pathog 6(11): e32767. doi:10.1371/journal.ppat.1001193
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001193

Souhrn

Zdroje

1. AlmiranteB

RodríguezD

ParkBJ

Cuenca-EstrellaM

PlanesAM

2005 Epidemiology and Predictors of Mortality in Cases of Candida Bloodstream Infection: Results from Population-Based Surveillance, Barcelona, Spain, from 2002 to 2003. J Clin Microbiol 43 1829 1835

2. KlevayMJ

ErnstEJ

HollanbaughJL

MillerJG

PfallerMA

2008 Therapy and outcome of Candida glabrata versus Candida albicans bloodstream infection. Diag Microbiol Infect Dis 60 273 277

3. LeroyO

GangneuxJ-P

MontraversP

MiraJ-P

GouinF

2009 Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: A multicenter, prospective, observational study in France (2005–2006). Crit Care Med 37 1612 1618

4. BodeyGP

1986 Candidiasis in cancer patients. Am J Med 77 13 19

5. OddsFC

1988 Candida and candidosis A review and bibliography

6. ScullyC

el-KabirM

SamaranayakeL

1994 Candida and oral candidosis: a review. Crit Rev Oral Biol Med 5 125 157

7. FarahC

AshmanR

ChallacombeS

2000 Oral Candidosis. Clin Dermatol 18 553 562

8. LoH-J

KöhlerJR

DiDomenicoB

LoebenbergD

CacciapuotiA

1997 Nonfilamentous C. albicans Mutants Are Avirulent. Cell 90 939 949

9. SavilleSP

LazzellAL

MonteagudoC

Lopez-RibotJL

2003 Engineered Control of Cell Morphology In Vivo Reveals Distinct Roles for Yeast and Filamentous Forms of Candida albicans during Infection. Eukaryotic Cell 2 1053 1060

10. KlengelT

LiangW-J

ChaloupkaJ

RuoffC

SchroppelK

2005 Fungal Adenylyl Cyclase Integrates CO2 Sensing with cAMP Signaling and Virulence. Curr Biol 15 2021 2026

11. BuffoJ

HermanM

SollD

1984 A characterization of pH regulated dimorphism in Candida albicans. Mycopathologia 85 21 30

12. RochaCRC

SchroppelK

HarcusD

MarcilA

DignardD

2001 Signaling through Adenylyl Cyclase Is Essential for Hyphal Growth and Virulence in the Pathogenic Fungus Candida albicans. Mol Biol Cell 12 3631 3643

13. KamenetskyM

MiddelhaufeS

BankEM

LevinLR

BuckJ

2006 Molecular Details of cAMP Generation in Mammalian Cells: A Tale of Two Systems. J Mol Biol 362 623 639

14. VerstrepenKJ

KlisFM

2006 Flocculation, adhesion and biofilm formation in yeasts. Mol Microbiol 60 5 15

15. FangH-M

WangY

2006 RA domain-mediated interaction of Cdc35 with Ras1 is essential for increasing cellular cAMP level for Candida albicans hyphal development. Mol Microbiol 61 484 496

16. XuX-L

LeeRTH

FangH-M

WangY-M

LiR

2008 Bacterial Peptidoglycan Triggers Candida albicans Hyphal Growth by Directly Activating the Adenylyl Cyclase Cyr1p. Cell Host & Microbe 4 28 39

17. HoganDA

2006 Talking to Themselves: Autoregulation and Quorum Sensing in Fungi. Eukaryot Cell 5 613 619

18. ShankE

KolterR

2009 New developments in microbial interspecies signaling. Curr Opin Microbiol 12 1 10

19. HughesDT

SperandioV

2008 Inter-kingdom signalling: communication between bacteria and their hosts. Nat Rev Micro 6 111 120

20. HornbyJM

JensenEC

LisecAD

TastoJJ

JahnkeB

2001 Quorum Sensing in the Dimorphic Fungus Candida albicans Is Mediated by Farnesol. Appl Environ Microbiol 67 2982 2992

21. HoganDA

VikA

KolterR

2004 A Pseudomonas aeruginosa quorum-sensing molecule influences Candida albicans morphology. Mol Microbiol 54 1212 1223

22. Davis-HannaA

PiispanenAE

StatevaLI

HoganDA

2008 Farnesol and dodecanol effects on the Candida albicans Ras1-cAMP signalling pathway and the regulation of morphogenesis. Mol Microbiol 67 47 62

23. PalkovaZ

JanderovaB

GabrielJ

ZikanovaB

PospisekM

1997 Ammonia mediates communication between yeast colonies. Nature 390 532 536

24. BahnY-S

CoxGM

PerfectJR

HeitmanJ

2005 Carbonic Anhydrase and CO2 Sensing during Cryptococcus neoformans Growth, Differentiation, and Virulence. Curr Biol 15 2013 2020

25. Gewiss MogensenE

JanbonGuilhem

ChaloupkaJames

SteegbornClemens

FuMan Shun

2006 Cryptococcus neoformans Senses CO2 through the Carbonic Anhydrase Can2 and the Adenylyl Cyclase Cac1. Eukaryotic Cell 5 103 111

26. SharabiK

LecuonaE

HeleniusIT

BeitelG

SznajderJI

2009 Sensing, physiological effects and molecular response to elevated CO2 levels in eukaryotes. Journal of Cellular and Molecular Medicine 9999

27. ChristensenBE

FacerJF

1939 Simple wet combustion method for the determination of carbon, oxygen equivalence and empirical formula by iodic acid oxidation. J Am Chem Soc 61 3001 3005

28. ChenY

CannMJ

LitvinTN

IourgenkoV

SinclairML

2000 Soluble Adenylyl Cyclase as an Evolutionarily Conserved Bicarbonate Sensor. Science 289 625 628

29. CannMJ

HammerA

ZhouJ

KanacherT

2003 A Defined Subset of Adenylyl Cyclases Is Regulated by Bicarbonate Ion. J Biol Chem 278 35033 35038

30. SteegbornC

LitvinTN

LevinLR

BuckJ

WuH

2005 Bicarbonate activation of adenylyl cyclase via promotion of catalytic active site closure and metal recruitment. Nat Struct Mol Biol 12 32 37

31. GhoshS

NavarathnaDHMLP

RobertsDD

CooperJT

AtkinAL

2009 Arginine-Induced Germ Tube Formation in Candida albicans Is Essential for Escape from Murine Macrophage Line RAW 264.7. Infect Immun 77 1596 1605

32. BeldenWJ

LarrondoLF

FroehlichAC

ShiM

ChenC-H

2007 The band mutation in Neurospora crassa is a dominant allele of ras-1 implicating RAS signaling in circadian output. Genes & Dev 21 1494 1505

33. ParkS

LeeK

2004 Inverted race tube assay for circadian clock studies of the Neurospora accessions. Fungal Genet Newslett 51 12 14

34. HeleniusIT

KrupinskiT

TurnbullDW

GruenbaumY

SilvermanN

2009 Elevated CO2 suppresses specific Drosophila innate immune responses and resistance to bacterial infection. Proceedings of the National Academy of Sciences 106 18710 18715

35. De Smet

HildeR

BerstenAD

BarrHA

DoyleIR

2007 Hypercapnic acidosis modulates inflammation, lung mechanics, and edema in the isolated perfused lung. Journal of Critical Care 22 305 313

36. HalbertsmaFJJ

VanekerM

PickkersP

SnijdelaarDG

van EgmondJ

2008 Hypercapnic acidosis attenuates the pulmonary innate immune response in ventilated healthy mice. Critical Care Medicine 36 2403 2406

37. O'CroininDF

NicholAD

HopkinsN

BoylanJ

O'BrienS

2008 Sustained hypercapnic acidosis during pulmonary infection increases bacterial load and worsens lung injury. Critical Care Medicine 36 2128 2135

38. EllnerPD

StoesselCJ

DrakefordE

VasiF

1966 A new culture medium for clinical bacteriology. American Journal of Clinical Pathology 45 502 504

39. ThorpeTC

WilsonML

TurnerJE

DiGuiseppiJL

WillertM

1990 BacT/Alert: an automated colorimetric microbial detection system. J Clin Microbiol 28 1608 1612

40. SaliA

BlundellTL

1993 Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 234 779 815

41. WaltherA

WendlandJ

2003 An improved transformation protocol for the human fungal pathogen Candida albicans. Curr Genetics 42 339 343

42. MacCallumDM

CosteA

IscherF

JacobsenMD

OddsFC

2010 Genetic Dissection of Azole Resistance Mechanisms in Candida albicans and Their Validation in a Mouse Model of Disseminated Infection. Antimicrob Agents Chemother 54 1476 1483