PMID- 19429755
OWN - NLM
STAT- MEDLINE
DCOM- 20090630
LR  - 20211020
IS  - 0022-2615 (Print)
IS  - 1473-5644 (Electronic)
IS  - 0022-2615 (Linking)
VI  - 58
IP  - Pt 6
DP  - 2009 Jun
TI  - Inhibitors of cellular signalling are cytotoxic or block the budded-to-hyphal 
      transition in the pathogenic yeast Candida albicans.
PG  - 779-790
LID - 10.1099/jmm.0.006841-0 [doi]
AB  - The pathogenic yeast Candida albicans can grow in multiple morphological states 
      including budded, pseudohyphal and true hyphal forms. The ability to interconvert 
      between budded and hyphal forms, herein termed the budded-to-hyphal transition 
      (BHT), is important for C. albicans virulence, and is regulated by multiple 
      environmental and cellular signals. To identify small-molecule inhibitors of 
      known cellular processes that can also block the BHT, a microplate-based 
      morphological assay was used to screen the BIOMOL-Institute of Chemistry and Cell 
      Biology (ICCB) Known Bioactives collection from the ICCB-Longwood Screening 
      Facility (Harvard Medical School, Boston, MA, USA). Of 480 molecules tested, 53 
      were cytotoxic to C. albicans and 16 were able to block the BHT without 
      inhibiting budded growth. These 16 BHT inhibitors affected protein kinases, 
      protein phosphatases, Ras signalling pathways, G protein-coupled receptors, 
      calcium homeostasis, nitric oxide and guanylate cyclase signalling, and apoptosis 
      in mammalian cells. Several of these molecules were also able to inhibit 
      filamentous growth in other Candida species, as well as the pathogenic 
      filamentous fungus Aspergillus fumigatus, suggesting a broad fungal host range 
      for these inhibitory molecules. Results from secondary assays, including 
      hyphal-specific transcription and septin localization analysis, were consistent 
      with the inhibitors affecting known BHT signalling pathways in C. albicans. 
      Therefore, these molecules will not only be invaluable in deciphering the 
      signalling pathways regulating the BHT, but also may serve as starting points for 
      potential new antifungal therapeutics.
FAU - Toenjes, Kurt A
AU  - Toenjes KA
AD  - Department of Biological and Physical Sciences, Montana State University 
      Billings, Billings, MT 59101, USA.
AD  - Markey Center for Molecular Genetics, Department of Microbiology and Molecular 
      Genetics, University of Vermont, Burlington, VT 05405, USA.
FAU - Stark, Benjamin C
AU  - Stark BC
AD  - Markey Center for Molecular Genetics, Department of Microbiology and Molecular 
      Genetics, University of Vermont, Burlington, VT 05405, USA.
FAU - Brooks, Krista M
AU  - Brooks KM
AD  - Markey Center for Molecular Genetics, Department of Microbiology and Molecular 
      Genetics, University of Vermont, Burlington, VT 05405, USA.
FAU - Johnson, Douglas I
AU  - Johnson DI
AD  - Markey Center for Molecular Genetics, Department of Microbiology and Molecular 
      Genetics, University of Vermont, Burlington, VT 05405, USA.
LA  - eng
GR  - P20 GM103474/GM/NIGMS NIH HHS/United States
GR  - P20 RR016455/RR/NCRR NIH HHS/United States
GR  - P20 RR016455-08/RR/NCRR NIH HHS/United States
GR  - P20 RR16455/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - England
TA  - J Med Microbiol
JT  - Journal of medical microbiology
JID - 0224131
RN  - 0 (Antifungal Agents)
RN  - 0 (Culture Media)
SB  - IM
MH  - Antifungal Agents/chemistry/*pharmacology
MH  - Candida albicans/drug effects/*growth & development/pathogenicity
MH  - Culture Media
MH  - Gene Expression Regulation, Fungal
MH  - Humans
MH  - Hyphae/drug effects/*growth & development/pathogenicity
MH  - Microbial Sensitivity Tests/methods
MH  - Morphogenesis/drug effects
MH  - Signal Transduction/*drug effects
MH  - Virulence
PMC - PMC2742683
MID - NIHMS113395
EDAT- 2009/05/12 09:00
MHDA- 2009/07/01 09:00
PMCR- 2010/06/01
CRDT- 2009/05/12 09:00
PHST- 2009/05/12 09:00 [entrez]
PHST- 2009/05/12 09:00 [pubmed]
PHST- 2009/07/01 09:00 [medline]
PHST- 2010/06/01 00:00 [pmc-release]
AID - 779 [pii]
AID - 10.1099/jmm.0.006841-0 [doi]
PST - ppublish
SO  - J Med Microbiol. 2009 Jun;58(Pt 6):779-790. doi: 10.1099/jmm.0.006841-0.