Document Detail


Human salivary histatin 5 causes disordered volume regulation and cell cycle arrest in Candida albicans.
MedLine Citation:
PMID:  12183519     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human salivary histatin 5 (Hst 5) is a nonimmune salivary protein with antifungal activity against an important human pathogen, Candida albicans. The candidacidal activity of histatins appears to be a distinctive multistep mechanism involving depletion of the C. albicans intracellular ATP content as a result of nonlytic ATP efflux. Hst 5 caused a loss of cell viability concomitant with a decrease in cellular volume as determined both by a classical candidacidal assay with exogenous Hst 5 and by using a genetically engineered C. albicans strain expressing Hst 5. Preincubation of C. albicans cells with pharmacological inhibitors of anion transport provided complete or substantial protection from Hst 5-induced killing and volume reduction of cells. Moreover, intracellular expression of Hst 5 resulted in a reduction in the population mean cell volume that was accompanied by an increase in the percentage of unbudded cells and C. albicans cells in the G(1) phase. Following expression of Hst 5, the smallest cells sorted by fluorescence-activated cell sorting from the total population did not replicate and were exclusively in the G(1) phase. Cells with intracellularly expressed Hst 5 had greatly reduced G(1) cyclin transcript levels, indicating that they arrested in the G(1) phase before the onset of Start. Our data demonstrate that a key determinant in the mechanism of Hst 5 toxicity in C. albicans cells is the disruption of regulatory circuits for cell volume homeostasis that is closely coupled with loss of intracellular ATP. This novel process of fungicidal activity by a human salivary protein has highlighted potential interactions of Hst 5 with volume regulatory mechanisms and the process of yeast cell cycle control.
Authors:
Didi Baev; Xuewei S Li; Jin Dong; Peter Keng; Mira Edgerton
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Infection and immunity     Volume:  70     ISSN:  0019-9567     ISO Abbreviation:  Infect. Immun.     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-08-16     Completed Date:  2002-09-18     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4777-84     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
Adenosine Triphosphate / metabolism
Antifungal Agents / pharmacology*
Base Sequence
Candida albicans / cytology*,  drug effects*,  genetics,  metabolism
Cell Cycle / drug effects
Chloride Channels / antagonists & inhibitors
Cyclins / genetics
DNA, Fungal / genetics
G1 Phase / drug effects
Histatins
Humans
Potassium Channel Blockers
RNA, Fungal / genetics,  metabolism
RNA, Messenger / genetics,  metabolism
Recombinant Proteins / genetics,  pharmacology
Salivary Proteins and Peptides / genetics,  pharmacology*
Grant Support
ID/Acronym/Agency:
DE00406/DE/NIDCR NIH HHS; DE10641/DE/NIDCR NIH HHS; R01 DE010641/DE/NIDCR NIH HHS; R01 DE010641-09/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
0/Antifungal Agents; 0/Chloride Channels; 0/Cyclins; 0/DNA, Fungal; 0/HTN3 protein, human; 0/Histatins; 0/Potassium Channel Blockers; 0/RNA, Fungal; 0/RNA, Messenger; 0/Recombinant Proteins; 0/Salivary Proteins and Peptides; 8L70Q75FXE/Adenosine Triphosphate; Q1O6DSW23R/4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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