Antifungal Properties and Target Evaluation of Three Putative Bacterial Histidine Kinase Inhibitors

Robert J Deschenes; Hong Lin; Addison D Ault; Jan S Fassler

doi:10.1128/AAC.43.7.1700

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Antifungal Properties and Target Evaluation of Three Putative Bacterial Histidine Kinase Inhibitors

Journal article

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Antifungal Properties and Target Evaluation of Three Putative Bacterial Histidine Kinase Inhibitors

Robert J Deschenes, Hong Lin, Addison D Ault and Jan S Fassler

Antimicrobial agents and chemotherapy, Vol.43(7), pp.1700-1703

07/01/1999

DOI: 10.1128/AAC.43.7.1700

PMCID: PMC89346

PMID: 10390225

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Abstract

Histidine protein kinases have been explored as potential antibacterial drug targets. The recent identification of two-component histidine kinases in fungi has led us to investigate the antifungal properties of three bacterial histidine kinase inhibitors (RWJ-49815, RWJ-49968, and RWJ-61907). All three compounds were found to inhibit growth of the Saccharomyces cerevisiae and Candida albicans strains, with MICs ranging from 1 to 20 μg/ml. However, deletion of SLN1, the only histidine kinase inS. cerevisiae, did not alter drug efficacy. In vitro kinase assays were performed by using the Sln1 histidine kinase purified from bacteria as a fusion protein to glutathione S-transferase. RWJ-49815 and RWJ-49968 inhibited kinase a 50% inhibitory concentration of 10 μM, whereas RWJ-61907 failed to inhibit at concentrations up to 100 μM. Based on these results, we conclude that these compounds have antifungal properties; however, their mode of action appears to be independent of histidine kinase inhibition.

Antifungal Agents

Enzyme Inhibitors

Guanidines

Mechanisms of Action: Physiological Effects

Protein Kinase Inhibitors

Protein Kinases

Trityl Compounds

Details

Title: Subtitle: Antifungal Properties and Target Evaluation of Three Putative Bacterial Histidine Kinase Inhibitors
Creators: Robert J Deschenes - Corresponding author. Mailing address: Department of Biochemistry, University of Iowa, Iowa City, IA 52242. Phone: 335-7884. Fax: 335-9570. E-mail:robert-deschenes@uiowa.edu
Hong Lin
Addison D Ault
Jan S Fassler
Resource Type: Journal article
Publication Details: Antimicrobial agents and chemotherapy, Vol.43(7), pp.1700-1703
Publisher: American Society for Microbiology
DOI: 10.1128/AAC.43.7.1700
PMID: 10390225
PMCID: PMC89346
ISSN: 0066-4804
eISSN: 1098-6596
Language: English
Date published: 07/01/1999
Academic Unit: Biology
Record Identifier: 9984217526702771

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