| Testing the efficacy and toxicity of adenylyl cyclase inhibitors against enteric pathogens using in vitro and in vivo models of infection. | |
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MedLine Citation:
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PMID: 20123712 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Enterotoxigenic Escherichia coli (ETEC) produces the ADP-ribosyltransferase toxin known as heat-labile enterotoxin (LT). In addition to the toxic effect of LT resulting in increases of cyclic AMP (cAMP) and disturbance of cellular metabolic processes, this toxin promotes bacterial adherence to intestinal epithelial cells (A. M. Johnson, R. S. Kaushik, D. H. Francis, J. M. Fleckenstein, and P. R. Hardwidge, J. Bacteriol. 191:178-186, 2009). Therefore, we hypothesized that the identification of a compound that inhibits the activity of the toxin would have a suppressive effect on the ETEC colonization capabilities. Using in vivo and in vitro approaches, we present evidence demonstrating that a fluorenone-based compound, DC5, which inhibits the accumulation of cAMP in intoxicated cultured cells, significantly decreases the colonization abilities of adenylyl cyclase toxin-producing bacteria, such as ETEC. These findings established that DC5 is a potent inhibitor both of toxin-induced cAMP accumulation and of ETEC adherence to epithelial cells. Thus, DC5 may be a promising compound for treatment of diarrhea caused by ETEC and other adenylyl cyclase toxin-producing bacteria. |
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Authors:
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Scott T Moen; Carla A Blumentritt; Terry M Slater; Shilpa D Patel; Christopher B Tutt; Maria E Estrella-Jimenez; Jennifer Pawlik; Laurie Sower; Vsevolod L Popov; Catherine H Schein; Scott R Gilbertson; Johnny W Peterson; Alfredo G Torres |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-02-01 |
Journal Detail:
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Title: Infection and immunity Volume: 78 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-03-17 Completed Date: 2010-04-16 Revised Date: 2010-10-04 |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
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Languages: eng Pagination: 1740-9 Citation Subset: IM |
Affiliation:
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Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenylate Cyclase
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antagonists & inhibitors* Adhesins, Bacterial / metabolism* Animals Bacterial Adhesion / drug effects Bacterial Toxins / antagonists & inhibitors* Cell Line Colony Count, Microbial Enterotoxigenic Escherichia coli / pathogenicity* Enterotoxins / antagonists & inhibitors* Enzyme Inhibitors / administration & dosage*, pharmacology, toxicity Epithelial Cells / microbiology Escherichia coli Infections / prevention & control* Escherichia coli Proteins / antagonists & inhibitors* Female Fluorenes / administration & dosage, pharmacology, toxicity Humans Inhibitory Concentration 50 Intestine, Small / microbiology, pathology Macrophages / microbiology Mice |
| Chemical | |
Reg. No./Substance:
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0/Adhesins, Bacterial; 0/Bacterial Toxins; 0/Enterotoxins; 0/Enzyme Inhibitors; 0/Escherichia coli Proteins; 0/Fluorenes; 0/heat-labile enterotoxin, E coli; EC 4.6.1.1/Adenylate Cyclase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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