Document Detail


Testing the efficacy and toxicity of adenylyl cyclase inhibitors against enteric pathogens using in vitro and in vivo models of infection.
MedLine Citation:
PMID:  20123712     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-01
Journal Detail:
Title:  Infection and immunity     Volume:  78     ISSN:  1098-5522     ISO Abbreviation:  Infect. Immun.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-17     Completed Date:  2010-04-16     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1740-9     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adenylate Cyclase / 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:
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
Comments/Corrections

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


Previous Document:  CD1d-dependent B-cell help by NK-like T cells leads to enhanced and sustained production of Bacillus...
Next Document:  Critical role of dispensable genes in Mycoplasma agalactiae interaction with mammalian cells.