Testing the efficacy and toxicity of adenylyl cyclase inhibitors against enteric pathogens using in vitro and in vivo models of infection

Scott T. Moen, Carla A. Blumentritt, Terry M. Slater, Shilpa D. Patel, Christopher B. Tutt, Maria E. Estrella-Jimenez, Jennifer Pawlik, Laurie Sower, Vsevolod Popov, Catherine H. Schein, Scott R. Gilbertson, Johnny Peterson, Alfredo Torres

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1740-1749
Number of pages10
JournalInfection and Immunity
Volume78
Issue number4
DOIs
StatePublished - Apr 2010

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Enterotoxigenic Escherichia coli
Cyclic AMP
Infection
Adenylyl Cyclases
Epithelial Cells
ADP Ribose Transferases
Bacteria
Bacterial Toxins
Poisons
Enterotoxins
Cultured Cells
Diarrhea
Hot Temperature
Adenylyl Cyclase Inhibitors
In Vitro Techniques

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Testing the efficacy and toxicity of adenylyl cyclase inhibitors against enteric pathogens using in vitro and in vivo models of infection. / Moen, Scott T.; Blumentritt, Carla A.; Slater, Terry M.; Patel, Shilpa D.; Tutt, Christopher B.; Estrella-Jimenez, Maria E.; Pawlik, Jennifer; Sower, Laurie; Popov, Vsevolod; Schein, Catherine H.; Gilbertson, Scott R.; Peterson, Johnny; Torres, Alfredo.

In: Infection and Immunity, Vol. 78, No. 4, 04.2010, p. 1740-1749.

Research output: Contribution to journalArticle

Moen, ST, Blumentritt, CA, Slater, TM, Patel, SD, Tutt, CB, Estrella-Jimenez, ME, Pawlik, J, Sower, L, Popov, V, Schein, CH, Gilbertson, SR, Peterson, J & Torres, A 2010, 'Testing the efficacy and toxicity of adenylyl cyclase inhibitors against enteric pathogens using in vitro and in vivo models of infection', Infection and Immunity, vol. 78, no. 4, pp. 1740-1749. https://doi.org/10.1128/IAI.01114-09
Moen, Scott T. ; Blumentritt, Carla A. ; Slater, Terry M. ; Patel, Shilpa D. ; Tutt, Christopher B. ; Estrella-Jimenez, Maria E. ; Pawlik, Jennifer ; Sower, Laurie ; Popov, Vsevolod ; Schein, Catherine H. ; Gilbertson, Scott R. ; Peterson, Johnny ; Torres, Alfredo. / Testing the efficacy and toxicity of adenylyl cyclase inhibitors against enteric pathogens using in vitro and in vivo models of infection. In: Infection and Immunity. 2010 ; Vol. 78, No. 4. pp. 1740-1749.
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