Research

Monensin causes dose dependent inhibition of Mycobacterium avium subspecies paratuberculosis in radiometric culture

Robert J Greenstein¹ , Liya Su² , Robert H Whitlock³ and Sheldon T Brown²

¹  Laboratory of Molecular Surgical Research, VAMC Bronx, NY (112), 130 West Kingsbridge Road, Bronx, NY 10468, USA

²  VAMC Bronx NY, 130 West Kingsbridge Road, Bronx, NY 10468, USA

³  School of Veterinary Medicine, University of Pennsylvania, 382 West Street Road, Kennett Square, PA 19348, USA

author email corresponding author email

Gut Pathogens 2009, 1:4doi:10.1186/1757-4749-1-4

Published:	9 February 2009

Abstract

Background

Mycobacterium avium subspecies paratuberculosis (MAP) causes a chronic wasting diarrheal disease in ruminants called Johne's disease, that is evocative of human inflammatory bowel disease (IBD). Agents used to treat IBD, called "anti-inflammatories", immuno-modulators" and "immuno-suppressants" inhibit MAP growth in culture. We concluded that, unknowingly, the medical profession has been treating MAP since sulfasalazine's introduction in 1942. Monensin, called a "Growth Enhancer" in cattle, ameliorates Johne's disease without a documented mechanism of action. We hypothesized that Monensin would inhibit MAP in culture.

Methods

Using the radiometric ¹⁴CO₂ Bactec^® system, that expresses mycobacterial growth in arbitrary growth index (GI) units, we studied the effect of Monensin on the growth kinetic of MAP isolated from humans with IBD ("Dominic", "Ben" & UCF-4) and cattle with Johne's disease (303 & ATCC 19698.) Results are expressed as percent inhibition of cumulative GI (%–ΔcGI).

Results

The positive control Clofazimine inhibits every strain tested. The negative controls Cycloheximide & Phthalimide, have no inhibition on any MAP strain. Monensin has dose dependent inhibition on every MAP strain tested. The most susceptible human isolate was UCF-4 (73% – ΔcGI at 1 μg/ml) and bovine isolate was 303 (73% – ΔcGI at 4 μg/ml.) Monensin additionally inhibits M. avium ATCC 25291 (87% – ΔcGI at 64 μg/ml) & BCG (92% – ΔcGI at 16 μg/ml).

Discussion

We show that in radiometric culture the "Growth Enhancer" Monensin causes dose dependent inhibition of mycobacteria including MAP. We posit that the "Growth Enhancer" effect of Monensin may, at least in part, be due to inhibition of MAP in clinical or sub-clinical Johne's disease.