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

Greenstein RJ, Su L, Whitlock RH, Brown ST - Gut Pathog (2009)

Bottom Line: We concluded that, unknowingly, the medical profession has been treating MAP since sulfasalazine's introduction in 1942.Monensin has dose dependent inhibition on every MAP strain tested.The most susceptible human isolate was UCF-4 (73% - Delta cGI at 1 microg/ml) and bovine isolate was 303 (73% - Delta cGI at 4 microg/ml.) Monensin additionally inhibits M. avium ATCC 25291 (87% - Delta cGI at 64 microg/ml) & BCG (92% - Delta cGI at 16 microg/ml).

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Molecular Surgical Research, VAMC Bronx, NY (112), 130 West Kingsbridge Road, Bronx, NY 10468, USA. BGAxis@aol.com

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 (%-Delta cGI).

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% - Delta cGI at 1 microg/ml) and bovine isolate was 303 (73% - Delta cGI at 4 microg/ml.) Monensin additionally inhibits M. avium ATCC 25291 (87% - Delta cGI at 64 microg/ml) & BCG (92% - Delta cGI at 16 microg/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.

No MeSH data available.


Related in: MedlinePlus

Presents the dose dependent inhibition data for Monensin on isolates of MAP from cows with Johne's disease, ATCC 19698 and 303. Error bars are ± SD.
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Figure 2: Presents the dose dependent inhibition data for Monensin on isolates of MAP from cows with Johne's disease, ATCC 19698 and 303. Error bars are ± SD.

Mentions: For ease of comprehension, data are presented in two ways: For individual mycobacterial strains, data are presented as Figures using the cumulative Growth Index (cGI). For individual chemicals the same data, recalculated as %–ΔcGI [11,13], are presented as Tables. Figure 1 = MAP isolated from humans with Crohn's Disease. Figure 2 = Bovine Isolates of MAP from animals with Johne's disease. Figure 3 is M. avium subspecies avium. Figure 4 presents data for BCG. Table 1 is the positive antibiotic control Clofazimine (used in leprosy [40] and clinical trials of Crohn's disease [41,42].) The negative controls are the gluterimide antibiotics cycloheximide (Table 2) and phthalimide (Table 3.) The study results on Monensin are presented in Table 4.


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

Greenstein RJ, Su L, Whitlock RH, Brown ST - Gut Pathog (2009)

Presents the dose dependent inhibition data for Monensin on isolates of MAP from cows with Johne's disease, ATCC 19698 and 303. Error bars are ± SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2664324&req=5

Figure 2: Presents the dose dependent inhibition data for Monensin on isolates of MAP from cows with Johne's disease, ATCC 19698 and 303. Error bars are ± SD.
Mentions: For ease of comprehension, data are presented in two ways: For individual mycobacterial strains, data are presented as Figures using the cumulative Growth Index (cGI). For individual chemicals the same data, recalculated as %–ΔcGI [11,13], are presented as Tables. Figure 1 = MAP isolated from humans with Crohn's Disease. Figure 2 = Bovine Isolates of MAP from animals with Johne's disease. Figure 3 is M. avium subspecies avium. Figure 4 presents data for BCG. Table 1 is the positive antibiotic control Clofazimine (used in leprosy [40] and clinical trials of Crohn's disease [41,42].) The negative controls are the gluterimide antibiotics cycloheximide (Table 2) and phthalimide (Table 3.) The study results on Monensin are presented in Table 4.

Bottom Line: We concluded that, unknowingly, the medical profession has been treating MAP since sulfasalazine's introduction in 1942.Monensin has dose dependent inhibition on every MAP strain tested.The most susceptible human isolate was UCF-4 (73% - Delta cGI at 1 microg/ml) and bovine isolate was 303 (73% - Delta cGI at 4 microg/ml.) Monensin additionally inhibits M. avium ATCC 25291 (87% - Delta cGI at 64 microg/ml) & BCG (92% - Delta cGI at 16 microg/ml).

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Molecular Surgical Research, VAMC Bronx, NY (112), 130 West Kingsbridge Road, Bronx, NY 10468, USA. BGAxis@aol.com

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 (%-Delta cGI).

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% - Delta cGI at 1 microg/ml) and bovine isolate was 303 (73% - Delta cGI at 4 microg/ml.) Monensin additionally inhibits M. avium ATCC 25291 (87% - Delta cGI at 64 microg/ml) & BCG (92% - Delta cGI at 16 microg/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.

No MeSH data available.


Related in: MedlinePlus