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Title: THE OVINE CATHELICIDIN SMAP29 KILLS OVINE RESPIRATORY PATHOGENS IN VITRO AND IN AN OVINE MODEL OF PULMONARY INFECTION

Author
item Brogden, Kim
item KALFA, VASIF
item ACKERMANN, MARK
item MCCRAY, JR., PAUL
item TACK, BRIAN

Submitted to: Antimicrobial Agents and Chemotherapy
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/6/2000
Publication Date: N/A
Citation: N/A

Interpretive Summary: Respiratory tract diseases are a leading cause of loss from disease in the cattle, sheep, and goat industries. Annual loss in the United States is estimated to exceed one billion dollars. Losses are from mortality, reduced feed efficiency, and slaughter condemnations, as well as prevention and treatment measures. Currently, scientists and veterinarians are looking at novel ways to prevent or treat the disease. As part of our ongoing studies, we assessed the antimicrobial activity of cathelicidins against a panel of sheep respiratory pathogens. Cathelicidins are antimicrobial peptides identified in rodents (mouse CRAMP and rat CRAMP), pigs, cows (BMAP27 and 28), sheep (SMAP29 and 34), rabbits (CAP18), and humans (LL37-h/CAP18). All organisms, except C. pseudotuberculosis, were susceptible to SMAP29 and CAP18. Mouse CRAMP, rat CRAMP, SMAP34, FALL39, and FF21 were less effective. The highly active nature of SMAP29 suggested dit might be effective in treating bacterial respiratory infections. To test this, we established a model of acute pneumonia in lambs. In infected lambs, a single bronchial instillation of SMAP29 reduced the concentration of bacteria in lung fluid and tissues. On the basis of our findings, it appears that SMAP29 may have applications in the treatment or prevention of respiratory infections. This would be an important factor in preventing or treating shipping fever of cattle. Corollary benefits include an increase in the profitability and international competitiveness of the U. S. cattle industry, a stronger rural economy, and a continued supply of inexpensive, wholesome beef and beef products for the American consumer.

Technical Abstract: Cathelicidins are antimicrobial peptides with broad-spectrum antibacterial activity. Although they have been shown to Pseudomonas aeruginosa, their activities against other pathogens have not been systemically investigated nor has their effectiveness in treating respiratory infections. Thus, we tested the susceptibility of a panel of ovine respiratory pathogens to synthesized natural cathelicidins. A dilution susceptibility test was use to obtain a minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). All organisms, except C. pseudotuberculosis, were susceptible to SMAP29 (MIC range 0.6 to 2.5 ug/ml) and CAP18 (MIC range 1.3 - 10.0 ug/ml). Mouse CRAMP, rat CRAMP, SMAP34, FALL39, and FF21 were less effective with MICs generally higher than that of SMAP29 and CAP18 for each organism. Anti-microbial activity of CAP18 congeners were also examined and the susceptibility of organisms varied greatly depending upon the peptide composition. Most Gram-negative bacteria were susceptible to CAP1831, CAP1828, CAP1822, and CAP1821a, and resistant to CAP1818, CAP1815a, and CAP1815b. Corynebacterium pseudotuberculosis and S. aureus were resistant (>/-20.0 ug/ml). The low MIC of SMAP29 in vitro suggested it might be effective in treating bacterial respiratory infections in vivo. To test this, we established a model of acute pneumonia in lambs using the ovine respiratory pathogen M. haemolytica. In infected lambs, a single bronchial instillation of 0.5 mg SMAP29 reduced the concentration of bacteria in both the BAL fluid and consolidated pulmonary tissues. In conclusion, the in vitro and in vivo effectiveness of SMAP29 suggests it may have applications in the treatment or prevention of pulmonary infections.