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United States Department of Agriculture

Agricultural Research Service

Title: CONGENERS OF SMAP29 KILL OVINE PATHOGENS AND INDUCE UTRASTRUCTURAL DAMAGE IN BACTERIAL CELLS

Authors
item Kalfa, V - UNIV. OF CA., LOS ANGELES
item Jia, H - UNIV. OF IOWA, IOWA CITY
item Kunkle, Robert
item Mccray, Jr, Paul - UNIV. OF IOWA, IOWA CITY
item Tack, Brian - UNIV. OF IOWA, IOWA CITY
item Brogden, Kim -

Submitted to: Antimicrobial Agents and Chemotherapy
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 8, 2001
Publication Date: N/A

Interpretive Summary: Respiratory tract diseases are a leading cause of loss from disease in the cattle, sheep, and goat industries. Annual losses in the United States are` estimated to exceed one billion dollars 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 systematically altered the size and amino acid composition of SMAP29 to create a family of 23 related peptides and determined their minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for 9 ovine pathogens and Aspergillus fumigatus in a broth microdilution susceptibility test. SMAP28, SMAP29, and a derivative of SMAP29 called ovispirin (OV) were all effective against Gram-negative bacteria (MIC range 0.1 to 10.0 ug/ml), Gram-positive bacteria (MIC range 0.8 to >20.0 ug/ml), and A. fumigatus (MIC 2.5 ug/ml). Congeners of SMAP2 were not as active, and MICs were generally higher (MIC range 0.3 to > 20.0 ug/ml). Congeners of OV (>16 residues) were more active than congeners (<16 residues). However, substituting residues in the peptide or adding an N-terminus amine improved antimicrobial activity of the latter. Corollary benefits of this work 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: Sheep myeloid antimicrobial peptide (SMAP) 29 is a cathelicidin with broad- spectrum antimicrobial activity. We systematically altered the size and amino acid composition of SMAP29 to create a family of 23 related peptides and determined their minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for 9 ovine pathogens and Aspergillus fumigatus in a broth microdilution susceptibility test. SMAP28, SMAP29, and a derivative of SMAP29 called ovispirin (OV) were all effective against Gram-negative bacteria (MIC range 0.1 to 10.0 ug/ml), Gram-positive bacteria (MIC range 0.8 to >20.0 ug/ml), and A. fumigatus (MIC 2.5 ug/ml). Congeners of SMAP29 were not as active and MICs were generally higher (MIC range 0.3 to > 20.0 ug/ml). Congeners of OV (>16 residues) were more active than congeners (<16 residues). However, substituting residues in the peptide or adding an N-terminus amine improved antimicrobial activity of the latter. With immunoelectron microscopy using antiserum against SMAP29 and protein G-colloidal gold, SMAP29 was detected on bacterial membranes of P. aeruginosa PAO1 and later within the bacterial cytoplasm.

Last Modified: 9/1/2014
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