Bactericidal Activity of Mammalian Cathelicidin-Derived Peptides

Sue M Travis; Norma N Anderson; William R Forsyth; Cesar Espiritu; Barbara D Conway; E. P Greenberg; Paul B McCray; Robert I Lehrer; Michael J Welsh; Brian F Tack

doi:10.1128/IAI.68.5.2748-2755.2000

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Bactericidal Activity of Mammalian Cathelicidin-Derived Peptides

Journal article

Open access

Peer reviewed

Bactericidal Activity of Mammalian Cathelicidin-Derived Peptides

Sue M Travis, Norma N Anderson, William R Forsyth, Cesar Espiritu, Barbara D Conway, E. P Greenberg, Paul B McCray, Robert I Lehrer, Michael J Welsh and Brian F Tack

Infection and immunity, Vol.68(5), pp.2748-2755

05/2000

DOI: 10.1128/IAI.68.5.2748-2755.2000

PMCID: PMC97484

PMID: 10768969

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Abstract

Endogenous antimicrobial peptides of the cathelicidin family contribute to innate immunity. The emergence of widespread antibiotic resistance in many commonly encountered bacteria requires the search for new bactericidal agents with therapeutic potential. Solid-phase synthesis was employed to prepare linear antimicrobial peptides found in cathelicidins of five mammals: human (FALL39/LL37), rabbit (CAP18), mouse (mCRAMP), rat (rCRAMP), and sheep (SMAP29 and SMAP34). These peptides were tested at ionic strengths of 25 and 175 mM against Pseudomonas aeruginosa , Escherichia coli , Staphylococcus aureus , and methicillin-resistant Staphylococcus aureus . Each peptide manifested activity against P. aeruginosa irrespective of the NaCl concentration. CAP18 and SMAP29 were the most effective peptides of the group against all test organisms under both low- and high-salt conditions. Select peptides of 15 to 21 residues, modeled on CAP18 (37 residues), retained activity against the gram-negative bacteria and methicillin-sensitive S. aureus , although the bactericidal activity was reduced compared to that of the parent peptide. In accordance with the behavior of the parent molecule, the truncated peptides adopted an α-helical structure in the presence of trifluoroethanol or lipopolysaccharide. The relationship between the bactericidal activity and several physiochemical properties of the cathelicidins was examined. The activities of the full-length peptides correlated positively with a predicted gradient of hydrophobicity along the peptide backbone and with net positive charge; they correlated inversely with relative abundance of anionic residues. The salt-resistant, antimicrobial properties of CAP18 and SMAP29 suggest that these peptides or congeneric structures have potential for the treatment of bacterial infections in normal and immunocompromised persons and individuals with cystic fibrosis.

Microbial Immunity and Vaccines

Details

Title: Subtitle: Bactericidal Activity of Mammalian Cathelicidin-Derived Peptides
Creators: Sue M Travis - Departments of Microbiology
Norma N Anderson - Departments of Microbiology
William R Forsyth - Departments of Microbiology
Cesar Espiritu - Departments of Microbiology
Barbara D Conway - Departments of Microbiology
E. P Greenberg - Departments of Microbiology
Paul B McCray - Departments of Microbiology
Robert I Lehrer - Departments of Microbiology
Michael J Welsh - Departments of Microbiology
Brian F Tack - Departments of Microbiology
Resource Type: Journal article
Publication Details: Infection and immunity, Vol.68(5), pp.2748-2755
DOI: 10.1128/IAI.68.5.2748-2755.2000
PMID: 10768969
PMCID: PMC97484
NLM abbreviation: Infect Immun
ISSN: 0019-9567
eISSN: 1098-5522
Publisher: American Society for Microbiology
Language: English
Date published: 05/2000
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Neurosurgery; Internal Medicine
Record Identifier: 9984020854102771

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