SMAP29 congeners demonstrate activity against oral bacteria and reduced toxicity against oral keratinocytes.
BACKGROUND
Cathelicidins are antimicrobial peptides found in epithelial and mucosal tissues as well as the secondary granules of neutrophils. SMAP29, a sheep cathelicidin, has differential antimicrobial properties against various pathogens, including periodontal organisms. The purpose of this study was to evaluate the antimicrobial properties and cytotoxicity of SMAP29, SMAP28, and three congeners (SMAP18A, SMAP18D, and SMAP14A).


METHODS
The peptides at concentrations ranging from 0.25 to 250 microg/ml were tested for their activity against multiple strains of Streptococcus mutans, Streptococcus sanguis, Actinomyces israelii, Actinomyces naeslundii, Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Peptostreptococcus micros, and Porphyromonas gingivalis using a radial diffusion assay. Cytotoxicity of keratinocytes was evaluated by measuring lactate dehydrogenase release after incubation with the individual peptides.


RESULTS
SMAP28, thought to be the biologically active peptide, was the most potent antimicrobial (range of minimum inhibitory concentrations 0.06-7.03 microg/ml, P < 0.05); however, the activity of SMAP28 and SMAP29 was strongly associated (r = 0.933). The congeners also demonstrated antimicrobial activity against the bacteria tested (range of minimum inhibitory concnetrations 0.21-79 microg/ml). Overall, F. nucleatum was the most susceptible organism, while P. gingivalis was the least susceptible. Keratinocyte cytotoxicity was dependent on peptide length and dose. SMAP28 was the most cytotoxic, while SMAP14A was the least cytotoxic.


CONCLUSIONS
The antimicrobial activities against oral microorganisms and the minimal toxicity seen in this study suggest that the congeners of SMAP29 may serve as an alternative to traditional antibiotics in the prevention and treatment of periodontal and other oral diseases.
Weistroffer
P L
PL
Department of Periodontics, College of Dentistry, University of Iowa, Iowa City, IA 52242, USA.
Joly
S
S
Srikantha
R
R
Tack
B F
BF
Brogden
K A
KA
Guthmiller
J M
JM
D000190:Actinomyces / Q000187:drug effects; D016976:Aggregatibacter actinomycetemcomitans / Q000187:drug effects; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology* / Q000633:toxicity; D001421:Bacteria, Anaerobic / Q000187:drug effects*; D001798:Blood Proteins / Q000494:pharmacology* / Q000633:toxicity; D054804:Cathelicidins / Q000494:pharmacology* / Q000633:toxicity; D016967:Fusobacterium nucleatum / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010462:Peptostreptococcus / Q000187:drug effects; D016966:Porphyromonas gingivalis / Q000187:drug effects; D034561:Sheep, Domestic; D013291:Streptococcus / Q000187:drug effects
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D054804:Cathelicidins; C403305:SMAP29 protein, Ovis aries; C440189:ovispirin