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Updated: Jul 7, 2026

Organotypic Tissue Model Systems for Investigating Host-Pathogen Interactions In Vitro
Published on: March 28, 2025
SMAP29 congeners demonstrate activity against oral bacteria and reduced toxicity against oral keratinocytes
P L Weistroffer1, S Joly, R Srikantha
1Department of Periodontics, College of Dentistry, University of Iowa, Iowa City, IA 52242, USA.
Introduction:
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.
Conclusion:
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.
Insights
Sheep cathelicidins SMAP29 and SMAP28 show potent antimicrobial activity against oral bacteria. Their congeners may offer a novel alternative for treating periodontal diseases with minimal toxicity.
Area of Science:
- Antimicrobial Peptides
- Oral Microbiology
- Biochemistry
Background:
- Cathelicidins are crucial antimicrobial peptides in host defense.
- SMAP29, a sheep cathelicidin, exhibits antimicrobial properties against oral pathogens.
- This study investigates SMAP29, SMAP28, and related congeners.
Purpose of the Study:
- To evaluate the antimicrobial efficacy of SMAP29, SMAP28, and congeners against oral bacteria.
- To assess the cytotoxicity of these peptides on keratinocytes.
Main Methods:
- Radial diffusion assay to determine antimicrobial activity against key oral bacteria.
- Lactate dehydrogenase release assay to measure keratinocyte cytotoxicity.
Main Results:
- SMAP28 demonstrated the highest antimicrobial potency, with activity strongly correlated with SMAP29.
- Congeners also showed antimicrobial effects, with varying efficacy against different bacterial strains.
- Cytotoxicity was dose- and length-dependent, with SMAP14A being the least toxic.
Conclusions:
- SMAP29 congeners exhibit significant antimicrobial activity against oral microorganisms.
- Minimal observed toxicity suggests potential as alternatives to traditional antibiotics for oral diseases.
- These findings support the development of cathelicidin-based therapies for periodontal conditions.

