Differential Antimicrobial Activity of Two LL37 Derivatives Against Periodontal Bacteria, Including Enhanced Efficacy Against P. gingivalis in the Presence of Cigarette Smoke

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Introduction: Periodontitis is a plaque-induced condition that causes irreparable damage to the supporting tissues of the teeth, and tobacco smoking is a recognized exacerbating and risk factor. Antibiotic-resistant bacteria are a consequence of antibiotic overuse. Antimicrobial peptides (AMPs) are innate immune system molecules that show promise in combating antibiotic resistance. Methods: The current work investigated the efficiency of two synthetic derivatives of AMP human cathelicidin LL37, FK13a1-NH2 and KR12-NH2, in inhibiting target periodontal bacteria such as Fusobacterium nucleatum, Porphyromonas gingivalis, and Streptococcus oralis, in the presence of cigarette smoke extract (CSE). The amount of cigarette smoke extracted from one cigarette was considered the initial CSE maximum concentration (100%). Among the techniques used were microdilution testing, checkerboard experiments, and confocal imaging. Results: The results of the investigation showed that the two synthesized AMPs effectively inhibited the growth of P. gingivalis and F. nucleatum in the planktonic phase. Combining 500 µg/ml of KR12-NH2 with 50% CSE resulted in 98% P. gingivalis growth inhibition. Both peptides also significantly reduced the thickness of single-species biofilms; however, their impacts on complex, multi-species biofilms were less noticeable. Conclusion: Peptides applied in the presence of CSE were effective against P. gingivalis, a major periodontal pathogen. Therefore, they may be a promising alternative to standard antibiotics against periodontal bacteria regardless of smoking status, warranting further investigation.

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