The human antimicrobial peptides LL-37 and lactoferricin significantly enhanced the effectiveness of three common antibiotics against antibiotic-tolerant oral biofilms, including hard-to-treat anaerobic bacteria.
All antibiotic-peptide combinations enhancedBoth LL-37 and lactoferricin boosted the effectiveness of amoxicillin, clindamycin, and metronidazole against antibiotic-tolerant oral biofilms
What the researchers found
LL-37 and lactoferricin enhanced the anti-biofilm effect of amoxicillin and clindamycin in facultative anaerobic biofilms (S. mutans, S. sanguinis, A. naeslundii). Metronidazole, which was ineffective alone against these biofilms, showed significant biofilm reduction when combined with either peptide.
Obligate anaerobic biofilms (V. parvula, P. micra, F. nucleatum) showed enhanced tolerance to amoxicillin and clindamycin, likely due to metabolic downshifts. However, combining these antibiotics with LL-37 or lactoferricin markedly enhanced biofilm reduction for all three antibiotics. The peptides also appeared to promote dispersion of mature biofilms, suggesting a mechanism for overcoming biofilm-mediated antibiotic tolerance.
Why it matters
Oral infections like periodontitis affect billions worldwide, and biofilm-forming bacteria are notoriously resistant to antibiotics. Rather than developing new antibiotics, this approach uses the body's own antimicrobial peptides to make existing antibiotics more effective. This 'combination therapy' strategy could address antibiotic tolerance without contributing to antibiotic resistance.
How the study worked
Researchers grew two types of polymicrobial biofilms in vitro: facultative anaerobic (representing caries-associated bacteria) and obligate anaerobic (representing periodontal disease-associated bacteria). They tested LL-37 and human lactoferricin alone and in combination with amoxicillin, clindamycin, and metronidazole, measuring biofilm reduction and bacterial viability.
What this study cannot tell us
This is an in vitro study using laboratory-grown biofilms, which may not fully replicate the complexity of oral biofilms in the human mouth. The biofilm models used only 3 bacterial species each, while real oral biofilms contain hundreds of species. Peptide stability in saliva and the oral environment was not assessed. No in vivo or clinical data were generated. Cost and delivery challenges of antimicrobial peptides in clinical dental practice were not addressed.
How to read the evidence
This is an in vitro laboratory study using model biofilms. While the experimental design is sound and tests clinically relevant antibiotics, the findings are early-stage and have not been validated in vivo or clinically.
When this study was published
Published in 2021, this study is relatively recent and contributes to the growing evidence base for antimicrobial peptides as adjuncts to conventional antibiotic therapy.
The bigger picture
Antimicrobial resistance is a global health crisis, and biofilm infections are among the hardest to treat. LL-37 and lactoferricin are natural components of human innate immunity, and leveraging them to enhance antibiotic efficacy represents a promising 'adjuvant' approach. This concept extends beyond dentistry to any biofilm-associated infection, including wound infections, device-related infections, and chronic lung infections.
Questions still open
- Can LL-37 and lactoferricin maintain their antibiotic-enhancing effects in the complex environment of the human mouth with saliva and hundreds of bacterial species?
- What delivery systems could effectively deliver these peptides to oral biofilms in clinical practice?
- Would this peptide-antibiotic combination approach work against biofilms in other clinical settings beyond dentistry?
Common questions
What are LL-37 and lactoferricin?
Why are biofilms so hard to treat with antibiotics?
Read the original research
Targeting antibiotic tolerance in anaerobic biofilms associated with oral diseases: Human antimicrobial peptides LL-37 and lactoferricin enhance the antibiotic efficacy of amoxicillin, clindamycin and metronidazole.
Anaerobe, 71, 102439
Citation
Wuersching, Sabina Noreen; Huth, Karin Christine; Hickel, Reinhard; Kollmuss, Maximilian. (2021). Targeting antibiotic tolerance in anaerobic biofilms associated with oral diseases: Human antimicrobial peptides LL-37 and lactoferricin enhance the antibiotic efficacy of amoxicillin, clindamycin and metronidazole.. Anaerobe, 71, 102439. https://doi.org/10.1016/j.anaerobe.2021.102439