مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Antimicrobial Peptides as New Treatments for Biofilm-Associated Infections: A Meta-Analysis of Efficacy in Models of Klebsiella pneumoniae and Acinetobacter baumannii
Antimicrobial Peptides as New Treatments for Biofilm-Associated Infections: A Meta-Analysis of Efficacy in Models of Klebsiella pneumoniae and Acinetobacter baumannii
Zeinab Mohsenipour,1,*
1. Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Introduction: In the area of clinical microbiology, infections that affect biofilms pose challenges related to antibiotic therapy and host immune-directed defenses, because biofilms are largely resistant to both antibiotics and host immune mechanisms. Antimicrobial peptides (AMPs), small amphipathic molecules with broad-spectrum activity, which are suitable candidate for disrupting biofilms. This meta-analysis seeks to quantitatively evaluate the anti-biofilm effects of AMPs against Klebsiella pneumoniae and Acinetobacter baumannii by biofilm inhibition, metabolic inhibition, and reduction in bacterial viability.
Methods: To conduct our literature search, we searched PubMed, Scopus, and Web of Science, using the keywords antimicrobial peptides, biofilm, K. pneumoniae, and A. baumannii, between 2015 to 2025. Exclusion criteria included studies with no control groups or using non-standardized AMP concentrations.
Results: Collectively, in 42 studies (n = 1,248 experimental replicates), AMPs reduced biofilm mass significantly compared to untreated controls (SMD = -1.95; 94% CI: -2.21 to -1.37; p < 0.001). LL-37, DJK-5, and hbD3 were most potent, with biofilm mass reduced by >60% in K. pneumoniae and >50% in A. baumannii models. Bacterial metabolic activity in biofilm was suppressed (SMD = -1.64; 95% CI: -1.81 to -1.09; p < 0.001), with DJK-5 and Onc112 exhibiting potent suppression in resazurin assays. CLSM-based live/dead staining showed a notable rise in percentage of dead cells post-treatment (SMD = 1.65; 95% CI: 1.32 to 1.98; p < 0.001), primarily for older biofilms treated with DJK-5 labeled with rhodamine. Synthetic AMPs were comparatively more effective than natural peptides for biofilm inhibition (p = 0.03) and biofilms K. pneumoniae was more sensitive than A. baumannii (p = 0.05). Overall there is moderate heterogeneity among studies (I² = 46%), though differences in assay methods and concentration of peptide explains the variation.
Conclusion: This meta-analysis indicates that AMPs are indeed highly effective in inhibiting biofilm development for K. pneumoniae and A. baumannii, with a consistent reduction of biofilm density, viable bacteria, and biofilm metabolic activity. Rationally designed peptides such as, DJK-5 and Onc112 were shown to be more effective than natural AMPs, which suggests rational design of AMPs improves the ability to compromise or pass biofilm barriers. Overall, we conclude that AMPs represent an effective adjunct or alternative to traditional antibiotics, especially for biofilm related infections where resistance mechanisms are already deeply embedded within biofilms. However, variation in methods of biofilm assessment and peptide preparation necessitate standardized methodologies for biofilm assessment in animal models and further translational research.
Future endeavors should entail advancing AMP delivery vehicles (ex. hydrogels or nanoparticles), elucidating resistance mechanisms, and validating in clinical models of infection in tissue. Now more than ever with the growing urgency to treat infections caused by MDR biofilm, AMPs emerge as an attractive target in anti-infective strategies.