Are antimicrobial peptides ending the Antibiotic Crisis?

Antibiotic resistance is a major worldwide threat, rising to dangerous levels in which first-line antibiotics will no longer be effective. In this study researchers at Freie Universität Berlin, Germany described the use of antimicrobial peptides (AMPs) as an alternative approach against bacterial resistance. Using sub-lethal doses of AMPs, they demonstrated that bacteria develop both tolerance and persistence to the treatment by increasing the production of curli and colonic acid, which are extracellular matrix (ECM) components important for biofilm formation. The authors studied the emergence of priming and resistance to AMPs by priming Escherichia coli with sub-lethal doses of mellitin and pexiganan. They used EbbaBiolight 680 to label the extracellular matrix component curli and found increased curli production in bacteria primed with mellitin. Together with findings from transcriptomics and killing assays, the authors were able to conclude that priming with sublethal doses of AMPs, leads to an increase in tolerance and persistence, promoting bacteria survival compared to their native counterparts.
Altogether, the study shows that exposure to sub-lethal doses of AMPs correlates with an increase in tolerance and persistence by promoting biofilm formation, and hence, bacterial survival and colonisation. The results suggest that for a correct use of AMPs, a fast increase in their concentration should be provided to avoid bacterial priming, which will translate into resistance evolution. The findings shed light on how non-inherited resistance is acquired and open new paths to investigate measures to combat bacterial resistance.

Image: Graphical summary of the study. While high concentration of AMPs avoids bacterial survival, low concentration results in increased biofilm formation, tolerance and persistence, correlated with evolution to resistance.

Note: In the publication by Rodriguex-Rojas et al., the previous commercial name for EbbaBiolight is used. All claims made for ECtracer 680 in this publication can be applied to EbbaBiolight 680.

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