Abstract
Antimicrobial peptides (AMPs) are conserved evolutionary components of the innate immune system that are being tested as alternatives to antibiotics. Slow release of AMPs using biodegradable polymers can be advantageous in maintaining high peptide levels for topical treatment, especially in the oral environment in which dosage retention is challenged by drug dilution with saliva flow and by drug inactivation by salivary enzymatic activity. Enterococcus faecalis is a multidrug resistant nosocomial pathogen and a persistent pathogen in root canal infections. In this study, four ultra-short lipopeptides (C16-KGGK, C16-KLLK, C16-KAAK and C16-KKK) and an amphipathic α-helical antimicrobial peptide (Amp-1D) were tested against E. faecalis. The antibacterial effect was determined against planktonic bacteria and bacteria grown in biofilm. Of the five tested AMPs, C16-KGGK was the most effective. Next C16-KGGK was formulated with one of two polymers poly (lactic acid co castor oil) (DLLA) or ricinoleic acid-based poly (ester-anhydride) P(SA-RA). Peptide-synthetic polymer conjugates, also referred to as biohybrid mediums were tested for antibacterial activity against E. faecalis grown in suspension and in biofilms. The new formulations exhibited strong and improved anti- E. faecalis activity.
Highlights
The widespread use of antibiotics leads to the emergence of more resistant and virulent strains of microorganisms
Growth of E. faecalis was not inhibited by human beta-defensin 3 (hBD3) at concentrations of up to 20 mg/ml
At concentrations below 5 mg/ml the growth of E. faecalis was not inhibited by C16-KGGK but was accelerated
Summary
The widespread use of antibiotics leads to the emergence of more resistant and virulent strains of microorganisms. The development of new antimicrobial agents becomes paramount for novel treatment options [1]. Bacterial resistance to antibiotics becomes even more complicated when dealing with bacterial biofilms. Potent antimicrobial components against a wide range of pathogens can be found in the innate immune system of various organisms including humans. An example is host-defense cationic antimicrobial peptides (AMPs) which are conserved evolutionary components that possess the capacity to kill invading microbes [2]. It is generally accepted that AMP-mediated killing typically occurs through microbial membrane disruption resulting in irreparable damage
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