Abstract
To improve the action of already in use antibiotics or new antimicrobial agents against different bacteria, the development of effective combinations of antimicrobial peptides (AMPs) with enzymes that can quench the quorum (QQ) sensing of bacterial cells was undertaken. Enzymes hydrolyzing N-acyl homoserine lactones (AHLs) and peptides that are signal molecules of Gram-negative and Gram-positive bacterial cells, respectively, were estimated as “partners” for antibiotics and antimicrobial peptides in newly designed antimicrobial–enzymatic combinations. The molecular docking of six antimicrobial agents to the surface of 10 different QQ enzyme molecules was simulated in silico. This made it possible to choose the best variants among the target combinations. Further, bacterial cellulose (BC) was applied as a carrier for uploading such combinations to generally compose prototypes of effective dressing materials with morphology, providing good absorbance. The in vitro analysis of antibacterial activity of prepared BC samples confirmed the significantly enhanced efficiency of the action of AMPs (including polymyxin B and colistin, which are antibiotics of last resort) in combination with AHL-hydrolyzing enzymes (penicillin acylase and His6-tagged organophosphorus hydrolase) against both Gram-negative and Gram-positive cells.
Highlights
Bacterial cellulose (BC) is already considered an excellent exudate-removing wound dressing material that can be functionalized with some additives or modifications to avoid infections and reduce local pain [1,2,3]
One of these approaches is the use of antimicrobial agents in combination with enzymes providing quenching of the quorum sensing (QS) mechanism possessed by both Gram-positive (G(+)) and Gram-negative (G(−)) bacteria, which results in antibiotic resistance of their populations [9]
The following enzymes with different acyl homoserine lactones (AHLs)-hydrolyzing activity were selected based on a review of the literature for this work: lactonase from Bacillus thuringiensis (AiiA, PDB 2btn), penicillin acylase from Pseudomonas aeruginosa (PvdQ, PDB 4m1j) and recombinant human paraoxonase-2 (PON2)
Summary
Bacterial cellulose (BC) is already considered an excellent exudate-removing wound dressing material that can be functionalized with some additives or modifications to avoid infections and reduce local pain [1,2,3]. The development of new dressing materials should be based on modern approaches to the problem of bacterial resistance. One of these approaches is the use of antimicrobial agents in combination with enzymes providing quenching of the quorum sensing (QS) mechanism possessed by both Gram-positive (G(+)) and Gram-negative (G(−)) bacteria, which results in antibiotic resistance of their populations [9]. The enzymatic hydrolysis of the signaling molecules of bacterial cells in combination with antimicrobial agents looks very attractive generally [12,13] and especially regarding dressing materials. Since we did not find related investigations that have been done previously, the design of BC samples containing combinations of different quorum-quenching (QQ) enzymes with antimicrobial agents became the main purpose of the work
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