The occurrence of drug resistance is global healthcare concern, and although new drugs are constantly being sought, the pace of development is slow compared to the evolution and spread of multidrug resistant bacteria. The high persistence of bacteria in the form of both planktonic cells and biofilms on living tissues and medical surfaces calls for novel antibacterial strategies for the prevention and treatment of bacterial infections. In this study, enzymatic disruption of bacterial quorum sensing by acylase and ultrasound assisted nanospherization were innovatively combined to enhance the bactericidal efficacy of the conventional antibiotic gentamicin, lowering the drug dosage. The generated hybrid nanoantibacterials were stable, with zeta potential – 40 ± 0.23 mV and size of 200 ± 1nm. They possessed membrane disrupting capacity and killed the medically relevant Gram-negative Pseudomonas aeruginosa bacteria after 45 min. The synergistic combination demonstrated improved antibiofilm activity compared to the individual counterparts and reduced the resistant P. aeruginosa biofilm up to 6 logs. Moreover, the bactericidal efficaicy of the hybrids was not drastically affected in “protein corona” conditions, demonstrating their real application scenario. Further in situ ultrasound assisted synthesis and deposition of the acylase enzyme and gentamicin onto the surface of urinary catheters increased the life span of the medical devices and decreased the occurrence of bacterial biofilms. The obtained hybrid nanoantibacterials with complimentary modes of action were not found innocuous towards human fibroblasts (BJ-5ta cells) and as a such might be valuable alternative to control bacterial diseases at reduced antibiotic dosages.

Hybrid nanoantibacterials for controlling bacterial infections and spread of drug resistance

255th National Meeting (2018)

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