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Article

Improving the Efficacy of Antimicrobials against Biofilm-Embedded Bacteria Using Bovine Hyaluronidase Azoximer (Longidaza®)

1
Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia
2
Limnological Institute of the Siberian Branch of the Russian Academy of Sciences, 664000 Irkutsk, Russia
3
Biomedical Engineering Research Centre, St. Petersburg Electrotechnical University, 197022 St. Petersburg, Russia
4
NPO Petrovax Pharma LLC, 123112 Moscow, Russia
*
Author to whom correspondence should be addressed.
Academic Editors: Alan J. Hibbitts and Sofia A. Papadimitriou
Pharmaceutics 2021, 13(11), 1740; https://doi.org/10.3390/pharmaceutics13111740
Received: 24 September 2021 / Revised: 8 October 2021 / Accepted: 13 October 2021 / Published: 20 October 2021
While in a biofilm, bacteria are extremely resistant to both antimicrobials and the immune system, leading to the development of chronic infection. Here, we show that bovine hyaluronidase fused with a copolymer of 1,4-ethylenepiperazine N-oxide and (N-carboxymethyl) -1,4-ethylenepiperazinium bromide (Longidaza®) destroys both mono- and dual-species biofilms formed by various bacteria. After 4 h of treatment with 750 units of the enzyme, the residual biofilms of Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae preserved about 50–70% of their initial mass. Biomasses of dual-species biofilms formed by S. aureus and the four latter species were reduced 1.5-fold after 24 h treatment, while the significant destruction of S. aureus–P. aeruginosa and S. aureus–K. pneumoniae was also observed after 4 h of treatment with Longidaza®. Furthermore, when applied in combination, Longidaza® increased the efficacy of various antimicrobials against biofilm-embedded bacteria, although with various increase-factor values depending on both the bacterial species and antimicrobials chosen. Taken together, our data indicate that Longidaza® destroys the biofilm structure, facilitating the penetration of antimicrobials through the biofilm, and in this way improving their efficacy, lowering the required dose and thus also potentially reducing the associated side effects. View Full-Text
Keywords: bacterial biofilms; enzymatic destruction of the biofilm; bovine hyaluronidase azoximer (Longidaza) bacterial biofilms; enzymatic destruction of the biofilm; bovine hyaluronidase azoximer (Longidaza)
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MDPI and ACS Style

Trizna, E.; Baidamshina, D.; Gorshkova, A.; Drucker, V.; Bogachev, M.; Tikhonov, A.; Kayumov, A. Improving the Efficacy of Antimicrobials against Biofilm-Embedded Bacteria Using Bovine Hyaluronidase Azoximer (Longidaza®). Pharmaceutics 2021, 13, 1740. https://doi.org/10.3390/pharmaceutics13111740

AMA Style

Trizna E, Baidamshina D, Gorshkova A, Drucker V, Bogachev M, Tikhonov A, Kayumov A. Improving the Efficacy of Antimicrobials against Biofilm-Embedded Bacteria Using Bovine Hyaluronidase Azoximer (Longidaza®). Pharmaceutics. 2021; 13(11):1740. https://doi.org/10.3390/pharmaceutics13111740

Chicago/Turabian Style

Trizna, Elena, Diana Baidamshina, Anna Gorshkova, Valentin Drucker, Mikhail Bogachev, Anton Tikhonov, and Airat Kayumov. 2021. "Improving the Efficacy of Antimicrobials against Biofilm-Embedded Bacteria Using Bovine Hyaluronidase Azoximer (Longidaza®)" Pharmaceutics 13, no. 11: 1740. https://doi.org/10.3390/pharmaceutics13111740

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