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

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...

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Autores principales: Elena Trizna, Diana Baidamshina, Anna Gorshkova, Valentin Drucker, Mikhail Bogachev, Anton Tikhonov, Airat Kayumov
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:e7b121de72664b9faabb29cfa34ea5402021-11-25T18:40:17ZImproving the Efficacy of Antimicrobials against Biofilm-Embedded Bacteria Using Bovine Hyaluronidase Azoximer (Longidaza<sup>®</sup>)10.3390/pharmaceutics131117401999-4923https://doaj.org/article/e7b121de72664b9faabb29cfa34ea5402021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1740https://doaj.org/toc/1999-4923While 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<sup>®</sup>) 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 <i>Staphylococcus aureus</i>, <i>Enterococcus faecalis</i>, <i>Escherichia coli</i>, <i>Pseudomonas aeruginosa</i> and <i>Klebsiella pneumoniae</i> preserved about 50–70% of their initial mass. Biomasses of dual-species biofilms formed by <i>S. aureus</i> and the four latter species were reduced 1.5-fold after 24 h treatment, while the significant destruction of <i>S. aureus–P. aeruginosa</i> and <i>S. aureus–K. pneumoniae</i> was also observed after 4 h of treatment with Longidaza<sup>®</sup>. Furthermore, when applied in combination, Longidaza<sup>®</sup> 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<sup>®</sup> 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.Elena TriznaDiana BaidamshinaAnna GorshkovaValentin DruckerMikhail BogachevAnton TikhonovAirat KayumovMDPI AGarticlebacterial biofilmsenzymatic destruction of the biofilmbovine hyaluronidase azoximer (Longidaza)Pharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1740, p 1740 (2021)
institution DOAJ
collection DOAJ
language EN
topic bacterial biofilms
enzymatic destruction of the biofilm
bovine hyaluronidase azoximer (Longidaza)
Pharmacy and materia medica
RS1-441
spellingShingle bacterial biofilms
enzymatic destruction of the biofilm
bovine hyaluronidase azoximer (Longidaza)
Pharmacy and materia medica
RS1-441
Elena Trizna
Diana Baidamshina
Anna Gorshkova
Valentin Drucker
Mikhail Bogachev
Anton Tikhonov
Airat Kayumov
Improving the Efficacy of Antimicrobials against Biofilm-Embedded Bacteria Using Bovine Hyaluronidase Azoximer (Longidaza<sup>®</sup>)
description 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<sup>®</sup>) 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 <i>Staphylococcus aureus</i>, <i>Enterococcus faecalis</i>, <i>Escherichia coli</i>, <i>Pseudomonas aeruginosa</i> and <i>Klebsiella pneumoniae</i> preserved about 50–70% of their initial mass. Biomasses of dual-species biofilms formed by <i>S. aureus</i> and the four latter species were reduced 1.5-fold after 24 h treatment, while the significant destruction of <i>S. aureus–P. aeruginosa</i> and <i>S. aureus–K. pneumoniae</i> was also observed after 4 h of treatment with Longidaza<sup>®</sup>. Furthermore, when applied in combination, Longidaza<sup>®</sup> 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<sup>®</sup> 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.
format article
author Elena Trizna
Diana Baidamshina
Anna Gorshkova
Valentin Drucker
Mikhail Bogachev
Anton Tikhonov
Airat Kayumov
author_facet Elena Trizna
Diana Baidamshina
Anna Gorshkova
Valentin Drucker
Mikhail Bogachev
Anton Tikhonov
Airat Kayumov
author_sort Elena Trizna
title Improving the Efficacy of Antimicrobials against Biofilm-Embedded Bacteria Using Bovine Hyaluronidase Azoximer (Longidaza<sup>®</sup>)
title_short Improving the Efficacy of Antimicrobials against Biofilm-Embedded Bacteria Using Bovine Hyaluronidase Azoximer (Longidaza<sup>®</sup>)
title_full Improving the Efficacy of Antimicrobials against Biofilm-Embedded Bacteria Using Bovine Hyaluronidase Azoximer (Longidaza<sup>®</sup>)
title_fullStr Improving the Efficacy of Antimicrobials against Biofilm-Embedded Bacteria Using Bovine Hyaluronidase Azoximer (Longidaza<sup>®</sup>)
title_full_unstemmed Improving the Efficacy of Antimicrobials against Biofilm-Embedded Bacteria Using Bovine Hyaluronidase Azoximer (Longidaza<sup>®</sup>)
title_sort improving the efficacy of antimicrobials against biofilm-embedded bacteria using bovine hyaluronidase azoximer (longidaza<sup>®</sup>)
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/e7b121de72664b9faabb29cfa34ea540
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