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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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/11/1740 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:10:26Z |
| format | Article |
| id | doaj.art-e7b121de72664b9faabb29cfa34ea540 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T05:10:26Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-e7b121de72664b9faabb29cfa34ea5402023-11-23T00:56:52ZengMDPI AGPharmaceutics1999-49232021-10-011311174010.3390/pharmaceutics13111740Improving the Efficacy of Antimicrobials against Biofilm-Embedded Bacteria Using Bovine Hyaluronidase Azoximer (Longidaza<sup>®</sup>)Elena Trizna0Diana Baidamshina1Anna Gorshkova2Valentin Drucker3Mikhail Bogachev4Anton Tikhonov5Airat Kayumov6Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaLimnological Institute of the Siberian Branch of the Russian Academy of Sciences, 664000 Irkutsk, RussiaLimnological Institute of the Siberian Branch of the Russian Academy of Sciences, 664000 Irkutsk, RussiaBiomedical Engineering Research Centre, St. Petersburg Electrotechnical University, 197022 St. Petersburg, RussiaNPO Petrovax Pharma LLC, 123112 Moscow, RussiaInstitute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, RussiaWhile 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.https://www.mdpi.com/1999-4923/13/11/1740bacterial biofilmsenzymatic destruction of the biofilmbovine hyaluronidase azoximer (Longidaza) |
| spellingShingle | 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>) Pharmaceutics bacterial biofilms enzymatic destruction of the biofilm bovine hyaluronidase azoximer (Longidaza) |
| title | 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_short | 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 r sup |
| topic | bacterial biofilms enzymatic destruction of the biofilm bovine hyaluronidase azoximer (Longidaza) |
| url | https://www.mdpi.com/1999-4923/13/11/1740 |
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