Gram Negative Biofilms: Structural and Functional Responses to Destruction by Antibiotic-Loaded Mixed Polymeric Micelles
Biofilms are a well-known multifactorial virulence factor with a pivotal role in chronic bacterial infections. Their pathogenicity is determined by the combination of strain-specific mechanisms of virulence and the biofilm extracellular matrix (ECM) protecting the bacteria from the host immune defen...
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2024-12-01
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| author | Tsvetozara Damyanova Rumena Stancheva Milena N. Leseva Petya A. Dimitrova Tsvetelina Paunova-Krasteva Dayana Borisova Katya Kamenova Petar D. Petrov Ralitsa Veleva Ivelina Zhivkova Tanya Topouzova-Hristova Emi Haladjova Stoyanka Stoitsova |
| author_facet | Tsvetozara Damyanova Rumena Stancheva Milena N. Leseva Petya A. Dimitrova Tsvetelina Paunova-Krasteva Dayana Borisova Katya Kamenova Petar D. Petrov Ralitsa Veleva Ivelina Zhivkova Tanya Topouzova-Hristova Emi Haladjova Stoyanka Stoitsova |
| author_sort | Tsvetozara Damyanova |
| collection | DOAJ |
| description | Biofilms are a well-known multifactorial virulence factor with a pivotal role in chronic bacterial infections. Their pathogenicity is determined by the combination of strain-specific mechanisms of virulence and the biofilm extracellular matrix (ECM) protecting the bacteria from the host immune defense and the action of antibacterials. The successful antibiofilm agents should combine antibacterial activity and good biocompatibility with the capacity to penetrate through the ECM. The objective of the study is the elaboration of biofilm-ECM-destructive drug delivery systems: mixed polymeric micelles (MPMs) based on a cationic poly(2-(dimethylamino)ethyl methacrylate)-b-poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA<sub>35</sub>-b-PCL<sub>70</sub>-b-PDMAEMA<sub>35</sub>) and a non-ionic poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO<sub>100</sub>-b-PPO<sub>65</sub>-b-PEO<sub>100</sub>) triblock copolymers, loaded with ciprofloxacin or azithromycin. The MPMs were applied on 24 h pre-formed biofilms of <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i> (laboratory strains and clinical isolates). The results showed that the MPMs were able to destruct the biofilms, and the viability experiments supported drug delivery. The biofilm response to the MPMs loaded with the two antibiotics revealed two distinct patterns of action. These were registered on the level of both bacterial cell-structural alterations (demonstrated by scanning electron microscopy) and the interaction with host tissues (ex vivo biofilm infection model on skin samples with tests on nitric oxide and interleukin (IL)-17A production). |
| format | Article |
| id | doaj-art-15474e5c3000473889824f87ef8aa4e2 |
| institution | DOAJ |
| issn | 2076-2607 |
| language | English |
| publishDate | 2024-12-01 |
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| series | Microorganisms |
| spelling | doaj-art-15474e5c3000473889824f87ef8aa4e22025-08-20T02:50:41ZengMDPI AGMicroorganisms2076-26072024-12-011212267010.3390/microorganisms12122670Gram Negative Biofilms: Structural and Functional Responses to Destruction by Antibiotic-Loaded Mixed Polymeric MicellesTsvetozara Damyanova0Rumena Stancheva1Milena N. Leseva2Petya A. Dimitrova3Tsvetelina Paunova-Krasteva4Dayana Borisova5Katya Kamenova6Petar D. Petrov7Ralitsa Veleva8Ivelina Zhivkova9Tanya Topouzova-Hristova10Emi Haladjova11Stoyanka Stoitsova12Department of Microbiology, Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Akad. G. Bonchev Street, bl. 26, 1113 Sofia, BulgariaInstitute of Polymers, Bulgarian Academy of Sciences, Akad. G. Bonchev Street, bl. 103-A, 1113 Sofia, BulgariaDepartment of Immunology, Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Akad. G. Bonchev Street, bl. 26, 1113 Sofia, BulgariaDepartment of Immunology, Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Akad. G. Bonchev Street, bl. 26, 1113 Sofia, BulgariaDepartment of Microbiology, Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Akad. G. Bonchev Street, bl. 26, 1113 Sofia, BulgariaDepartment of Microbiology, Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Akad. G. Bonchev Street, bl. 26, 1113 Sofia, BulgariaInstitute of Polymers, Bulgarian Academy of Sciences, Akad. G. Bonchev Street, bl. 103-A, 1113 Sofia, BulgariaInstitute of Polymers, Bulgarian Academy of Sciences, Akad. G. Bonchev Street, bl. 103-A, 1113 Sofia, BulgariaFaculty of Biology, Sofia University “St. Kliment Ohridski”, 8 Dragan Tsankov Blvd., 1164 Sofia, BulgariaNational Reference Laboratory “Control and Monitoring of Antimicrobial Resistance”, Department of Clinical Microbiology, National Center of Infectious and Parasitic Disease, Yanko Sakuzov Blvd. 26, 1504 Sofia, BulgariaFaculty of Biology, Sofia University “St. Kliment Ohridski”, 8 Dragan Tsankov Blvd., 1164 Sofia, BulgariaInstitute of Polymers, Bulgarian Academy of Sciences, Akad. G. Bonchev Street, bl. 103-A, 1113 Sofia, BulgariaDepartment of Microbiology, Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Akad. G. Bonchev Street, bl. 26, 1113 Sofia, BulgariaBiofilms are a well-known multifactorial virulence factor with a pivotal role in chronic bacterial infections. Their pathogenicity is determined by the combination of strain-specific mechanisms of virulence and the biofilm extracellular matrix (ECM) protecting the bacteria from the host immune defense and the action of antibacterials. The successful antibiofilm agents should combine antibacterial activity and good biocompatibility with the capacity to penetrate through the ECM. The objective of the study is the elaboration of biofilm-ECM-destructive drug delivery systems: mixed polymeric micelles (MPMs) based on a cationic poly(2-(dimethylamino)ethyl methacrylate)-b-poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA<sub>35</sub>-b-PCL<sub>70</sub>-b-PDMAEMA<sub>35</sub>) and a non-ionic poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO<sub>100</sub>-b-PPO<sub>65</sub>-b-PEO<sub>100</sub>) triblock copolymers, loaded with ciprofloxacin or azithromycin. The MPMs were applied on 24 h pre-formed biofilms of <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i> (laboratory strains and clinical isolates). The results showed that the MPMs were able to destruct the biofilms, and the viability experiments supported drug delivery. The biofilm response to the MPMs loaded with the two antibiotics revealed two distinct patterns of action. These were registered on the level of both bacterial cell-structural alterations (demonstrated by scanning electron microscopy) and the interaction with host tissues (ex vivo biofilm infection model on skin samples with tests on nitric oxide and interleukin (IL)-17A production).https://www.mdpi.com/2076-2607/12/12/2670biofilm destructionmixed polymer micellescationic polymersdrug deliverybiocompatibilitynanotubules |
| spellingShingle | Tsvetozara Damyanova Rumena Stancheva Milena N. Leseva Petya A. Dimitrova Tsvetelina Paunova-Krasteva Dayana Borisova Katya Kamenova Petar D. Petrov Ralitsa Veleva Ivelina Zhivkova Tanya Topouzova-Hristova Emi Haladjova Stoyanka Stoitsova Gram Negative Biofilms: Structural and Functional Responses to Destruction by Antibiotic-Loaded Mixed Polymeric Micelles Microorganisms biofilm destruction mixed polymer micelles cationic polymers drug delivery biocompatibility nanotubules |
| title | Gram Negative Biofilms: Structural and Functional Responses to Destruction by Antibiotic-Loaded Mixed Polymeric Micelles |
| title_full | Gram Negative Biofilms: Structural and Functional Responses to Destruction by Antibiotic-Loaded Mixed Polymeric Micelles |
| title_fullStr | Gram Negative Biofilms: Structural and Functional Responses to Destruction by Antibiotic-Loaded Mixed Polymeric Micelles |
| title_full_unstemmed | Gram Negative Biofilms: Structural and Functional Responses to Destruction by Antibiotic-Loaded Mixed Polymeric Micelles |
| title_short | Gram Negative Biofilms: Structural and Functional Responses to Destruction by Antibiotic-Loaded Mixed Polymeric Micelles |
| title_sort | gram negative biofilms structural and functional responses to destruction by antibiotic loaded mixed polymeric micelles |
| topic | biofilm destruction mixed polymer micelles cationic polymers drug delivery biocompatibility nanotubules |
| url | https://www.mdpi.com/2076-2607/12/12/2670 |
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