Antivirulence Properties of a Low-Molecular-Weight Quaternized Chitosan Derivative against <i>Pseudomonas aeruginosa</i>
The co-occurrence of increasing rates of resistance to current antibiotics and the paucity of novel antibiotics pose major challenges for the treatment of bacterial infections. In this scenario, treatments targeting bacterial virulence have gained considerable interest as they are expected to exert...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/9/5/912 |
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| author | Giuseppantonio Maisetta Anna Maria Piras Vincenzo Motta Simona Braccini Diletta Mazzantini Federica Chiellini Ylenia Zambito Semih Esin Giovanna Batoni |
| author_facet | Giuseppantonio Maisetta Anna Maria Piras Vincenzo Motta Simona Braccini Diletta Mazzantini Federica Chiellini Ylenia Zambito Semih Esin Giovanna Batoni |
| author_sort | Giuseppantonio Maisetta |
| collection | DOAJ |
| description | The co-occurrence of increasing rates of resistance to current antibiotics and the paucity of novel antibiotics pose major challenges for the treatment of bacterial infections. In this scenario, treatments targeting bacterial virulence have gained considerable interest as they are expected to exert a weaker selection for resistance than conventional antibiotics. In a previous study, we demonstrated that a low-molecular-weight quaternized chitosan derivative, named QAL, displays antibiofilm activity against the major pathogen <i>Pseudomonas aeruginosa</i> at subinhibitory concentrations. The aim of this study was to investigate whether QAL was able to inhibit the production of relevant virulence factors of <i>P. aeruginosa</i>. When tested in vitro at subinhibiting concentrations (0.31–0.62 mg/mL), QAL markedly reduced the production of pyocyanin, pyoverdin, proteases, and LasA, as well as inhibited the swarming motility of three out of four <i>P. aeruginosa</i> strains tested. Furthermore, quantitative reverse transcription PCR (qRT-PCR) analyses demonstrated that expression of <i>lasI</i> and <i>rhlI</i>, two QS-related genes, was highly downregulated in a representative <i>P. aeruginosa</i> strain. Confocal scanning laser microscopy analysis suggested that FITC-labelled QAL accumulates intracellularly following incubation with <i>P. aeruginosa</i>. In contrast, the reduced production of virulence factors was not evidenced when QAL was used as the main polymeric component of polyelectrolyte-based nanoparticles. Additionally, combination of sub-MIC concentrations of QAL and tobramycin significantly reduced biofilm formation of <i>P. aeruginosa</i>, likely due to a synergistic activity towards planktonic bacteria. Overall, the results obtained demonstrated an antivirulence activity of QAL, possibly due to polymer intracellular localization and QS-inhibition, and its ability to inhibit <i>P. aeruginosa</i> growth synergizing with tobramycin. |
| first_indexed | 2024-03-10T12:00:28Z |
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| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T12:00:28Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
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| series | Microorganisms |
| spelling | doaj.art-0873a64365a24217a03d066c48e1dd7a2023-11-21T16:59:35ZengMDPI AGMicroorganisms2076-26072021-04-019591210.3390/microorganisms9050912Antivirulence Properties of a Low-Molecular-Weight Quaternized Chitosan Derivative against <i>Pseudomonas aeruginosa</i>Giuseppantonio Maisetta0Anna Maria Piras1Vincenzo Motta2Simona Braccini3Diletta Mazzantini4Federica Chiellini5Ylenia Zambito6Semih Esin7Giovanna Batoni8Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyDepartment of Chemistry and Industrial Chemistry, University of Pisa, UdR INSTM PISA, 56124 Pisa, ItalyDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyDepartment of Chemistry and Industrial Chemistry, University of Pisa, UdR INSTM PISA, 56124 Pisa, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyThe co-occurrence of increasing rates of resistance to current antibiotics and the paucity of novel antibiotics pose major challenges for the treatment of bacterial infections. In this scenario, treatments targeting bacterial virulence have gained considerable interest as they are expected to exert a weaker selection for resistance than conventional antibiotics. In a previous study, we demonstrated that a low-molecular-weight quaternized chitosan derivative, named QAL, displays antibiofilm activity against the major pathogen <i>Pseudomonas aeruginosa</i> at subinhibitory concentrations. The aim of this study was to investigate whether QAL was able to inhibit the production of relevant virulence factors of <i>P. aeruginosa</i>. When tested in vitro at subinhibiting concentrations (0.31–0.62 mg/mL), QAL markedly reduced the production of pyocyanin, pyoverdin, proteases, and LasA, as well as inhibited the swarming motility of three out of four <i>P. aeruginosa</i> strains tested. Furthermore, quantitative reverse transcription PCR (qRT-PCR) analyses demonstrated that expression of <i>lasI</i> and <i>rhlI</i>, two QS-related genes, was highly downregulated in a representative <i>P. aeruginosa</i> strain. Confocal scanning laser microscopy analysis suggested that FITC-labelled QAL accumulates intracellularly following incubation with <i>P. aeruginosa</i>. In contrast, the reduced production of virulence factors was not evidenced when QAL was used as the main polymeric component of polyelectrolyte-based nanoparticles. Additionally, combination of sub-MIC concentrations of QAL and tobramycin significantly reduced biofilm formation of <i>P. aeruginosa</i>, likely due to a synergistic activity towards planktonic bacteria. Overall, the results obtained demonstrated an antivirulence activity of QAL, possibly due to polymer intracellular localization and QS-inhibition, and its ability to inhibit <i>P. aeruginosa</i> growth synergizing with tobramycin.https://www.mdpi.com/2076-2607/9/5/912chitosanquaternized chitosan<i>Pseudomonas aeruginosa</i>pyocyaninpyoverdinproteases |
| spellingShingle | Giuseppantonio Maisetta Anna Maria Piras Vincenzo Motta Simona Braccini Diletta Mazzantini Federica Chiellini Ylenia Zambito Semih Esin Giovanna Batoni Antivirulence Properties of a Low-Molecular-Weight Quaternized Chitosan Derivative against <i>Pseudomonas aeruginosa</i> Microorganisms chitosan quaternized chitosan <i>Pseudomonas aeruginosa</i> pyocyanin pyoverdin proteases |
| title | Antivirulence Properties of a Low-Molecular-Weight Quaternized Chitosan Derivative against <i>Pseudomonas aeruginosa</i> |
| title_full | Antivirulence Properties of a Low-Molecular-Weight Quaternized Chitosan Derivative against <i>Pseudomonas aeruginosa</i> |
| title_fullStr | Antivirulence Properties of a Low-Molecular-Weight Quaternized Chitosan Derivative against <i>Pseudomonas aeruginosa</i> |
| title_full_unstemmed | Antivirulence Properties of a Low-Molecular-Weight Quaternized Chitosan Derivative against <i>Pseudomonas aeruginosa</i> |
| title_short | Antivirulence Properties of a Low-Molecular-Weight Quaternized Chitosan Derivative against <i>Pseudomonas aeruginosa</i> |
| title_sort | antivirulence properties of a low molecular weight quaternized chitosan derivative against i pseudomonas aeruginosa i |
| topic | chitosan quaternized chitosan <i>Pseudomonas aeruginosa</i> pyocyanin pyoverdin proteases |
| url | https://www.mdpi.com/2076-2607/9/5/912 |
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