Conjugation of LasR Quorum-Sensing Inhibitors with Ciprofloxacin Decreases the Antibiotic Tolerance of P. aeruginosa Clinical Strains
Pseudomonas aeruginosa is a Gram-negative bacterium that commonly infects subjects with weakened immune system causing deadly infections above all at pulmonary level. During infection, P. aeruginosa produces a well-organized bacterial structure, called biofilm, activating the quorum-sensing (QS) sig...
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| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2019/8143739 |
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| author | Daria Bortolotti Claudio Trapella Alessandra Bragonzi Paolo Marchetti Vinicio Zanirato Andrea Alogna Valentina Gentili Carlo Cervellati Giuseppe Valacchi Mariangela Sicolo Giulia Turrin Anna Fantinati Dario Di Luca Roberta Rizzo |
| author_facet | Daria Bortolotti Claudio Trapella Alessandra Bragonzi Paolo Marchetti Vinicio Zanirato Andrea Alogna Valentina Gentili Carlo Cervellati Giuseppe Valacchi Mariangela Sicolo Giulia Turrin Anna Fantinati Dario Di Luca Roberta Rizzo |
| author_sort | Daria Bortolotti |
| collection | DOAJ |
| description | Pseudomonas aeruginosa is a Gram-negative bacterium that commonly infects subjects with weakened immune system causing deadly infections above all at pulmonary level. During infection, P. aeruginosa produces a well-organized bacterial structure, called biofilm, activating the quorum-sensing (QS) signaling, a mechanism of gene regulation. In this work, we synthesized already known QS inhibitors (QSi) designed on the scaffold of the N-(3-oxododecanoyl) homoserine lactone (3O-C12-HSL) QS molecule and conjugated them with ciprofloxacin to inhibit P. aeruginosa biofilm formation and increase the antibiotic susceptibility of clinical strains. We identified, for the first time, a QSi conjugated with ciprofloxacin (ET37), that is able to reduce the formation of biofilm and the onset of tolerant clones in P. aeruginosa clinical strains. This compound could have a wide application in clinical setting. The possibility to affect biofilm formation in chronically infected patients, such as patients affected by cystic fibrosis, and to reduce the onset of ciprofloxacin resistance would improve patient healing and allow to decrease antibiotic drug dosage. |
| format | Article |
| id | doaj-art-7d5e20291ab4411d85e1eb255ab73610 |
| institution | Kabale University |
| issn | 2090-9063 2090-9071 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Chemistry |
| spelling | doaj-art-7d5e20291ab4411d85e1eb255ab736102025-02-03T01:03:35ZengWileyJournal of Chemistry2090-90632090-90712019-01-01201910.1155/2019/81437398143739Conjugation of LasR Quorum-Sensing Inhibitors with Ciprofloxacin Decreases the Antibiotic Tolerance of P. aeruginosa Clinical StrainsDaria Bortolotti0Claudio Trapella1Alessandra Bragonzi2Paolo Marchetti3Vinicio Zanirato4Andrea Alogna5Valentina Gentili6Carlo Cervellati7Giuseppe Valacchi8Mariangela Sicolo9Giulia Turrin10Anna Fantinati11Dario Di Luca12Roberta Rizzo13Department of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, Via Luigi Borsari, 46-44121 Ferrara, ItalyDepartment of Chemical and Pharmaceutical Sciences, University of Ferrara, Via Fossato di Mortara, 17, 44121 Ferrara, ItalyDivision of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milano, ItalyDepartment of Chemical and Pharmaceutical Sciences, University of Ferrara, Via Fossato di Mortara, 17, 44121 Ferrara, ItalyDepartment of Chemical and Pharmaceutical Sciences, University of Ferrara, Via Fossato di Mortara, 17, 44121 Ferrara, ItalyDepartment of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, Via Luigi Borsari, 46-44121 Ferrara, ItalyDepartment of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, Via Luigi Borsari, 46-44121 Ferrara, ItalyDepartment of Biomedical and Specialist Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics, University of Ferrara, Via Luigi Borsari, 46-44121 Ferrara, ItalyDepartment of Life Sciences and Biotechnology, Section of Biology and Evolution, University of Ferrara, Via Luigi Borsari, 46-44121 Ferrara, ItalyDepartment of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, Via Luigi Borsari, 46-44121 Ferrara, ItalyDepartment of Chemical and Pharmaceutical Sciences, University of Ferrara, Via Fossato di Mortara, 17, 44121 Ferrara, ItalyDepartment of Chemical and Pharmaceutical Sciences, University of Ferrara, Via Fossato di Mortara, 17, 44121 Ferrara, ItalyDepartment of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, Via Luigi Borsari, 46-44121 Ferrara, ItalyDepartment of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, Via Luigi Borsari, 46-44121 Ferrara, ItalyPseudomonas aeruginosa is a Gram-negative bacterium that commonly infects subjects with weakened immune system causing deadly infections above all at pulmonary level. During infection, P. aeruginosa produces a well-organized bacterial structure, called biofilm, activating the quorum-sensing (QS) signaling, a mechanism of gene regulation. In this work, we synthesized already known QS inhibitors (QSi) designed on the scaffold of the N-(3-oxododecanoyl) homoserine lactone (3O-C12-HSL) QS molecule and conjugated them with ciprofloxacin to inhibit P. aeruginosa biofilm formation and increase the antibiotic susceptibility of clinical strains. We identified, for the first time, a QSi conjugated with ciprofloxacin (ET37), that is able to reduce the formation of biofilm and the onset of tolerant clones in P. aeruginosa clinical strains. This compound could have a wide application in clinical setting. The possibility to affect biofilm formation in chronically infected patients, such as patients affected by cystic fibrosis, and to reduce the onset of ciprofloxacin resistance would improve patient healing and allow to decrease antibiotic drug dosage.http://dx.doi.org/10.1155/2019/8143739 |
| spellingShingle | Daria Bortolotti Claudio Trapella Alessandra Bragonzi Paolo Marchetti Vinicio Zanirato Andrea Alogna Valentina Gentili Carlo Cervellati Giuseppe Valacchi Mariangela Sicolo Giulia Turrin Anna Fantinati Dario Di Luca Roberta Rizzo Conjugation of LasR Quorum-Sensing Inhibitors with Ciprofloxacin Decreases the Antibiotic Tolerance of P. aeruginosa Clinical Strains Journal of Chemistry |
| title | Conjugation of LasR Quorum-Sensing Inhibitors with Ciprofloxacin Decreases the Antibiotic Tolerance of P. aeruginosa Clinical Strains |
| title_full | Conjugation of LasR Quorum-Sensing Inhibitors with Ciprofloxacin Decreases the Antibiotic Tolerance of P. aeruginosa Clinical Strains |
| title_fullStr | Conjugation of LasR Quorum-Sensing Inhibitors with Ciprofloxacin Decreases the Antibiotic Tolerance of P. aeruginosa Clinical Strains |
| title_full_unstemmed | Conjugation of LasR Quorum-Sensing Inhibitors with Ciprofloxacin Decreases the Antibiotic Tolerance of P. aeruginosa Clinical Strains |
| title_short | Conjugation of LasR Quorum-Sensing Inhibitors with Ciprofloxacin Decreases the Antibiotic Tolerance of P. aeruginosa Clinical Strains |
| title_sort | conjugation of lasr quorum sensing inhibitors with ciprofloxacin decreases the antibiotic tolerance of p aeruginosa clinical strains |
| url | http://dx.doi.org/10.1155/2019/8143739 |
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