The antimicrobial peptide Esc(1-21)-1c increases susceptibility of Pseudomonas aeruginosa to conventional antibiotics by decreasing the expression of the MexAB-OprM efflux pump
Introduction: The increase in bacterial strains resistant to conventional antibiotics is an alarming problem for human health and could lead to pandemics in the future. Among bacterial pathogens responsible for a large variety of severe infections there is Pseudomonas aeruginosa. Therefore, there is...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2023.1271153/full |
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| author | Carolina Canè Bruno Casciaro Angela Di Somma Angela Di Somma Maria Rosa Loffredo Elena Puglisi Gennaro Battaglia Marta Mellini Floriana Cappiello Giordano Rampioni Giordano Rampioni Livia Leoni Angela Amoresano Angela Amoresano Angela Duilio Angela Duilio Maria Luisa Mangoni |
| author_facet | Carolina Canè Bruno Casciaro Angela Di Somma Angela Di Somma Maria Rosa Loffredo Elena Puglisi Gennaro Battaglia Marta Mellini Floriana Cappiello Giordano Rampioni Giordano Rampioni Livia Leoni Angela Amoresano Angela Amoresano Angela Duilio Angela Duilio Maria Luisa Mangoni |
| author_sort | Carolina Canè |
| collection | DOAJ |
| description | Introduction: The increase in bacterial strains resistant to conventional antibiotics is an alarming problem for human health and could lead to pandemics in the future. Among bacterial pathogens responsible for a large variety of severe infections there is Pseudomonas aeruginosa. Therefore, there is an urgent need for new molecules with antimicrobial activity or that can act as adjuvants of antibiotics already in use. In this scenario, antimicrobial peptides (AMPs) hold great promise. Recently, we characterized a frog-skin AMP derived from esculentin-1a, namely Esc(1-21)-1c, endowed with antipseudomonal activity without being cytotoxic to human cells.Methods: The combinatorial effect of the peptide and antibiotics was investigated through the checkerboard assay, differential proteomic and transcriptional analysis.Results: Here, we found that Esc(1-21)-1c can synergistically inhibit the growth of P. aeruginosa cells with three different antibiotics, including tetracycline. We therefore investigated the underlying mechanism implemented by the peptide using a differential proteomic approach. The data revealed a significant decrease in the production of three proteins belonging to the MexAB-OprM efflux pump upon treatment with sub-inhibitory concentration of Esc(1-21)-1c. Down-regulation of these proteins was confirmed by transcriptional analysis and direct measurement of their relative levels in bacterial cells by tandem mass spectrometry analysis in multiple reaction monitoring scan mode.Conclusion: These evidences suggest that treatment with Esc(1-21)-1c in combination with antibiotics would increase the intracellular drug content making bacteria more susceptible to the antibiotic. Overall, these results highlight the importance of characterizing new molecules able to synergize with conventional antibiotics, paving the way for the development of alternative therapeutic strategies based on AMP/antibiotic formulations to counteract the emergence of resistant bacterial strains and increase the use of “old” antibiotics in medical practice. |
| first_indexed | 2024-03-11T16:04:23Z |
| format | Article |
| id | doaj.art-bf8dad2de28a4e588ebe6708eca19b7b |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-03-11T16:04:23Z |
| publishDate | 2023-10-01 |
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| series | Frontiers in Chemistry |
| spelling | doaj.art-bf8dad2de28a4e588ebe6708eca19b7b2023-10-25T06:13:57ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462023-10-011110.3389/fchem.2023.12711531271153The antimicrobial peptide Esc(1-21)-1c increases susceptibility of Pseudomonas aeruginosa to conventional antibiotics by decreasing the expression of the MexAB-OprM efflux pumpCarolina Canè0Bruno Casciaro1Angela Di Somma2Angela Di Somma3Maria Rosa Loffredo4Elena Puglisi5Gennaro Battaglia6Marta Mellini7Floriana Cappiello8Giordano Rampioni9Giordano Rampioni10Livia Leoni11Angela Amoresano12Angela Amoresano13Angela Duilio14Angela Duilio15Maria Luisa Mangoni16Department of Chemical Sciences, University of Naples “Federico II”, Naples, ItalyLaboratory Affiliated to Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, Rome, ItalyDepartment of Chemical Sciences, University of Naples “Federico II”, Naples, ItalyCEINGE Biotecnologie Avanzate, Naples, ItalyLaboratory Affiliated to Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, Rome, ItalyLaboratory Affiliated to Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, Rome, ItalyDepartment of Chemical Sciences, University of Naples “Federico II”, Naples, ItalyDepartment of Science, University “Roma Tre”, Rome, ItalyLaboratory Affiliated to Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, Rome, ItalyDepartment of Science, University “Roma Tre”, Rome, ItalyIRCCS Fondazione Santa Lucia, Rome, ItalyDepartment of Science, University “Roma Tre”, Rome, ItalyDepartment of Chemical Sciences, University of Naples “Federico II”, Naples, ItalyNational Institute of Biostructure and Biosystems (INBB), Rome, ItalyDepartment of Chemical Sciences, University of Naples “Federico II”, Naples, ItalyNational Institute of Biostructure and Biosystems (INBB), Rome, ItalyLaboratory Affiliated to Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, Rome, ItalyIntroduction: The increase in bacterial strains resistant to conventional antibiotics is an alarming problem for human health and could lead to pandemics in the future. Among bacterial pathogens responsible for a large variety of severe infections there is Pseudomonas aeruginosa. Therefore, there is an urgent need for new molecules with antimicrobial activity or that can act as adjuvants of antibiotics already in use. In this scenario, antimicrobial peptides (AMPs) hold great promise. Recently, we characterized a frog-skin AMP derived from esculentin-1a, namely Esc(1-21)-1c, endowed with antipseudomonal activity without being cytotoxic to human cells.Methods: The combinatorial effect of the peptide and antibiotics was investigated through the checkerboard assay, differential proteomic and transcriptional analysis.Results: Here, we found that Esc(1-21)-1c can synergistically inhibit the growth of P. aeruginosa cells with three different antibiotics, including tetracycline. We therefore investigated the underlying mechanism implemented by the peptide using a differential proteomic approach. The data revealed a significant decrease in the production of three proteins belonging to the MexAB-OprM efflux pump upon treatment with sub-inhibitory concentration of Esc(1-21)-1c. Down-regulation of these proteins was confirmed by transcriptional analysis and direct measurement of their relative levels in bacterial cells by tandem mass spectrometry analysis in multiple reaction monitoring scan mode.Conclusion: These evidences suggest that treatment with Esc(1-21)-1c in combination with antibiotics would increase the intracellular drug content making bacteria more susceptible to the antibiotic. Overall, these results highlight the importance of characterizing new molecules able to synergize with conventional antibiotics, paving the way for the development of alternative therapeutic strategies based on AMP/antibiotic formulations to counteract the emergence of resistant bacterial strains and increase the use of “old” antibiotics in medical practice.https://www.frontiersin.org/articles/10.3389/fchem.2023.1271153/fullPseudomonas aeruginosaantimicrobial peptideantibioticstetracyclineefflux pumpsproteomic |
| spellingShingle | Carolina Canè Bruno Casciaro Angela Di Somma Angela Di Somma Maria Rosa Loffredo Elena Puglisi Gennaro Battaglia Marta Mellini Floriana Cappiello Giordano Rampioni Giordano Rampioni Livia Leoni Angela Amoresano Angela Amoresano Angela Duilio Angela Duilio Maria Luisa Mangoni The antimicrobial peptide Esc(1-21)-1c increases susceptibility of Pseudomonas aeruginosa to conventional antibiotics by decreasing the expression of the MexAB-OprM efflux pump Frontiers in Chemistry Pseudomonas aeruginosa antimicrobial peptide antibiotics tetracycline efflux pumps proteomic |
| title | The antimicrobial peptide Esc(1-21)-1c increases susceptibility of Pseudomonas aeruginosa to conventional antibiotics by decreasing the expression of the MexAB-OprM efflux pump |
| title_full | The antimicrobial peptide Esc(1-21)-1c increases susceptibility of Pseudomonas aeruginosa to conventional antibiotics by decreasing the expression of the MexAB-OprM efflux pump |
| title_fullStr | The antimicrobial peptide Esc(1-21)-1c increases susceptibility of Pseudomonas aeruginosa to conventional antibiotics by decreasing the expression of the MexAB-OprM efflux pump |
| title_full_unstemmed | The antimicrobial peptide Esc(1-21)-1c increases susceptibility of Pseudomonas aeruginosa to conventional antibiotics by decreasing the expression of the MexAB-OprM efflux pump |
| title_short | The antimicrobial peptide Esc(1-21)-1c increases susceptibility of Pseudomonas aeruginosa to conventional antibiotics by decreasing the expression of the MexAB-OprM efflux pump |
| title_sort | antimicrobial peptide esc 1 21 1c increases susceptibility of pseudomonas aeruginosa to conventional antibiotics by decreasing the expression of the mexab oprm efflux pump |
| topic | Pseudomonas aeruginosa antimicrobial peptide antibiotics tetracycline efflux pumps proteomic |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2023.1271153/full |
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