Synergistic Activity of Colistin in Combination With Resveratrol Against Colistin-Resistant Gram-Negative Pathogens
Objectives: In this study, we investigated the antimicrobial activity of resveratrol in combination with colistin, a last-resort agent for the treatment of severe infections caused by multidrug resistant Gram-negative pathogens.Methods: The synergistic activity and the bactericidal activity of colis...
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2018-08-01
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doaj-7faaae6c46f2419ebb483c9e5a9030c42020-11-24T21:42:50ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-08-01910.3389/fmicb.2018.01808397253Synergistic Activity of Colistin in Combination With Resveratrol Against Colistin-Resistant Gram-Negative PathogensAntonio Cannatelli0Silvia Principato1Olga L. Colavecchio2Lucia Pallecchi3Gian Maria Rossolini4Gian Maria Rossolini5Department of Medical Biotechnologies, University of Siena, Siena, ItalyDepartment of Medical Biotechnologies, University of Siena, Siena, ItalySOD Genetic Diagnostic, Florence Careggi University Hospital, Florence, ItalyDepartment of Medical Biotechnologies, University of Siena, Siena, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyClinical Microbiology and Virology Unit, Florence Careggi University Hospital, Florence, ItalyObjectives: In this study, we investigated the antimicrobial activity of resveratrol in combination with colistin, a last-resort agent for the treatment of severe infections caused by multidrug resistant Gram-negative pathogens.Methods: The synergistic activity and the bactericidal activity of colistin in combination with resveratrol was investigated by checkerboard assays and time-kill assays, respectively. A total of 21 strains were investigated, including 16 strains of different species (Klebsiella pneumoniae, n = 6, Escherichia coli, n = 6; Citrobacter braakii, n = 1; Stenotrophomonas malthophilia, n = 1; Enterobacter cloaceae, n = 1; Acinetobacter baumannii, n = 1) with acquired colistin resistance, three colistin-susceptible K. pneumoniae precursors, and two strains of intrinsically colistin-resistant species (Serratia marcescens, n = 1; Proteus mirabilis, n = 1). Mechanisms of acquired colistin resistance included chromosomal mutations (i.e., mgrB, pmrAB) and plasmid genes (mcr-1, mcr-1.2).Results: Resveratrol did not show any significant intrinsic antimicrobial activity. Overall, a relevant synergistic antimicrobial activity of resveratrol in combination with colistin was observed with all tested strains, except for the three colistin-susceptible K. pneumoniae strains, and for two mcr-1-positive E. coli strains. In time-kill assays, performed with 15 selected strains, the combination of colistin 2 mg/L plus resveratrol 128 mg/L was bactericidal with 11 strains, and bacteriostatic for the remaining ones.Conclusions: Resveratrol was found to potentiate colistin activity against a wide panel of colistin-resistant strains, regardless of species and resistance mechanisms, which would deserve further investigation for potential clinical applications.https://www.frontiersin.org/article/10.3389/fmicb.2018.01808/fullcolistinresveratrolcolistin resistanceantibiotic resistance breakerscombination therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Antonio Cannatelli Silvia Principato Olga L. Colavecchio Lucia Pallecchi Gian Maria Rossolini Gian Maria Rossolini |
spellingShingle |
Antonio Cannatelli Silvia Principato Olga L. Colavecchio Lucia Pallecchi Gian Maria Rossolini Gian Maria Rossolini Synergistic Activity of Colistin in Combination With Resveratrol Against Colistin-Resistant Gram-Negative Pathogens Frontiers in Microbiology colistin resveratrol colistin resistance antibiotic resistance breakers combination therapy |
author_facet |
Antonio Cannatelli Silvia Principato Olga L. Colavecchio Lucia Pallecchi Gian Maria Rossolini Gian Maria Rossolini |
author_sort |
Antonio Cannatelli |
title |
Synergistic Activity of Colistin in Combination With Resveratrol Against Colistin-Resistant Gram-Negative Pathogens |
title_short |
Synergistic Activity of Colistin in Combination With Resveratrol Against Colistin-Resistant Gram-Negative Pathogens |
title_full |
Synergistic Activity of Colistin in Combination With Resveratrol Against Colistin-Resistant Gram-Negative Pathogens |
title_fullStr |
Synergistic Activity of Colistin in Combination With Resveratrol Against Colistin-Resistant Gram-Negative Pathogens |
title_full_unstemmed |
Synergistic Activity of Colistin in Combination With Resveratrol Against Colistin-Resistant Gram-Negative Pathogens |
title_sort |
synergistic activity of colistin in combination with resveratrol against colistin-resistant gram-negative pathogens |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Microbiology |
issn |
1664-302X |
publishDate |
2018-08-01 |
description |
Objectives: In this study, we investigated the antimicrobial activity of resveratrol in combination with colistin, a last-resort agent for the treatment of severe infections caused by multidrug resistant Gram-negative pathogens.Methods: The synergistic activity and the bactericidal activity of colistin in combination with resveratrol was investigated by checkerboard assays and time-kill assays, respectively. A total of 21 strains were investigated, including 16 strains of different species (Klebsiella pneumoniae, n = 6, Escherichia coli, n = 6; Citrobacter braakii, n = 1; Stenotrophomonas malthophilia, n = 1; Enterobacter cloaceae, n = 1; Acinetobacter baumannii, n = 1) with acquired colistin resistance, three colistin-susceptible K. pneumoniae precursors, and two strains of intrinsically colistin-resistant species (Serratia marcescens, n = 1; Proteus mirabilis, n = 1). Mechanisms of acquired colistin resistance included chromosomal mutations (i.e., mgrB, pmrAB) and plasmid genes (mcr-1, mcr-1.2).Results: Resveratrol did not show any significant intrinsic antimicrobial activity. Overall, a relevant synergistic antimicrobial activity of resveratrol in combination with colistin was observed with all tested strains, except for the three colistin-susceptible K. pneumoniae strains, and for two mcr-1-positive E. coli strains. In time-kill assays, performed with 15 selected strains, the combination of colistin 2 mg/L plus resveratrol 128 mg/L was bactericidal with 11 strains, and bacteriostatic for the remaining ones.Conclusions: Resveratrol was found to potentiate colistin activity against a wide panel of colistin-resistant strains, regardless of species and resistance mechanisms, which would deserve further investigation for potential clinical applications. |
topic |
colistin resveratrol colistin resistance antibiotic resistance breakers combination therapy |
url |
https://www.frontiersin.org/article/10.3389/fmicb.2018.01808/full |
work_keys_str_mv |
AT antoniocannatelli synergisticactivityofcolistinincombinationwithresveratrolagainstcolistinresistantgramnegativepathogens AT silviaprincipato synergisticactivityofcolistinincombinationwithresveratrolagainstcolistinresistantgramnegativepathogens AT olgalcolavecchio synergisticactivityofcolistinincombinationwithresveratrolagainstcolistinresistantgramnegativepathogens AT luciapallecchi synergisticactivityofcolistinincombinationwithresveratrolagainstcolistinresistantgramnegativepathogens AT gianmariarossolini synergisticactivityofcolistinincombinationwithresveratrolagainstcolistinresistantgramnegativepathogens AT gianmariarossolini synergisticactivityofcolistinincombinationwithresveratrolagainstcolistinresistantgramnegativepathogens |
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