Reversal of resistance in bacteria underlies synergistic effect of essential oils with conventional antibiotics.
The pervasive of bacterial resistance earnestly threaten the prevention and the treatment of infectious diseases. Therefore, scientific communities take precedence over development of new antimicrobial agents. The aim of the study was to determine antimicrobial potency of three North-African essential oils Pituranthos chloranthus, Teucruim ramosissimum and Pistacia lentiscus individually, and in combination with antibiotics, to inhibit the growth of highly resistant clinical pathogen. Bacteria clinically isolated from patients, subsequently, challenged to a panel of drugs to determine the antibiotic-resistance profiles. Drugs displaying clinically irrelevant CMI were subjected to further studies in order to rescue antibiotic actions. Singular activity of essential oils and activity when combined with an antibiotic was hence elucidated. The results obtained highlighted the occurrence of strong antibacterial potential of essential oils when administrated alone. In the interactive experiment essential oils were found highly effective in reducing the resistance of Methicillin-resistant Staphylococcus aureus to amoxicillin, tetracycline, piperacillin, ofloxacin and oxacillin and resistance of Acinetobacter baumannii to amoxicillin and to ofloxacin in interactive manner. Furthermore, the results proved synergism among essential oils and both antibiotics ofloxacin and novobiocin against the Extended-Spectrum Beta-Lactamase producing E. coli (ESBL). Time kill kinetics was performed with a combination of sub-inhibitory concentrations to confirm the efficiency and killing rate of the combination over time. Further, the hypothetical toxicity of essential oils against human keratinocytes HaCat and murine spleenocytes were examined. The chemical composition of essential oils was assessed by GC/MS analysis and the major constituents found were sabinene, limonene, terpinen-4-ol, and β-eudesmol.
Laboratoire de Biologie Cellulaire et Moléculaire, Faculté de Médecine Dentaire, Université de Monastir, Rue Avicenne, Monastir, Tunisia; Unité de Substances Naturelles Bioactives et Biotechnologie UR12ES12, Faculté de Pharmacie de Monastir, Université de Monastir, Rue Avicenne, Monastir, Tunisia. Electronic address: elahmar.aida@gmail.com.
Aida
A
Lahmar
Laboratoire de Biologie Cellulaire et Moléculaire, Faculté de Médecine Dentaire, Université de Monastir, Rue Avicenne, Monastir, Tunisia; Unité de Substances Naturelles Bioactives et Biotechnologie UR12ES12, Faculté de Pharmacie de Monastir, Université de Monastir, Rue Avicenne, Monastir, Tunisia.
Ahmed
A
Bedoui
Laboratoire de Biologie Cellulaire et Moléculaire, Faculté de Médecine Dentaire, Université de Monastir, Rue Avicenne, Monastir, Tunisia; Unité de Substances Naturelles Bioactives et Biotechnologie UR12ES12, Faculté de Pharmacie de Monastir, Université de Monastir, Rue Avicenne, Monastir, Tunisia.
Imen
I
Mokdad-Bzeouich
Laboratoire de Biologie Cellulaire et Moléculaire, Faculté de Médecine Dentaire, Université de Monastir, Rue Avicenne, Monastir, Tunisia; Unité de Substances Naturelles Bioactives et Biotechnologie UR12ES12, Faculté de Pharmacie de Monastir, Université de Monastir, Rue Avicenne, Monastir, Tunisia.
Zaineb
Z
Dhaouifi
Laboratoire de Biologie Cellulaire et Moléculaire, Faculté de Médecine Dentaire, Université de Monastir, Rue Avicenne, Monastir, Tunisia; Unité de Substances Naturelles Bioactives et Biotechnologie UR12ES12, Faculté de Pharmacie de Monastir, Université de Monastir, Rue Avicenne, Monastir, Tunisia.
Zahar
Z
Kalboussi
Laboratoire de Biochimie, USCR de Spectrométrie de Masse, Faculté de Médecine, Université de Monastir, Tunisia.
Imed
I
Cheraif
Unité de Substances Naturelles Bioactives et Biotechnologie UR12ES12, Faculté de Pharmacie de Monastir, Université de Monastir, Rue Avicenne, Monastir, Tunisia.
Kamel
K
Ghedira
Laboratoire de Biologie Cellulaire et Moléculaire, Faculté de Médecine Dentaire, Université de Monastir, Rue Avicenne, Monastir, Tunisia; Unité de Substances Naturelles Bioactives et Biotechnologie UR12ES12, Faculté de Pharmacie de Monastir, Université de Monastir, Rue Avicenne, Monastir, Tunisia.
Leila
L
Chekir-Ghedira
D040981:Acinetobacter baumannii / Q000187:drug effects; D000658:Amoxicillin / Q000494:pharmacology; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects / Q000472:pathogenicity; D000081008:Bicyclic Monoterpenes; D002460:Cell Line / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D053138:Cyclohexenes / Q000737:chemistry; D004338:Drug Combinations; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D004357:Drug Synergism; D004926:Escherichia coli / Q000187:drug effects; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D000077222:Limonene; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests / Q000379:methods; D039821:Monoterpenes / Q000737:chemistry; D009675:Novobiocin / Q000494:pharmacology; D015242:Ofloxacin / Q000494:pharmacology; D009822:Oils, Volatile / Q000737:chemistry / Q000494:pharmacology*; D010068:Oxacillin / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D010938:Plant Oils / Q000737:chemistry / Q000494:pharmacology*; D045787:Sesquiterpenes, Eudesmane / Q000737:chemistry; D013154:Spleen / Q000187:drug effects; D013729:Terpenes / Q000737:chemistry; D013752:Tetracycline / Q000494:pharmacology; D013997:Time Factors; D001618:beta-Lactamases / Q000187:drug effects
D000890:Anti-Infective Agents; D000081008:Bicyclic Monoterpenes; D053138:Cyclohexenes; D004338:Drug Combinations; D039821:Monoterpenes; D009822:Oils, Volatile; D010936:Plant Extracts; D010938:Plant Oils; D045787:Sesquiterpenes, Eudesmane; D013729:Terpenes; D009675:Novobiocin; C051082:beta-eudesmol; C034019:terpinenol-4; C035127:sabinene; D000658:Amoxicillin; D000077222:Limonene; D015242:Ofloxacin; D001618:beta-Lactamases; D013752:Tetracycline; D010068:Oxacillin; D010878:Piperacillin
Antibiotics; Essential oil; Multi-drug-resistant bacteria; Synergism