title: Adaptation of Salmonella enterica Serovar Senftenberg to Linalool and Its Association with Antibiotic Resistance and Environmental Persistence.
abstract: A clinical isolate ofSalmonella entericaserovar Senftenberg, isolated from an outbreak linked to the herbOcimum basilicumL. (basil), has been shown to be resistant to basil oil and to the terpene alcohol linalool. To better understand how human pathogens might develop resistance to linalool and to investigate the association of this resistance with resistance to different antimicrobial agents, selective pressure was applied to the wild-type strain by sequential exposure to increasing concentrations of linalool. The results demonstrated thatSSenftenberg adapted to linalool with a MIC increment of at least 8-fold, which also resulted in better resistance to basil oil and better survival on harvested basil leaves. Adaptation to linalool was shown to confer cross protection against the antibiotics trimethoprim, sulfamethoxazole, piperacillin, chloramphenicol, and tetracycline, increasing their MICs by 2- to 32-fold. The improved resistance was shown to correlate with multiple phenotypes that included changes in membrane fatty acid composition, induced efflux, reduced influx, controlled motility, and the ability to form larger aggregates in the presence of linalool. The adaptation to linalool obtainedin vitrodid not affect survival on the basil phyllospherein plantaand even diminished survival in soil, suggesting that development of extreme resistance to linalool may be accompanied by a loss of fitness. Altogether, this report notes the concern regarding the ability of human pathogens to develop resistance to commercial essential oils, a resistance that is also associated with cross-resistance to antibiotics and may endanger public health.IMPORTANCEGreater consumer awareness and concern regarding synthetic chemical additives have led producers to control microbial spoilage and hazards by the use of natural preservatives, such as plant essential oils with antimicrobial activity. This report establishes, however, that these compounds may provoke the emergence of resistant human pathogens. Herein, we demonstrate the acquisition of resistance to basil oil bySalmonellaSenftenberg. Exposure to linalool, a component of basil oil, resulted in adaptation to the basil oil mixture, as well as cross protection against several antibiotics and better survival on harvested basil leaves. Collectively, this work highlights the hazard to public health while using plant essential oils without sufficient knowledge about their influence on pathogens at subinhibitory concentrations.
authors.affiliation: Faculty of Biotechnology and Food Engineering and the Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Kalily
authors.affiliation: Faculty of Biotechnology and Food Engineering and the Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Amit
authors.identifier: http://orcid.org/0000-0002-6972-8177
authors.initials: A
authors.lastname: Hollander
authors.affiliation: Faculty of Biotechnology and Food Engineering and the Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Ben
authors.initials: B
authors.lastname: Korin
authors.affiliation: Faculty of Biotechnology and Food Engineering and the Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Itamar
authors.initials: I
authors.lastname: Cymerman
authors.affiliation: Faculty of Biotechnology and Food Engineering and the Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology, Haifa, Israel simay@tx.technion.ac.il.
authors.forename: Sima
authors.initials: S
authors.lastname: Yaron
mesh_terms: D000080462:Acyclic Monoterpenes; D000222:Adaptation, Physiological; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002701:Chloramphenicol / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D008826:Microbial Sensitivity Tests; D039821:Monoterpenes / Q000494:pharmacology*; D018649:Ocimum basilicum / Q000737:chemistry* / Q000382:microbiology; D009822:Oils, Volatile / Q000494:pharmacology*; D010878:Piperacillin / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry / Q000382:microbiology; D019779:Salmonella enterica / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D013420:Sulfamethoxazole / Q000494:pharmacology
chemical_list: D000080462:Acyclic Monoterpenes; D000900:Anti-Bacterial Agents; D039821:Monoterpenes; D009822:Oils, Volatile; D002701:Chloramphenicol; C018584:linalool; D013420:Sulfamethoxazole; D010878:Piperacillin
keywords: antibiotic resistance; essential oils; foodborne pathogens; host-pathogen interactions