title: Resistance-nodulation-division efflux pump acrAB is modulated by florfenicol and contributes to drug resistance in the fish pathogen Piscirickettsia salmonis.
abstract: Piscirickettsia salmonis is a fastidious intracellular pathogen responsible for high mortality rates in farmed salmonids, with serious economic consequences for the Chilean aquaculture industry. Oxytetracycline and florfenicol are the most frequently used antibiotics against P. salmonis, but routine use could contribute to drug resistance. This study identified differentiated florfenicol susceptibilities in two P. salmonis strains, LF-89 and AUSTRAL-005. The less susceptible isolate, AUSTRAL-005, also showed a high ethidium bromide efflux rate, indicating a higher activity of general efflux pump genes than LF-89. The P. salmonis genome presented resistance nodulation division (RND) family members, a family containing typical multidrug resistance-related efflux pumps in Gram-negative bacteria. Additionally, efflux pump acrAB genes were overexpressed in AUSTRAL-005 following exposure to the tolerated maximal concentration of florfenicol, in contrast to LF-89. These results indicate that tolerated maximum concentrations of florfenicol can modulate RND gene expression and increase efflux pump activity. We propose that the acrAB efflux pump is essential for P. salmonis survival at critical florfenicol concentrations and for the generation of antibiotic-resistant bacterial strains.
authors.affiliation: Department of Biochemistry and Microbiology, Faculty of Sciences, Universidad Austral de Chile, Campus Isla Teja, Valdivia 5090000, Chile.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Sandoval
authors.affiliation: Department of Biochemistry and Microbiology, Faculty of Sciences, Universidad Austral de Chile, Campus Isla Teja, Valdivia 5090000, Chile Department of Biological Sciences, Faculty of Biological Sciences, Universidad Andrés Bello, Santiago 8370146, Chile Interdisciplinary Center for Aquaculture Research (INCAR), Concepción 4030000, Chile.
authors.forename: Cristian
authors.initials: C
authors.lastname: Oliver
authors.affiliation: Department of Biochemistry and Microbiology, Faculty of Sciences, Universidad Austral de Chile, Campus Isla Teja, Valdivia 5090000, Chile.
authors.forename: Sharin
authors.initials: S
authors.lastname: Valdivia
authors.affiliation: Department of Biochemistry and Microbiology, Faculty of Sciences, Universidad Austral de Chile, Campus Isla Teja, Valdivia 5090000, Chile Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada.
authors.forename: Karla
authors.initials: K
authors.lastname: Valenzuela
authors.affiliation: Department of Biochemistry and Microbiology, Faculty of Sciences, Universidad Austral de Chile, Campus Isla Teja, Valdivia 5090000, Chile.
authors.forename: Ronie E
authors.initials: RE
authors.lastname: Haro
authors.affiliation: Department of Biochemistry and Microbiology, Faculty of Sciences, Universidad Austral de Chile, Campus Isla Teja, Valdivia 5090000, Chile Interdisciplinary Center for Aquaculture Research (INCAR), Concepción 4030000, Chile.
authors.forename: Patricio
authors.initials: P
authors.lastname: Sánchez
authors.affiliation: Department of Biochemistry and Microbiology, Faculty of Sciences, Universidad Austral de Chile, Campus Isla Teja, Valdivia 5090000, Chile.
authors.forename: Víctor H
authors.initials: VH
authors.lastname: Olavarría
authors.affiliation: Department of Biochemistry and Microbiology, Faculty of Sciences, Universidad Austral de Chile, Campus Isla Teja, Valdivia 5090000, Chile.
authors.forename: Paulina
authors.initials: P
authors.lastname: Valenzuela
authors.affiliation: Department of Biological Sciences, Faculty of Biological Sciences, Universidad Andrés Bello, Santiago 8370146, Chile Interdisciplinary Center for Aquaculture Research (INCAR), Concepción 4030000, Chile.
authors.forename: Rubén
authors.initials: R
authors.lastname: Avendaño-Herrera
authors.affiliation: Interdisciplinary Center for Aquaculture Research (INCAR), Concepción 4030000, Chile Department of Animal Pathology, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile.
authors.forename: Alex
authors.initials: A
authors.lastname: Romero
authors.affiliation: Department of Biochemistry and Microbiology, Faculty of Sciences, Universidad Austral de Chile, Campus Isla Teja, Valdivia 5090000, Chile Interdisciplinary Center for Aquaculture Research (INCAR), Concepción 4030000, Chile.
authors.forename: Juan G
authors.initials: JG
authors.lastname: Cárcamo
authors.affiliation: Department of Biochemistry and Microbiology, Faculty of Sciences, Universidad Austral de Chile, Campus Isla Teja, Valdivia 5090000, Chile Interdisciplinary Center for Aquaculture Research (INCAR), Concepción 4030000, Chile.
authors.forename: Jaime E
authors.initials: JE
authors.lastname: Figueroa
authors.affiliation: Department of Biochemistry and Microbiology, Faculty of Sciences, Universidad Austral de Chile, Campus Isla Teja, Valdivia 5090000, Chile Interdisciplinary Center for Aquaculture Research (INCAR), Concepción 4030000, Chile Austral-OMICS, Faculty of Sciences, Universidad Austral de Chile, Campus Isla Tela, Valdivia 5090000, Chile ayanez@uach.cl.
authors.forename: Alejandro J
authors.initials: AJ
authors.lastname: Yáñez
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017756:Aquaculture; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002677:Chile; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D004996:Ethidium / Q000378:metabolism; D005399:Fishes / Q000382:microbiology*; D019450:Genes, MDR; D016680:Genome, Bacterial; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D053522:Piscirickettsia / Q000187:drug effects* / Q000235:genetics* / Q000472:pathogenicity; D013839:Thiamphenicol / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; C035534:florfenicol; D004996:Ethidium; D013839:Thiamphenicol
keywords: Piscirickettsia salmonis; RND efflux pump; SRS; acrAB efflux pump; antibiotic resistance; florfenicol