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dc.contributor.authorKaldestad, Marte Albriktseneng
dc.contributor.authorHaugland, Gyri Teieneng
dc.contributor.authorRønneseth, Anitaeng
dc.contributor.authorWergeland, Heidrun Ingereng
dc.contributor.authorSamuelsen, Ole Benteng
dc.description.abstractThe granuloma disease caused by Francisella noatunensis subsp. noatunensis in farmed Atlantic cod has not been successfully treated by use of antibacterials, even when antibacterial resistance testing indicates a sufficient effect. The reason for this treatment failure may be the intracellular existence of the bacteria within immune cells, mainly macrophages. To investigate the effect of antibacterials on intracellular Francisella replication, we established a protocol for the detection of drugs within Atlantic cod immune cells using high-performance liquid chromatography (HPLC). When the uptake and intracellular concentrations of oxolinic acid and flumequine were analysed in isolated adherent head kidney leucocytes (HKLs) by HPLC, we found that uptake was rapid and the intracellular concentrations reflected the extracellular exposure concentrations. To investigate the effect of the antibacterial compounds on intracellular bacterial replication, adherent HKLs experimentally infected with the bacteria were analysed using flow cytometry and intracellular labelling of bacteria by specific antibodies. We found that flumequine did not inhibit intracellular bacterial replication. Unexpectedly, the results indicated that the intracellularly effiacy of the drug was reduced. The HPLC method used proved to be highly applicable for accurate de - termination of intracellular drug concentrations. When combined with sensitive and specific flow cytometry analyses for identification and measurement of intracellular bacterial replication, we suggest that this approach can be very valuable for the design of antibacterial treatments of intracellular pathogens.en_US
dc.rightsAttribution CC BYeng
dc.subjectFrancisella noatunensis subsp. noatunensiseng
dc.subjectintracellular replicationeng
dc.subjectFlow cytometryeng
dc.subjectAtlantic codeng
dc.subjectGadus morhuaeng
dc.titleAntibiotic uptake by cultured Atlantic cod leucocytes and effect on intracellular Francisella noatunensis subsp. noatunensis replicationen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright The Authors 2014en_US
dc.source.journalDiseases of Aquatic Organisms

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