title: Staphylococcus aureus small colony variants are resistant to the antimicrobial peptide lactoferricin B.
abstract: OBJECTIVE
  To determine whether Staphylococcus aureus small colony variants (SCVs) are resistant to the antimicrobial peptide lactoferricin B. To assess if deficiency in transmembrane potential, a common characteristic of SCVs that are haemin- or menadione-auxotrophs, affects the uptake of the peptide into the bacterial cytoplasm.
  
  
  METHODS
  A broth microdilution technique was used for susceptibility testing to determine the MIC of lactoferricin B for SCVs with three different auxotrophisms (haemin, menadione or thymidine) and their isogenic parent strains. Both clinical isolates and genetically defined mutants were used. The internalization of lactoferricin B in a hemB mutant and the respective parent strain was studied using transmission electron microscopy and immunogold labelling.
  
  
  RESULTS
  All SCVs showed reduced susceptibility to lactoferricin B irrespective of their auxotrophy compared with their isogenic parent strains. The MIC for all SCVs was >256 mg/L, whereas the MICs for the parent strains ranged from 16-256 mg/L. Surprisingly, the hemB mutant contained significantly more lactoferricin B intracellularly than the respective parent strain.
  
  
  CONCLUSIONS
  The resistance mechanism of SCVs towards the antimicrobial peptide lactoferricin B is presumably caused by the metabolic changes present in SCVs rather than by a changed transmembrane potential of SCVs or reduced uptake of the peptide.
authors.affiliation: Department of Medical Microbiology, University Hospital of North Norway, Tromsø, Norway. orjan.samuelsen@unn.no
authors.forename: Orjan
authors.initials: O
authors.lastname: Samuelsen
authors.forename: Hanne Husom
authors.initials: HH
authors.lastname: Haukland
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Kahl
authors.forename: Christof
authors.initials: C
authors.lastname: von Eiff
authors.forename: Richard A
authors.initials: RA
authors.lastname: Proctor
authors.forename: Hilde
authors.initials: H
authors.lastname: Ulvatne
authors.forename: Kjersti
authors.initials: K
authors.lastname: Sandvik
authors.forename: Lars H
authors.initials: LH
authors.lastname: Vorland
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D003593:Cytoplasm / Q000737:chemistry; D024881:Drug Resistance, Bacterial; D006427:Hemin / Q000235:genetics; D007781:Lactoferrin / Q000378:metabolism / Q000494:pharmacology*; D008564:Membrane Potentials; D008826:Microbial Sensitivity Tests; D046529:Microscopy, Electron, Transmission; D016253:Microscopy, Immunoelectron; D009154:Mutation; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D013936:Thymidine / Q000235:genetics; D024483:Vitamin K 3 / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; C082171:lactoferricin B; D024483:Vitamin K 3; D006427:Hemin; D007781:Lactoferrin; D013936:Thymidine