Staphylococcus aureus small colony variants are resistant to the antimicrobial peptide lactoferricin B

Objectives: 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 pept...

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Veröffentlicht in:Journal of antimicrobial chemotherapy 2005-12, Vol.56 (6), p.1126-1129
Hauptverfasser: Samuelsen, Ørjan, Haukland, Hanne Husom, Kahl, Barbara C., von Eiff, Christof, Proctor, Richard A., Ulvatne, Hilde, Sandvik, Kjersti, Vorland, Lars H.
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container_end_page 1129
container_issue 6
container_start_page 1126
container_title Journal of antimicrobial chemotherapy
container_volume 56
creator Samuelsen, Ørjan
Haukland, Hanne Husom
Kahl, Barbara C.
von Eiff, Christof
Proctor, Richard A.
Ulvatne, Hilde
Sandvik, Kjersti
Vorland, Lars H.
description Objectives: 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.
doi_str_mv 10.1093/jac/dki385
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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 &gt;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.</description><identifier>ISSN: 0305-7453</identifier><identifier>EISSN: 1460-2091</identifier><identifier>DOI: 10.1093/jac/dki385</identifier><identifier>PMID: 16287983</identifier><identifier>CODEN: JACHDX</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Anti-Bacterial Agents - metabolism ; Anti-Bacterial Agents - pharmacology ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; antimicrobial resistance ; Biological and medical sciences ; cellular uptake ; Cytoplasm - chemistry ; Drug Resistance, Bacterial ; electron microscopy ; Hemin - genetics ; immunolabelling ; Lactoferrin - metabolism ; Lactoferrin - pharmacology ; Medical sciences ; Membrane Potentials ; metabolic resistance ; Microbial Sensitivity Tests ; Microscopy, Electron, Transmission ; Microscopy, Immunoelectron ; Mutation ; Pharmacology. 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Antimicrob. Chemother</addtitle><description>Objectives: 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 &gt;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.</description><subject>Anti-Bacterial Agents - metabolism</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antibiotics. Antiinfectious agents. 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Antimicrob. Chemother</addtitle><date>2005-12-01</date><risdate>2005</risdate><volume>56</volume><issue>6</issue><spage>1126</spage><epage>1129</epage><pages>1126-1129</pages><issn>0305-7453</issn><eissn>1460-2091</eissn><coden>JACHDX</coden><abstract>Objectives: 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 &gt;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.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>16287983</pmid><doi>10.1093/jac/dki385</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record>
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subjects Anti-Bacterial Agents - metabolism
Anti-Bacterial Agents - pharmacology
Antibiotics. Antiinfectious agents. Antiparasitic agents
antimicrobial resistance
Biological and medical sciences
cellular uptake
Cytoplasm - chemistry
Drug Resistance, Bacterial
electron microscopy
Hemin - genetics
immunolabelling
Lactoferrin - metabolism
Lactoferrin - pharmacology
Medical sciences
Membrane Potentials
metabolic resistance
Microbial Sensitivity Tests
Microscopy, Electron, Transmission
Microscopy, Immunoelectron
Mutation
Pharmacology. Drug treatments
resistance mechanism
Staphylococcus aureus
Staphylococcus aureus - drug effects
Staphylococcus aureus - genetics
Staphylococcus aureus - growth & development
Thymidine - genetics
transmembrane potential
Vitamin K 3 - metabolism
title Staphylococcus aureus small colony variants are resistant to the antimicrobial peptide lactoferricin B
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