title: Staphylococcus aureus but not Listeria monocytogenes adapt to triclosan and adaptation correlates with increased fabI expression and agr deficiency.
abstract: BACKGROUND
  The ability of pathogens to adapt to the widely used biocide, triclosan, varies substantially. The purpose of the study was to examine bacterial adaptation over an extended period of time to low increments of triclosan concentrations. Focus was two human pathogens, S. aureus and L. monocytogenes that previously have displayed inherent high and low adaptability, respectively.
  
  
  RESULTS
  Three strains of L. monocytogenes and two strains of S. aureus including the community-acquired USA300 were exposed to increasing, sub-lethal concentrations of triclosan in triclosan-containing agar gradients. Following 25 days of exposure on agar plates to sub-lethal concentrations of triclosan with a twofold concentration increase every second day, minimum inhibitory concentration (MIC) for S. aureus increased from 0.125 (8325-4) and 0.0625 (USA 300) mg/L to 4 mg/L. The MIC of all three L. monocytogenes strains was initially 4 mg/L and remained unaltered by the exposure. The adapted S. aureus isolates retained normal colony size but displayed increased expression of fabI encoding an essential enzyme in bacterial fatty acid synthesis. Also, they displayed decreased or no expression of the virulence associated agrC of the agr quorum sensing system. While most adapted strains of USA300 carried mutations in fabI, none of the adapted strains of 8325-4 did.
  
  
  CONCLUSIONS
  Adaptability to triclosan varies substantially between Gram positive human pathogens. S. aureus displayed an intrinsically lower MIC for triclosan compared to L. monocytogenes but was easily adapted leading to the same MIC as L. monocytogenes. Even though all adapted S. aureus strains over-expressed fabI and eliminated expression of the agr quorum sensing system, adaptation in USA300 involved fabI mutations whereas this was not the case for 8325-4. Thus, adaptation to triclosan by S. aureus appears to involve multiple genetic pathways.
authors.forename: Lene Nørby
authors.initials: LN
authors.lastname: Nielsen
authors.forename: Marianne Halberg
authors.initials: MH
authors.lastname: Larsen
authors.forename: Sissel
authors.initials: S
authors.lastname: Skovgaard
authors.forename: Vicky
authors.initials: V
authors.lastname: Kastbjerg
authors.forename: Henrik
authors.initials: H
authors.lastname: Westh
authors.forename: Lone
authors.initials: L
authors.lastname: Gram
authors.forename: Hanne
authors.initials: H
authors.lastname: Ingmer
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D054889:Fatty Acid Synthase, Type II / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D008089:Listeria monocytogenes / Q000187:drug effects* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D009154:Mutation; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014260:Triclosan / Q000494:pharmacology*
chemical_list: C095698:Agr protein, Staphylococcus aureus; D000891:Anti-Infective Agents, Local; D001426:Bacterial Proteins; D015534:Trans-Activators; D014260:Triclosan; D054889:Fatty Acid Synthase, Type II
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