title: Modulation of Staphylococcus aureus Biofilm Matrix by Subinhibitory Concentrations of Clindamycin.
abstract: Staphylococcus aureus biofilms are extremely difficult to treat. They provide a protected niche for the bacteria, rendering them highly recalcitrant toward host defenses as well as antibiotic treatment. Bacteria within a biofilm are shielded from the immune system by the formation of an extracellular polymeric matrix, composed of polysaccharides, extracellular DNA (eDNA), and proteins. Many antibiotics do not readily penetrate biofilms, resulting in the presence of subinhibitory concentrations of antibiotics. Here, we show that subinhibitory concentrations of clindamycin triggered a transcriptional stress response in S. aureus via the alternative sigma factor B (σ(B)) and upregulated the expression of the major biofilm-associated genes atlA, lrgA, agrA, the psm genes, fnbA, and fnbB Our data suggest that subinhibitory concentrations of clindamycin alter the ability of S. aureus to form biofilms and shift the composition of the biofilm matrix toward higher eDNA content. An understanding of the molecular mechanisms underlying biofilm assembly and dispersal in response to subinhibitory concentrations of clinically relevant antibiotics such as clindamycin is critical to further optimize antibiotic treatment strategies of biofilm-associated S. aureus infections.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland katrin.schilcher@uzh.ch annelies.zinkernagel@usz.ch.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schilcher
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Federica
authors.initials: F
authors.lastname: Andreoni
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Vanina
authors.initials: V
authors.lastname: Dengler Haunreiter
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Kati
authors.identifier: 0000-0002-2484-6364
authors.initials: K
authors.lastname: Seidl
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Hasse
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland katrin.schilcher@uzh.ch annelies.zinkernagel@usz.ch.
authors.forename: Annelies S
authors.initials: AS
authors.lastname: Zinkernagel
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D002981:Clindamycin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000187:drug effects / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006801:Humans; D009154:Mutation; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D002981:Clindamycin