title: Increased neutrophil extracellular trap-mediated Staphylococcus aureus clearance through inhibition of nuclease activity by clindamycin and immunoglobulin.
abstract: The Gram-positive human pathogen Staphylococcus aureus causes a variety of human diseases such as skin infections, pneumonia, and endocarditis. The micrococcal nuclease Nuc1 is one of the major S. aureus virulence factors and allows the bacterium to avoid neutrophil extracellular trap (NET)-mediated killing. We found that addition of the protein synthesis inhibitor clindamycin to S. aureus LAC cultures decreased nuc1 transcription and subsequently blunted nuclease activity in a molecular beacon-based fluorescence assay. We also observed reduced NET degradation through Nuc1 inhibition translating into increased NET-mediated clearance. Similarly, pooled human immunoglobulin specifically inhibited nuclease activity in a concentration-dependent manner. Inhibition of nuclease activity by clindamycin and immunoglobulin enhanced S. aureus clearance and should be considered in the treatment of S. aureus infections.
authors: Division of Infectious Diseases and Hospital Epidemiology.
authors: Katrin
authors: K
authors: Schilcher
authors: Division of Infectious Diseases and Hospital Epidemiology.
authors: Federica
authors: F
authors: Andreoni
authors: Division of Infectious Diseases and Hospital Epidemiology.
authors: Satoshi
authors: S
authors: Uchiyama
authors: Division of Infectious Diseases and Hospital Epidemiology.
authors: Taiji
authors: T
authors: Ogawa
authors: Division of Surgical Intensive Care Medicine, University Hospital Zurich, University of Zurich, Switzerland.
authors: Reto A
authors: RA
authors: Schuepbach
authors: Division of Infectious Diseases and Hospital Epidemiology.
authors: Annelies S
authors: AS
authors: Zinkernagel
mesh_terms: D002981:Clindamycin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007136:Immunoglobulins / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D007136:Immunoglobulins; D002981:Clindamycin
keywords: NET; Staphylococcus aureus; clindamycin; immunoglobulin; molecular beacon; nuclease