Increased neutrophil extracellular trap-mediated Staphylococcus aureus clearance through inhibition of nuclease activity by clindamycin and immunoglobulin.

2.50
Hdl Handle:
http://hdl.handle.net/10033/345681
Title:
Increased neutrophil extracellular trap-mediated Staphylococcus aureus clearance through inhibition of nuclease activity by clindamycin and immunoglobulin.
Authors:
Schilcher, Katrin; Andreoni, Federica; Uchiyama, Satoshi; Ogawa, Taiji; Schuepbach, Reto A; Zinkernagel, Annelies S
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.
Affiliation:
Helmholtz Centre for infection reseach, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Increased neutrophil extracellular trap-mediated Staphylococcus aureus clearance through inhibition of nuclease activity by clindamycin and immunoglobulin. 2014, 210 (3):473-82 J. Infect. Dis.
Journal:
The Journal of infectious diseases
Issue Date:
1-Aug-2014
URI:
http://hdl.handle.net/10033/345681
DOI:
10.1093/infdis/jiu091
PubMed ID:
24526740
Type:
Article
Language:
en
ISSN:
1537-6613
Appears in Collections:
Publications of Dept. Medizinische Mikrobiologie (MMIK)

Full metadata record

DC FieldValue Language
dc.contributor.authorSchilcher, Katrinen
dc.contributor.authorAndreoni, Federicaen
dc.contributor.authorUchiyama, Satoshien
dc.contributor.authorOgawa, Taijien
dc.contributor.authorSchuepbach, Reto Aen
dc.contributor.authorZinkernagel, Annelies Sen
dc.date.accessioned2015-02-27T15:05:55Zen
dc.date.available2015-02-27T15:05:55Zen
dc.date.issued2014-08-01en
dc.identifier.citationIncreased neutrophil extracellular trap-mediated Staphylococcus aureus clearance through inhibition of nuclease activity by clindamycin and immunoglobulin. 2014, 210 (3):473-82 J. Infect. Dis.en
dc.identifier.issn1537-6613en
dc.identifier.pmid24526740en
dc.identifier.doi10.1093/infdis/jiu091en
dc.identifier.urihttp://hdl.handle.net/10033/345681en
dc.description.abstractThe 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.en
dc.language.isoenen
dc.subject.meshClindamycinen
dc.subject.meshDose-Response Relationship, Drugen
dc.subject.meshGene Expression Regulation, Bacterialen
dc.subject.meshGene Expression Regulation, Enzymologicen
dc.subject.meshHumansen
dc.subject.meshImmunoglobulinsen
dc.subject.meshStaphylococcus aureusen
dc.titleIncreased neutrophil extracellular trap-mediated Staphylococcus aureus clearance through inhibition of nuclease activity by clindamycin and immunoglobulin.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection reseach, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalThe Journal of infectious diseasesen

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