title: A thermonuclease of Neisseria gonorrhoeae enhances bacterial escape from killing by neutrophil extracellular traps.
abstract: Acute gonorrhea is characterized by neutrophilic inflammation that is insufficient to clear Neisseria gonorrhoeae. Activated neutrophils release extracellular traps (NETs), which are composed of chromatin and decorated with antimicrobial proteins. The N. gonorrhoeae NG0969 open reading frame contains a gene (nuc) that encodes a putatively secreted thermonuclease (Nuc) that contributes to biofilm remodeling. Here, we report that Nuc degrades NETs to help N. gonorrhoeae resist killing by neutrophils. Primary human neutrophils released NETs after exposure to N. gonorrhoeae, but NET integrity declined over time with Nuc-containing bacteria. Recombinant Nuc and conditioned medium from Nuc-containing N. gonorrhoeae degraded human neutrophil DNA and NETs. NETs were found to have antimicrobial activity against N. gonorrhoeae, and Nuc expression enhanced N. gonorrhoeae survival in the presence of neutrophils that released NETs. We propose that Nuc enables N. gonorrhoeae to escape trapping and killing by NETs during symptomatic infection, highlighting Nuc as a multifunctional virulence factor for N. gonorrhoeae.
authors.affiliation: Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Juneau
authors.affiliation: Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville.
authors.forename: Jacqueline S
authors.initials: JS
authors.lastname: Stevens
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Apicella
authors.affiliation: Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville.
authors.forename: Alison K
authors.initials: AK
authors.lastname: Criss
mesh_terms: D001426:Bacterial Proteins / Q000502:physiology*; D002478:Cells, Cultured; D065206:Extracellular Traps / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D050296:Microbial Viability; D008836:Micrococcal Nuclease / Q000502:physiology*; D009344:Neisseria gonorrhoeae / Q000201:enzymology* / Q000276:immunology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology
chemical_list: D001426:Bacterial Proteins; D008836:Micrococcal Nuclease
keywords: Neisseria gonorrhoeae; Nuc; neutrophil; neutrophil extracellular traps; polymorphonuclear leukocyte; thermonuclease