title: Neisseria gonorrhoeae metalloprotease NGO1686 is required for full piliation, and piliation is required for resistance to H2O2- and neutrophil-mediated killing.
abstract: The sexually transmitted infection gonorrhea is caused exclusively by the human-specific pathogen Neisseria gonorrhoeae. Type IV pili are an essential virulence factor uniformly expressed on clinical gonococcal isolates and are required for several aspects of gonococcal pathogenesis, including adherence to host tissues, autoagglutination, twitching motility, and the uptake of DNA during transformation. Symptomatic gonococcal infection is characterized by the influx of neutrophils or polymorphonuclear leukocytes (PMNs) to the site of infection. PMNs are a key component of gonococcal pathogenesis, mediating the innate immune response through the use of oxidative and nonoxidative killing mechanisms. The M23B family zinc metallopeptidase NGO1686 is required for gonococci to survive oxidative killing by H2O2- and PMN-mediated killing through unknown mechanisms, but the only known target of NGO1686 is peptidoglycan. We report that the effect of NGO1686 on survival after exposure to H2O2 and PMNs is mediated through its role in elaborating pili and that nonpiliated mutants of N. gonorrhoeae are less resistant to killing by H2O2, LL-37, and PMNs than the corresponding piliated strains. These findings add to the various virulence-associated functions attributable to gonococcal pili and may explain the selection basis for piliation in clinical isolates of N. gonorrhoeae.
  
  
  OBJECTIVE
  Successful infectious agents need to overcome host defense systems to establish infection. We show that the Neisseria pilus, a major virulence factor of this organism, which causes gonorrhea, helps protect the bacterium from two major killing mechanisms used by the host to combat infections. We also show that to express the pilus, an enzyme needs to partially degrade the cell wall of the bacterium.
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Stohl
authors.forename: Erin M
authors.initials: EM
authors.lastname: Dale
authors.forename: Alison K
authors.initials: AK
authors.lastname: Criss
authors.forename: H Steven
authors.initials: HS
authors.lastname: Seifert
mesh_terms: D010861:Fimbriae, Bacterial / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000633:toxicity*; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism*; D050296:Microbial Viability; D009344:Neisseria gonorrhoeae / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology*; D018384:Oxidative Stress; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D037521:Virulence Factors; D006861:Hydrogen Peroxide; D045726:Metalloproteases