title: The GBS PI-2a pilus is required for virulence in mice neonates.
abstract: BACKGROUND
  Streptococcus agalactiae (Group B Streptococcus) is a leading cause of sepsis and meningitis in newborns. Most bacterial pathogens, including gram-positive bacteria, have long filamentous structures known as pili extending from their surface. Although pili are described as adhesive organelles, they have been also implicated in many other functions including thwarting the host immune responses. We previously characterized the pilus-encoding operon PI-2a (gbs1479-1474) in strain NEM316. This pilus is composed of three structural subunit proteins: PilA (Gbs1478), PilB (Gbs1477), and PilC (Gbs1474), and its assembly involves two class C sortases (SrtC3 and SrtC4). PilB, the bona fide pilin, is the major component whereas PilA, the pilus associated adhesin, and PilC the pilus anchor are both accessory proteins incorporated into the pilus backbone.
  
  
  RESULTS
  In this study, the role of the major pilin subunit PilB was tested in systemic virulence using 6-weeks old and newborn mice. Notably, the non-piliated ΔpilB mutant was less virulent than its wild-type counterpart in the newborn mice model. Next, we investigated the possible role(s) of PilB in resistance to innate immune host defenses, i.e. resistance to macrophage killing and to antimicrobial peptides. Phagocytosis and survival of wild-type NEM316 and its isogenic ΔpilB mutant in immortalized RAW 264.7 murine macrophages were not significantly different whereas the isogenic ΔsodA mutant was more susceptible to killing. These results were confirmed using primary peritoneal macrophages. We also tested the activities of five cationic antimicrobial peptides (AMP-1D, LL-37, colistin, polymyxin B, and mCRAMP) and found no significant difference between WT and ΔpilB strains whereas the isogenic dltA mutant showed increased sensitivity.
  
  
  CONCLUSIONS
  These results question the previously described role of PilB pilus in resistance to the host immune defenses. Interestingly, PilB was found to be important for virulence in the neonatal context.
authors.affiliation: Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram-Positif, Paris, France.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Papasergi
authors.forename: Sara
authors.initials: S
authors.lastname: Brega
authors.forename: Michel-Yves
authors.initials: MY
authors.lastname: Mistou
authors.forename: Arnaud
authors.initials: A
authors.lastname: Firon
authors.forename: Virginie
authors.initials: V
authors.lastname: Oxaran
authors.forename: Ron
authors.initials: R
authors.lastname: Dover
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Teti
authors.forename: Yechiel
authors.initials: Y
authors.lastname: Shai
authors.forename: Patrick
authors.initials: P
authors.lastname: Trieu-Cuot
authors.forename: Shaynoor
authors.initials: S
authors.lastname: Dramsi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins / Q000378:metabolism*; D054804:Cathelicidins / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D010861:Fimbriae, Bacterial / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism*; D013290:Streptococcal Infections / Q000382:microbiology; D013292:Streptococcus agalactiae / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*; D014774:Virulence / Q000187:drug effects
chemical_list: D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D054804:Cathelicidins; D010088:Oxidoreductases; C068255:pilB protein, Bacteria