Type IV pilus retraction enables sustained bacteremia and plays a key role in the outcome of meningococcal sepsis in a humanized mouse model

PLoS Pathog. 2021 Feb 16;17(2):e1009299. doi: 10.1371/journal.ppat.1009299. eCollection 2021 Feb.


Neisseria meningitidis (the meningococcus) remains a major cause of bacterial meningitis and fatal sepsis. This commensal bacterium of the human nasopharynx can cause invasive diseases when it leaves its niche and reaches the bloodstream. Blood-borne meningococci have the ability to adhere to human endothelial cells and rapidly colonize microvessels. This crucial step enables dissemination into tissues and promotes deregulated inflammation and coagulation, leading to extensive necrotic purpura in the most severe cases. Adhesion to blood vessels relies on type IV pili (TFP). These long filamentous structures are highly dynamic as they can rapidly elongate and retract by the antagonistic action of two ATPases, PilF and PilT. However, the consequences of TFP dynamics on the pathophysiology and the outcome of meningococcal sepsis in vivo have been poorly studied. Here, we show that human graft microvessels are replicative niches for meningococci, that seed the bloodstream and promote sustained bacteremia and lethality in a humanized mouse model. Intriguingly, although pilus-retraction deficient N. meningitidis strain (ΔpilT) efficiently colonizes human graft tissue, this mutant did not promote sustained bacteremia nor induce mouse lethality. This effect was not due to a decreased inflammatory response, nor defects in bacterial clearance by the innate immune system. Rather, TFP-retraction was necessary to promote the release of TFP-dependent contacts between bacteria and, in turn, the detachment from colonized microvessels. The resulting sustained bacteremia was directly correlated with lethality. Altogether, these results demonstrate that pilus retraction plays a key role in the occurrence and outcome of meningococcal sepsis by supporting sustained bacteremia. These findings open new perspectives on the role of circulating bacteria in the pathological alterations leading to lethal sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteremia / metabolism
  • Bacteremia / microbiology*
  • Bacteremia / pathology
  • Bacterial Adhesion
  • Disease Models, Animal*
  • Endothelial Cells
  • Female
  • Fimbriae Proteins / genetics
  • Fimbriae Proteins / metabolism*
  • Fimbriae, Bacterial / physiology*
  • Humans
  • Meningococcal Infections / metabolism
  • Meningococcal Infections / microbiology*
  • Meningococcal Infections / pathology
  • Mice
  • Mice, SCID
  • Neisseria meningitidis / pathogenicity*
  • Sepsis / metabolism
  • Sepsis / microbiology*
  • Sepsis / pathology
  • Skin Transplantation


  • Fimbriae Proteins

Grant support

This work was supported by Université de Paris, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Fondation pour la Recherche Médicale (FRM) and a grant from Agence nationale de la Recherche (ANR) RETRACTOPATH (ANR-18-CE15-0019-01 - grant recipient XN and SB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.