Host cell-derived lactate functions as an effector molecule in Neisseria meningitidis microcolony dispersal

PLoS Pathog. 2017 Apr 6;13(4):e1006251. doi: 10.1371/journal.ppat.1006251. eCollection 2017 Apr.

Abstract

The development of meningococcal disease, caused by the human pathogen Neisseria meningitidis, is preceded by the colonization of the epithelial layer in the nasopharynx. After initial adhesion to host cells meningococci form aggregates, through pilus-pilus interactions, termed microcolonies from which the bacteria later detach. Dispersal from microcolonies enables access to new colonization sites and facilitates the crossing of the cell barrier; however, this process is poorly understood. In this study, we used live-cell imaging to investigate the process of N. meningitidis microcolony dispersal. We show that direct contact with host cells is not required for microcolony dispersal, instead accumulation of a host-derived effector molecule induces microcolony dispersal. By using a host-cell free approach, we demonstrated that lactate, secreted from host cells, initiate rapid dispersal of microcolonies. Interestingly, metabolic utilization of lactate by the bacteria was not required for induction of dispersal, suggesting that lactate plays a role as a signaling molecule. Furthermore, Neisseria gonorrhoeae microcolony dispersal could also be induced by lactate. These findings reveal a role of host-secreted lactate in microcolony dispersal and virulence of pathogenic Neisseria.

MeSH terms

  • Bacterial Adhesion / physiology*
  • Bacterial Proteins / metabolism*
  • Epithelial Cells / microbiology*
  • Fimbriae, Bacterial / microbiology
  • Humans
  • Lactic Acid / metabolism*
  • Meningococcal Infections / metabolism*
  • Neisseria gonorrhoeae / pathogenicity
  • Neisseria meningitidis / pathogenicity*
  • Virulence / physiology

Substances

  • Bacterial Proteins
  • Lactic Acid

Grants and funding

This work was supported by the Swedish Research Council (http://www.vr.se) (Dnr 2006-4112, 2012-2415, 2013-2434), The Swedish Cancer Society (https://www.cancerfonden.se) and Torsten Söderbergs Stiftelse (http://www.torstensoderbergsstiftelse.se) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.