title: Host cell-derived lactate functions as an effector molecule in Neisseria meningitidis microcolony dispersal.
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.
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Sigurlásdóttir
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Jakob
authors.initials: J
authors.lastname: Engman
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Olaspers Sara
authors.initials: OS
authors.lastname: Eriksson
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Sunil D
authors.initials: SD
authors.lastname: Saroj
authors.affiliation: Department of Environmental Science and Analytical Chemistry, Stockholm University, Stockholm, Sweden.
authors.forename: Nadezda
authors.initials: N
authors.lastname: Zguna
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Pilar
authors.identifier: http://orcid.org/0000-0002-2487-9860
authors.initials: P
authors.lastname: Lloris-Garcerá
authors.affiliation: Department of Environmental Science and Analytical Chemistry, Stockholm University, Stockholm, Sweden.
authors.forename: Leopold L
authors.initials: LL
authors.lastname: Ilag
authors.affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Ann-Beth
authors.identifier: http://orcid.org/0000-0002-4480-2940
authors.initials: AB
authors.lastname: Jonsson
mesh_terms: D001422:Bacterial Adhesion / Q000502:physiology*; D001426:Bacterial Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000382:microbiology*; D010861:Fimbriae, Bacterial / Q000382:microbiology; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D008589:Meningococcal Infections / Q000378:metabolism*; D009344:Neisseria gonorrhoeae / Q000472:pathogenicity; D009345:Neisseria meningitidis / Q000472:pathogenicity*; D014774:Virulence / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D019344:Lactic Acid