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

Date Published: April 6, 2017

Publisher: Public Library of Science

Author(s): Sara Sigurlásdóttir, Jakob Engman, Olaspers Sara Eriksson, Sunil D. Saroj, Nadezda Zguna, Pilar Lloris-Garcerá, Leopold L. Ilag, Ann-Beth Jonsson, Christoph Tang.


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.

Partial Text

Humans serve as the sole reservoir for the pathogen Neisseria meningitidis. The bacteria asymptomatically colonize the upper respiratory tract, with a prevalence of carriage ranging from 10 to 35% [1]. However, meningococci occasionally cross the epithelial mucosa and blood-brain barrier, causing life-threatening septicemia and meningitis [2]. Meningococcal adhesion to the epithelium in the nasopharynx is a prerequisite for colonization and pathogenicity [3], and this process can be divided into two steps. The initial interaction with cells is characterized by proliferation and adhesion as aggregates, called microcolonies. This stage is followed by the detachment of individual bacteria from the microcolonies, enabling relocation to new colonization sites or intimate adhesion to the cells in a single bacterial layer. Dispersal from microcolonies enables the meningococci to invade the mucosa and enter the circulation [4, 5].

The transition from nasopharyngeal colonization to an invasive infection is a crucial step in meningococcal pathogenicity. The detachment of meningococci from microcolonies allows bacteria to colonize new sites and to act as single cells that can cross the epithelial barrier [5, 14]. In this study, we investigated the importance of epithelial cells and cell-derived factors for microcolony dispersal. We demonstrated that the previously observed short and synchronized dispersal of microcolonies [41] requires the presence of live epithelial cells but not direct contact between cells and bacteria. Microcolony dispersal could be induced by a low-molecular weight host cell-derived factor that accumulated in cell-conditioned medium (i.e., CM) in absence of infectious agent. Furthermore, we showed that lactate is the active inducer of rapid microcolony dispersal in both N. meningitidis and N. gonorrhoeae. We propose that the microcolony dispersal in pathogenic Neisseria is influenced by environmental concentrations of lactate (Fig 9). Our data reveal a potential role of lactate as an effector molecule in colonization of pathogenic Neisseria.




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