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

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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.

No MeSH data available.


Environmental concentration of lactate influences microcolony dispersal in pathogenic Neisseria.Proposed model of lactate-induced microcolony dispersal in pathogenic Neisseria. (A) In presence of high lactate concentration the microcolony dispersal of pathogenic Neisseria is rapid regardless of whether microcolonies are in direct contact with host cells or not. (B) In low lactate concentrations, pathogenic Neisseria remain in microcolonies.
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ppat.1006251.g009: Environmental concentration of lactate influences microcolony dispersal in pathogenic Neisseria.Proposed model of lactate-induced microcolony dispersal in pathogenic Neisseria. (A) In presence of high lactate concentration the microcolony dispersal of pathogenic Neisseria is rapid regardless of whether microcolonies are in direct contact with host cells or not. (B) In low lactate concentrations, pathogenic Neisseria remain in microcolonies.

Mentions: 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.


Host cell-derived lactate functions as an effector molecule in Neisseria meningitidis microcolony dispersal
Environmental concentration of lactate influences microcolony dispersal in pathogenic Neisseria.Proposed model of lactate-induced microcolony dispersal in pathogenic Neisseria. (A) In presence of high lactate concentration the microcolony dispersal of pathogenic Neisseria is rapid regardless of whether microcolonies are in direct contact with host cells or not. (B) In low lactate concentrations, pathogenic Neisseria remain in microcolonies.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5383330&req=5

ppat.1006251.g009: Environmental concentration of lactate influences microcolony dispersal in pathogenic Neisseria.Proposed model of lactate-induced microcolony dispersal in pathogenic Neisseria. (A) In presence of high lactate concentration the microcolony dispersal of pathogenic Neisseria is rapid regardless of whether microcolonies are in direct contact with host cells or not. (B) In low lactate concentrations, pathogenic Neisseria remain in microcolonies.
Mentions: 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.

View Article: PubMed Central - PubMed

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.

No MeSH data available.