Neisseria meningitidis is a major cause of human bacterial meningitis and sepsis worldwide. The bacteria are known to aggregate into microcolonies in epithelial cells in the throat, before dispersal may facilitate the establishment of invasive disease.
In a new study, Ann-Beth Jonsson and colleagues at Stockholm University found that host cell-derived lactate induces N. meningitides microcolony dispersal and may act as a signaling molecule. I interviewed Jonsson via email to learn more about her findings and their implications for disease progression.
What drew you to the study of N. meningitidis infection, and what do you like about this field?
AJ: My interest in microbes and especially bacteria started in high school when I realized how abundant and essential they are. The interaction between bacteria and host cells is especially fascinating: N. meningitidis infection may have a rapid and fatal outcome, but these bacteria may also coexist with us asymptomatically in the throat.
What are N. meningitidis microcolonies, and why is their dispersal important in infection?
AJ: Microcolonies are community-based structures that N. meningitidis form. The structures may protect bacteria against fluid forces in the human throat. Bacterial dispersal from these microcolonies is necessary for entry into human cells and further spread in the body.
Most people have only heard of lactate as a waste product, created when we exercise and responsible for muscle soreness. In your study, you found that this small organic compound induces rapid N. meningitidis microcolony dispersal. How did you discover this, and did the finding surprise you?
AJ: Initially we found that human cells release a substance that N. meningitidis respond to by detaching from the microcolonies. Through further research, we were able to exclude large groups of compounds, which directed us towards small metabolites. When we identified lactate, the most surprising thing was that such a common metabolite could determine and drive bacterial behavior.
What do you know about the pathway by which host-derived lactate exerts this effect on N. meningitidis?
AJ: Whilst N. meningitidis can metabolize lactate, we know that lactate-induced dispersal is not dependent on this metabolic utilization. Instead, the data suggest that the lactate molecule acts as a signal which is sensed by the bacteria.
What might be the evolutionary advantage of lactate being the trigger for N. meningitidis microcolony dispersal?
AJ: It may be useful for N. meningitidis to “read” the host by sensing a host-derived signal. As the bacteria grow faster in the presence of lactate, the molecule may signal the presence of nutrition. Lactate could also act as a host danger signal since its level is high during infection.
What impact do you hope your study might have, and what are the next steps for your research?
AJ: The next step will be to identify the mechanistic details of how host-secreted metabolites serve as signaling molecules in bacterial pathogenesis. Understanding how lactate acts to induce bacterial dispersal might aid development of a tool to block passage of N. meningitidis into the human bloodstream. Eventually, understanding the molecular mechanisms of N. meningitidis infection could help to find new ways to prevent and treat life-threatening meningococcal disease.
Research Article: Sigurlásdóttir S, Engman J, Eriksson OS, Saroj SD, Zguna N, Lloris-Garcerá P, et al. (2017) Host cell-derived lactate functions as an effector molecule in Neisseria meningitidis microcolony dispersal. PLoS Pathog 13(4): e1006251. doi:10.1371/journal.ppat.1006251
Images Credits: Sigurlásdóttir et al., 2017; Jonsson and Sigurlásdóttir, 2017