The pathogenic Gram-positive bacterium Listeria monocytogenes causes severe acute infection in immunocompromised people including the very young and the very old. L. monocytogenes is the third most common cause of bacterial meningitis in neonates and causes abortion and stillbirth. Outbreaks of listeriosis continue to occur sporadically, recently claiming 20 lives in Canada. Whereas acute listeriosis is well-modeled in animals, chronic infection is more difficult to study and is consequently poorly understood. Bone marrow has been shown to harbor L. monocytogenes, suggesting that bone might be an important chronic reservoir from which the pathogen can infect the central nervous system. However, this infection is difficult to study because it involves only a few bacteria and the extent of infection cannot be assessed until after the animal is sacrificed.

Here, the authors use live animal imaging to examine bone marrow infection by L. monocytogenes. As in previous imaging studies of this pathogen in the gallbladder, they found that bone marrow is another site of chronic infection. In vivo bioluminescence demonstrated that bone marrow infection by this bacterium is focal, and that the foci appear after both oral and intravenous infection. Furthermore, although L. monocytogenes is hypothesized to be an obligate intracellular pathogen, highly attenuated mutants that are defective in intracellular replication can colonize the bone marrow, focally, for many weeks. Persistence of L. monocytogenes in this compartment supports the idea that the bone marrow is a niche for this, and perhaps other, pathogens.

Listeriosis can be very difficult to treat, sometimes requiring intravenous antibiotics for weeks. Studies of persistent bacterial infection should consider the bone marrow as a possible site of residual infection during, and after, treatment. In addition, this study demonstrates that the growth mechanism of attenuated L. monocytogenes is unclear; this is significant because attenuated strains are now in clinical trials to induce immune responses and eradicate established tumors without causing disease. The presence of L. monocytogenes in bone marrow might facilitate the induction of such immunity or, conversely, such persistence may indicate a lack of immune response and the induction of tolerance. Thus, in order to maximize efficacy and to ensure the safety of this treatment, future experiments should address immune stimulation in the bone marrow because this substantially sized niche might be beneficial, or detrimental, to anti-cancer therapy and other efforts.

2009