Environmental pathogens survive and replicate within the outside environment while maintaining the capacity to infect mammalian hosts. For some microorganisms, mammalian
infection may be a relatively rare event. Understanding how environmental pathogens retain their ability to cause disease may provide insight into environmental reservoirs of disease and emerging
infections. Listeria monocytogenes survives as a saprophyte in soil but is capable of causing serious invasive disease in susceptible individuals. The bacterium secretes
virulence factors that promote cell invasion, bacterial replication, and cell-to-cell spread. Recently, an L. monocytogenes
chitinase (ChiA) was shown to enhance
bacterial infection in mice. Given that mammals do not synthesize
chitin, the function of ChiA within infected animals was not clear. Here we have demonstrated that ChiA enhances L. monocytogenes survival in vivo through the suppression of host innate immunity. L. monocytogenes ΔchiA mutants were fully capable of establishing bacterial replication within target organs during the first 48 h of
infection. By 72 to 96 h postinfection, however, numbers of ΔchiA bacteria diminished, indicative of an effective immune response to contain
infection. The ΔchiA-associated virulence defect could be complemented in trans by wild-type L. monocytogenes, suggesting that secreted ChiA altered a target that resulted in a more permissive host environment for bacterial replication. ChiA secretion resulted in a dramatic decrease in
inducible nitric oxide synthase (iNOS) expression, and ΔchiA mutant virulence was restored in NOS2(-/-) mice lacking iNOS. This work is the first to demonstrate modulation of a specific host innate immune response by a bacterial
chitinase.
IMPORTANCE: Bacterial
chitinases have traditionally been viewed as
enzymes that either hydrolyze
chitin as a food source or serve as a defense mechanism against organisms containing structural
chitin (such as fungi). Recent evidence indicates that bacterial
chitinases and
chitin-
binding proteins contribute to pathogenesis, primarily via bacterial adherence to
chitin-like molecules present on the surface of mammalian cells. In contrast, mammalian
chitinases have been linked to immunity via inflammatory immune responses that occur outside the context of
infection, and since mammals do not produce
chitin, the targets of these mammalian
chitinases have remained elusive. This work demonstrates that a Listeria monocytogenes-secreted
chitinase has distinct functional roles that include
chitin hydrolysis and suppression of host innate immunity. The established link between
chitinase and the inhibition of host
inducible nitric oxide synthase (iNOS) expression may help clarify the thus far elusive relationship observed between mammalian
chitinase enzymes and host inflammatory responses occurring in the absence of
infection.