The Listeria monocytogenes ChiA Chitinase Enhances Virulence through Suppression of Host Innate Immunity

ABSTRACT Environmental pathogens survive and replicate within the outside environment while maintaining the capacity to infect mammalian hosts. For somemicroorganisms, mammalian infectionmay 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 en-hances L. monocytogenes survival in vivo through the suppression of host innate immunity. L. monocytogenes chiAmutants were fully capable of establishing bacterial replication within target organs during the first 48 h of infection. By 72 to 96 h postin-fection, however, numbers ofchiA bacteria diminished, indicative of an effective immune response to contain infection. The chiA-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 dra-matic decrease in inducible nitric oxide synthase (iNOS) expression, andchiAmutant virulence was restored inNOS2/mice lacking iNOS. This work is the first to demonstrate modulation of a specific host innate immune response by a bacterial chiti-nase