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

• DOI: 10.1128/mbio.00617-12
• Publication Date: 2013-03-24T13:08:39Z
• Authors: Swarnava Chaudhuri; Benjamin N. Gantner; Richard D. Ye; Nicholas P. Cianc...; Nancy E. Freitag
• Keywords: Chitinase; Listeria infection

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