Leptospirosis is a widespread zoonotic and neglected
infectious disease of
human and
veterinary concern that is caused by pathogenic
Leptospira species. After entrance in the host, pathogenic leptospires evade the host natural
defense mechanisms in order to propagate and disseminate to multiple organs.
Myeloperoxidase is an
enzyme stored in
neutrophils azurophilic granules, and is released upon
neutrophil activation to produce mainly
hypochlorous acid, a strong
oxidant and potent
antimicrobial agent. In the present investigation, we studied the modulation of
myeloperoxidase activity by L. interrogans
serovar Copenhageni. We show that leptospires and their
culture supernatants are able to inhibit both
peroxidase and
chlorination activities of
myeloperoxidase, without interfering with
neutrophil degranulation. By leptospiral outer
membrane protein extraction and fractionation, we identified the
proteins LipL21 and LipL45 as
myeloperoxidase inhibitors, constituting new
Leptospira virulence factors. Accordingly, we propose a function for the
protein LipL21, one of the most expressed leptospiral outer
membrane proteins. Our results show a novel innate
immune evasion mechanism by which leptospires interfere with the host response in order to cope with the host
oxidative stress and efficiently achieve dissemination and colonization.