Plasticity in early immune evasion strategies of a bacterial pathogen

Significance Borrelia burgdorferi is one of the few extracellular pathogens capable of establishing persistent infection. We show that a spirochete surface protein of unknown function, BBA57, is an unorthodox regulator of multiple virulent determinants. The protein orchestrates unique host immune evasion strategies crucial for early spirochete infection in mammals. It suppresses host complement-mediated killing and neutrophil-derived microbicidal responses, including induction of antimicrobial peptides, and promotes pathogen dissemination by regulating type I interferon. In the absence of BBA57, spirochetes can undergo nonheritable transcriptional reprograming events ultimately favoring pathogen persistence. These studies highlight the evolution of plasticity in immune evasion strategies of atypical pathogens likeB. burgdorferi , which is remarkably adapted to persist in multiple hosts and on a long-term basis without host clearance.