Pathogens possess the ability to adapt and survive in some host species but not in others-an ecological trait known as host tropism. Transmitted through ticks and carried mainly by mammals and birds, the Lyme disease (LD) bacterium is a well-suited model to study such tropism. Three main causative agents of LD, Borrelia burgdorferi, B. afzelii, and B. garinii, vary in host ranges through mechanisms eluding characterization. By feeding ticks infected with different Borrelia species, utilizing feeding chambers and live mice and quail, we found species-level differences in bacterial transmission. These differences localize on the tick blood meal, and specifically complement, a defense in vertebrate blood, and a polymorphic bacterial protein, CspA, which inactivates complement by binding to a host complement inhibitor, Factor H (FH). CspA selectively confers bacterial transmission to vertebrates that produce FH capable of allele-specific recognition. CspA is the only member of the Pfam54 gene family to exhibit host-specific FH-binding. Phylogenetic analyses revealed convergent evolution as the driver of such uniqueness, and that FH-binding likely emerged during the last glacial maximum. Our results identify a determinant of host tropism in Lyme disease infection, thus defining an evolutionary mechanism that shapes host-pathogen associations.

Department of Biological Sciences State University of New York at Albany Albany New York United States of America

Department of Biomedical Sciences State University of New York at Albany Albany New York United States of America

Department of Ecology Evolution and Environmental Biology Columbia University New York New York United States of America

Department of Epidemiology and Biostatistics School of Public Health SUNY Downstate Health Sciences University Brooklyn New York United States of America

Division of Infectious Diseases and Immunology University of Massachusetts Medical School Worcester Massachusetts United States of America

Division of Infectious Diseases Department of Medicine College of Medicine SUNY Downstate Health Sciences University Brooklyn New York United States of America

Division of Infectious Diseases Wadsworth Center New York State Department of Health Albany New York United States of America

Division of Medical Protein Chemistry Department of Translational Medicine Lund University Malmo Sweden

Faculty of Science University of South Bohemia České Budějovice Czech Republic

Institute for Genomic Health SUNY Downstate Health Sciences University Brooklyn New York United States of America

Institute of Medical Microbiology and Infection Control University Hospital of Frankfurt Goethe University Frankfurt Frankfurt Germany

Institute of Parasitology Czech Academy of Sciences České Budějovice Czech Republic

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Tailored Functionalization of Plasmonic AgNPs/C:H:N:O Nanocomposite for Sensitive and Selective Detection

Natural selection and recombination at host-interacting lipoprotein loci drive genome diversification of Lyme disease and related bacteria