Borrelia host adaptation Protein (BadP) is required for the colonization of a mammalian host by the agent of Lyme disease

Borrelia burgdorferi ( Bb ), the agent of Lyme disease (LD), uses host-derived signals to modulate gene expression during the vector and mammalian phases of infection. Microarray analysis of mutants lacking Borrelia host-adaptation Regulator (BadR) revealed down-regulation of genes encoding enzymes whose role in the patho-physiology of Bb is unknown. Immunoblot analysis of the badR mutants confirmed reduced levels of these enzymes and one of these enzymes encoded by bb0086 , shares homology to prokaryotic magnesium chelatase and Lon-type proteases. BB0086 levels were higher in Bb under conditions mimicking fed ticks. Mutants lacking bb0086 had no apparent in vitro growth defect but were incapable of colonizing immunocompetent C3H/HeN and immunodeficient SCID mice. Immunoblot analysis revealed reduced levels of proteins critical for adaptation of Bb to the mammalian host such as OspC, DbpA and BBK32. Both RpoS and BosR - key regulators of gene expression in Bb - were downregulated in the bb0086 mutants. Therefore, we designated BB0086 as Borrelia host-adaptation Protein (BadP). Unlike badP mutants, the control strains established infection in C3H/HeN mice at 4 days post infection, indicating an early colonization defect in mutants due to reduced levels of lipoproteins/regulators critical for initial stages of infection. However, badP mutants survived within dialysis membrane chambers (DMCs) implanted within rat peritoneal cavity but unlike the control strains did not display complete switching of OspA to OspC suggesting incomplete adaptation to mammalian phase of infection. These findings have opened a novel regulatory mechanism, which impacts the virulence potential of Bb .