Borrelia nutrient acquisition throughout the enzootic cycle

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

The causative agent of Lyme disease (e.g., B. burgdorferi in the United States) is a spirochetal bacterium which transits between the hard tick vector, Ixodes spp., and mammalian hosts. The bacterial lifecycle is maintained between its tick vector and permissive reservoir species (i.e, the white-footed mouse, Peromyscus leucopus). B. burgdorferi does not undergo transovarial transmission to tick larvae, thus requiring an infected reservoir species to propagate the spirochete to uninfected ticks. The spirochete disseminates to nearly all tissues after a transient blood-borne phase and can persist at low densities for years. After ingesting an infected bloodmeal, ticks are colonized by the bacteria, then, after molting, can infect new reservoir populations, or incidentally infect humans. Unlike reservoir species, which display little to no effects of spirochete infection, humans mount a significant immune response against B. burgdorferi, resulting in the symptoms which are collectively known as Lyme disease. The causative agent of relapsing fever (e.g., B. hermsii in the United States) is morphologically and genomically similar to the Lyme disease Borrelia. However, the spirochete is generally transmitted by a soft tick vector, (e.g., Ornithodoros hermsi). The spirochete is also maintained in small mammal reservoirs, however the bacteria reside within the blood compartment and can reach high densities. The relapsing fever species do undergo transovarial transmission and its interaction with the soft tick vector is different than Lyme disease spirochetes and the hard tick vector. The transition of the spirochete between the tick vector and mammalian host depends on a complex regulatory network which coordinates nutritional acquisition programs, changes in the bacteria’s surface proteins, and cell motility. Changes in these systems allow permissible host-pathogen interfaces unique to either the tick or the mammal and each is essential for the bacterium’s survival. Nutrient acquisition is of particular import, as the Borrelia species are extreme auxotrophs, unable to generate many essential nutrients thus requiring exploitation of the host/vector environments for survival. Previous studies demonstrated the essential nature of peptide uptake for B. burgdorferi infection and viability. The system by which the spirochete acquires peptides, oligopeptide transport system (Opp), is a multicomponent transporter with peptide binding proteins (OppAs) which are structurally different and differentially expressed during the enzootic cycle. The Bacterial Physiology and Metabolism Unit focuses on understanding how this system meets the amino acid needs of the spirochete in vector/host microenvironments.