Borrelia burgdorferi nutrient acquisition throughout the enzootic cycle

National Institute Of Allergy And Infectious Diseases

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Abstract

Lyme disease is now recognized as the most prevalent vector-borne disease in the United States. Approximately 30,000 cases are reported to the CDC yearly, though incidences are thought to be as high as 300,000. Even with conventional treatment, a substantial proportion (10-20%) of patients remain symptomatic (Post-Treatment Lyme Disease Syndrome, PTLDS), resulting in a long-term reduction in quality of life. While the cause(s) of these recalcitrant symptoms are unknown, LD researchers conjecture that persister formation, outer membrane vesicle shedding, biofilm formation, viable but non-culturable organisms, and even pathogen-based immunomodulation could be pieces of this puzzle. The causative agent of Lyme disease, Borrelia burgdorferi, 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. 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 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 B. burgdorferi is unable to generate its own nutrients and requires 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.