Structural and Biomolecular Analyses of Borrelia burgdorferi BmpD Reveal a Substrate-Binding Protein of an ABC-Type Nucleoside Transporter Family

Julia Cuellar,Arto Liljeblad,Tiina A Salminen,Mia Åstrand,Heli Elovaara,Annukka Pietikäinen,Jukka Hytönen,Gabriela Guédez,Saija Sirén,Guy H Palmer

doi:10.1128/iai.00962-19

Julia Cuellar, Arto Liljeblad + Show 8 more

Open Access

https://doi.org/10.1128/iai.00962-19

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Abstract

Borrelia burgdorferi sensu lato, the causative agent of tick-borne Lyme borreliosis (LB), has a limited metabolic capacity and needs to acquire nutrients, such as amino acids, fatty acids, and nucleic acids, from the host environment. Using X-ray crystallography, liquid chromatography-mass spectrometry, microscale thermophoresis, and cellular localization studies, we show that basic membrane protein D (BmpD) is a periplasmic substrate-binding protein of an ABC transporter system binding to purine nucleosides. Nucleosides are essential for bacterial survival in the host organism, and these studies suggest a key role for BmpD in the purine salvage pathway of B. burgdorferi sensu lato Because B. burgdorferi sensu lato lacks the enzymes required for de novo purine synthesis, BmpD may play a vital role in ensuring access to the purines needed to sustain an infection in the host. Furthermore, we show that, although human LB patients develop anti-BmpD antibodies, immunization of mice with BmpD does not confer protection against B. burgdorferi sensu lato infection.

Highlights

Lyme borreliosis (LB) is a tick-borne infectious disease that is prevalent in North American, European, and Asian countries with moderate climates [1,2,3]
We recently showed that the four members of a paralogous basic membrane protein (Bmp) family of B. burgdorferi sensu stricto, namely, BmpA, BmpB, BmpC, and basic membrane protein D (BmpD) (BB0383, BB0382, BB0384, and BB0385, respectively), belong to the substrate-binding protein (SBP) of an ATP-binding cassette (ABC) transporter family (Fig. 1B) [17]
Our results indicate that BmpD functions as an SBP of the ABC-type transporter family, importing purine nucleosides from the environment into the bacterial cell

Summary

Introduction

Lyme borreliosis (LB) is a tick-borne infectious disease that is prevalent in North American, European, and Asian countries with moderate climates [1,2,3]. The ABC transporters belong to one of the largest families of transporter proteins that use the hydrolysis of ATP to transport various substrates across cell membranes [13] They consist of two transmembrane domains (TMD), forming a translocation channel through the membrane, and two nucleoside-binding domains (NBD), which bind to and hydrolyze ATP (Fig. 1A) [13]. ABC transporters play a vital role in the import of nutrients and require a substrate-binding protein (SBP) to deliver the substrate to the translocation channel formed by the two permeases [14]. We recently showed that the four members of a paralogous basic membrane protein (Bmp) family of B. burgdorferi sensu stricto, namely, BmpA, BmpB, BmpC, and BmpD (BB0383, BB0382, BB0384, and BB0385, respectively), belong to the SBPs of an ABC transporter family (Fig. 1B) [17].

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