Borrelia Sulfate Transport Anti-sigma Antagonist Domain-containing Protein (BsaP) Impacts Host-dependent Adaptation of Borrelia Burgdorferi

Date

2021

Authors

Moy, Brian Edward

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Abstract

Borrelia burgdorferi, the agent of Lyme disease, is transmitted to humans and other mammalian hosts via the bite of infected Ixodes scapularis ticks. B. burgdorferi exhibits significant differential gene and protein expression facilitating adaptation to highly disparate conditions before and after the ingestion of a blood meal by ticks. While RpoS (Sigma38) and rpoS-regulated genes play a key role in the transition of spirochetes to mammalian hosts, additional regulatory proteins such as Borrelia oxidative stress Regulator (BosR), Borrelia host adaptation Regulator and RNA chaperone (Hfq), among others, interface with rpoS for optimal "fitness" of B. burgdorferi for transmission, survival, and colonization between and within hosts. In addition, the borrelial genome encodes for a 103-residue homolog with a conserved serine residue at position 55, designated as Borrelia Sulfate Transport Anti-Sigma Antagonist domain-containing Protein (BsaP) that when constitutively hyper-expressed reduces levels of RpoS, BosR and several rpoS-regulated lipoproteins. BsaP is co-transcribed as part of a chemotaxis operon and is induced at fed-tick mimicking conditions. Deletion of bsaP results in loss of infectivity in C3H/HeN mice and reduced acquisition and survival during the tick phase of infection. There was a significant reduction in the levels of RpoS and rpoS-regulated lipoproteins providing a basis for the attenuation of infection in a mammalian host. Serine to alanine substitution at position 55 alters the antigenic protein profile of B. burgdorferi, impacting the regulatory effects of BsaP, possibly through activation/ inactivation of BsaP via phosphorylation of this conserved serine residue, which then goes on to affect rpoS-dependent gene regulation directly or indirectly. BsaP is a novel post-transcriptional regulator influencing optimal levels of proteins for survival and colonization of B. burgdorferi during the mammalian and tick phases of infection.

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Keywords

Bacterial Gene Regulation, Borrelia burgdorferi, Lyme Disease, STAS domain

Citation

Department

Integrative Biology