Abstract
BackgroundThe bacterial spirochete Borrelia burgdorferi is the causative agent of the most commonly reported arthropod-borne illness in the United States, Lyme disease. A family of proteins containing von Willebrand Factor A (VWFA) domains adjacent to a MoxR AAA+ ATPase have been found to be highly conserved in the genus Borrelia. Previously, a VWFA domain containing protein of B. burgdorferi, BB0172, was determined to be an outer membrane protein capable of binding integrin α3β1. In this study, the characterization of a new VWFA domain containing membrane protein, BB0173, is evaluated in order to define the location and topology of this multi-spanning membrane protein. In addition, functional predictions are made.ResultsOur results show that BB0173, in contrast to BB0172, is an inner membrane protein, in which the VWFA domain is exposed to the periplasmic space. Further, BB0173 was predicted to have an aerotolerance regulator domain, and expression of BB0173 and the surrounding genes was evaluated under aerobic and microaerophilic conditions, revealing that these genes are downregulated under aerobic conditions. Since the VWFA domain containing proteins of B. burgdorferi are highly conserved, they are likely required for survival of the pathogen through sensing diverse environmental oxygen conditions.ConclusionsPresently, the complex mechanisms that B. burgdorferi uses to detect and respond to environmental changes are not completely understood. However, studying the mechanisms that allow B. burgdorferi to survive in the highly disparate environments of the tick vector and mammalian host could allow for the development of novel methods of preventing acquisition, survival, or transmission of the spirochete. In this regard, a putative membrane protein, BB0173, was characterized. BB0173 was found to be highly conserved across pathogenic Borrelia, and additionally contains several truly transmembrane domains, and a Bacteroides aerotolerance-like domain. The presence of these functional domains and the highly conserved nature of this protein, strongly suggests a required function of BB0173 in the survival of B. burgdorferi.
Highlights
The bacterial spirochete Borrelia burgdorferi is the causative agent of the most commonly reported arthropod-borne illness in the United States, Lyme disease
Homology of B. burgdorferi aerotolerance mediating genes and BB0173 protein features Upon investigating open reading frame (ORF) surrounding bb0173 on the B. burgdorferi linear chromosome, other similarities appeared between bb0170 to bb0176 and the equivalent regions of B. fragilis, R. leguminosarum, L. interrogans, and L. biflexa [25]
It has been well documented that Methanol dehydrogenase regulatory ATPase (MoxR) ATPases are found near von Willebrand Factor A (VWFA) domaincontaining proteins [26], and has been observed to be the case in the Borrelia species evaluated in this paper
Summary
The bacterial spirochete Borrelia burgdorferi is the causative agent of the most commonly reported arthropod-borne illness in the United States, Lyme disease. With regards to the endothelial cells, B. burgdorferi has been shown to bind the extracellular matrix (ECM) components (fibronectin, laminin, collagens (type I, III, and IV)) and integrins, among other components, through Borrelial proteins such as BBK32, BBA33, ErpX, P66, BBA07, BB0172, DbpA, DbpB, OspF and Lmp, respectively [7, 8, 10,11,12,13,14,15,16,17,18,19,20] Due to their extracellular exposure and relevance for the persistence of the pathogen in the mammalian host, the characterization of these proteins has potential value to the prevention of Lyme disease as drug and vaccine targets
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