The Borrelia genome consists of a linear chromosome and numerous linear and circular plasmids. Using a computational framework, we examined the plasmid proteome of Borrelia burgdorferi sensu lato to identify potential outer membrane (OM) β-barrel proteins. Our approach identified BBJ25 on plasmid lp38 as an Omp85 superfamily domain with structural homology to BamA/TamA. Analysis of the surrounding genes reveal a cluster of seven genes. Structure-function analysis (AlphaFold3 and DALI) points towards a role in membrane transport, with two chaperone proteins (BBJ23, BBJ24), the Omp85-family domain BBJ25, a homodimeric MacB-like type-VII ABC transporter with an associated ATP-binding domain (BBJ26, BBJ27), a LolA-like domain (BBJ28), and one protein of unknown function (BBJ29). Taken together, this points towards a role in the ATP-driven extraction of a non-polar ligand, possibly lipoproteins, from the inner membrane and delivery to the OM. Structural homology is detected to Escherichia coli proteins involved in lipoprotein sorting (LolACDE). Wider analysis of the Borrelia genus revealed two major variants of this 7-gene cluster, distributed across multiple different linear elements including lp17, lp28, lp38, and the linear chromosome of Borrelia turcica. Borrelia valaisiana was found to have both allelic variants coexisting in the same genospecies on different linear plasmids (lp28-3 and lp28-8). Previous studies have reported up-regulation of these genes in response to mammalian signals. The conservation of these proteins throughout the Borrelia genus, coupled with the occurrence of multiple copies in some genospecies, point towards a critical function. The identity of the target ligand remains uncertain and requires experimental verification.
Nixon et al. (Wed,) studied this question.