Borrelia burgdorferi protein interactions critical for microbial persistence in mammals

Abstract

Borrelia burgdorferi is the causative agent of Lyme disease that persists in a complex enzootic life cycle, involving Ixodes ticks and vertebrate hosts. The microbe invades ticks and vertebrate hosts in spite of active immune surveillance and potent microbicidal responses, and establishes long-term infection utilising mechanisms that are yet to be unravelled. The pathogen can cause multi-system disorders when transmitted to susceptible mammalian hosts, including in humans. In the past decades, several studies identified a limited number of B. burgdorferi gene-products critical for pathogen persistence, transmission between the vectors and the host, and host-pathogen interactions. This review will focus on the interactions between B. burgdorferi proteins, as well as between microbial proteins and host components, protein and non-protein components, highlighting their roles in pathogen persistence in the mammalian host. A better understanding of the contributions of protein interactions in the microbial virulence and persistence of B. burgdorferi would support development of novel therapeutics against the infection.

Keywords: Borrelia burgdorferi; Lyme disease; host persistence; microbial infectivity; protein interactions.

FIGURE 1. Protein interaction involved in Borrelia burgdorferi infection of mammalian hosts transmitted via Ixodes ticks.

B. burgdorferi (Borrelia) is transmitted to the mammalian dermis at the tick-bite site. A spirochete outer surface protein (OspC), via interaction with a tick salivary gland protein (Salp15), carries the latter protein in the dermis where it assists the pathogen evasion of host immune insults. Protection from the vertebrate immune system, as well as dissemination through extracellular matrix or vasculature, is also mediated by interactions between additional sets of B. burgdorferi proteins, like BBK32, CRASP1–5, VlsE, Erp proteins, OspC, BBA70, and Enolase amongst others. The pathogen also uses its chemotaxis machinery system, including several Che proteins to disseminate into the host. The bacteria also use its own protease, BbHtrA, to degrade host extracellular matrix components and promote the infection. During and/or after dissemination to distant tissue locations, spirochetes interact with specific host molecules like matrix metalloproteases (MMP), collagen, or integrins and use specific adhesins like BBK32, DBPA/DBPB, P66, RevA, BBA33, BBB07, BB0172, Erp proteins, and Lmp1, amongst others to colonise the tissues and to facilitate its persistence in the infected organs