Type IV Effector Secretion and Subversion of Host Functions by Bartonella and Brucella Species

Abstract

Bartonella and Brucella species comprise closely related genera of the order Rhizobiales within the class α-proteobacteria. Both groups of bacteria are mammalian pathogens with a facultative intracellular lifestyle and are capable of causing chronic infections, but members of each genus have evolved broadly different infection and transmission strategies. While Brucella spp. transmit in general via the reproductive tract in their natural hosts, the Bartonella spp. have evolved to transmit via arthropod vectors. However, a shared feature of both groups of pathogens is their reliance on type IV secretion systems (T4SSs) to interact with cells in their mammalian hosts. The genomes of Bartonella spp. encode three types of T4SS, Trw, Vbh/TraG, and VirB/VirD4, whereas those of Brucella spp. uniformly contain a single T4SS of the VirB type. The VirB systems of Bartonella and Brucella are associated with distinct groups of effector proteins that collectively mediate interactions with host cells. This chapter discusses recent findings on the role of T4SS in the biology of Bartonella spp. and Brucella spp. with emphasis on effector repertoires, on recent advances in our understanding of their evolution, how individual effectors function at the molecular level, and on the consequences of these interactions for cellular and immune responses in the host.

Role of distinct type‐IV‐secretion systems and secreted effector sets in host adaptation by pathogenicBartonellaspecies

“…Interestingly, the distributional pattern of VirB/VirD4‐T4SSs and Beps correlates with the blood‐feeding behaviour and proposed mode of transmission by the arthropod vectors considered competent for bacterial transmission (Dehio & Tsolis, ). Bartonellae lacking a VirB/VirD4‐T4SS (i.e., B. bacilliformis and L2 species) are exclusively transmitted by biting diptera (sandflies, biting flies, or keds) that display a forceful mode of blood‐feeding with significant skin damage and bleeding of capillaries.…”

“…The Bep arsenals found in B. ancashensis (L1) and in species of L3 and L4 arose three times through independent duplication events from a single, primordial FIC-BID effector, followed by a cascade of gene duplication and diversification events (Figure 2;Siamer & Dehio, 2015;Dehio & Tsolis, 2017;Harms, Liesch, et al, 2017a). Initially, it was proposed that the FIC-BID-toxin VbhT represents a missing link in the evolution of Beps (Siamer & Dehio, 2015).…”

“…These arthropods display a more subtle blood‐feeding behaviour that does not lead to capillary damage and thus not to a direct route for the bacteria to enter the blood stream. Rather, these bartonellae are superficially inoculated into the dermis by scratching and biting (Dehio & Tsolis, ; Siamer & Dehio, ), which necessitates that bacteria colonise additional host niches before reaching the blood. We therefore hypothesize that the independent acquisition of the VirB/VirD4‐T4SS in B. ancashensis and the last common ancestors of L3 and L4, represents an adaptive trait and evolutionary key innovation that provided novel ecological opportunities to the bartonellae, that is, vector competence for arthropods with bacterial transmission relying on systematic spread of infection from a dermal site of inoculation.…”

Comparative Ecology of Bartonella and Brucella Infections in Wild Carnivores

“…Infections caused by bacteria of both taxonomic groups can lead to a long-lasting bacteremia with ability to invade specific mammalian cells and survive inside them. Via analogous mechanisms, the specialized secretion system (T4SS) works as a molecular syringe to inject effector molecules into their target cells (18, 19). Bartonella and Brucella modulate their gene expression to adapt to the different environments during the infectious process (20, 21).…”

Bactericidal type IV secretion system homeostasis in Xanthomonas citri

“…Type IV secretion systems (T4SS) are large multiprotein nanomachines spanning both the inner and outer membrane of many Gram-negative bacterial species [1]. The best described functions of T4SSs are the delivery of the T-DNA of Agrobacterium tumefaciens [2,3], their roles in bacterial conjugation [4] and their involvement in delivering virulence factors to mammalian cells by several pathogenic species [5]. T4SSs found in Gram-negative bacteria are made up of over 100 subunits of 12 different proteins (VirB1 to VirB11 plus VirD4) with a total size of over 3 MDa each [1] though some bacterial species carry systems with extra components and are much larger in size [6,7].…”