The Trw Type IV Secretion System of Bartonella Mediates Host-Specific Adhesion to Erythrocytes

Abstract

Bacterial pathogens typically infect only a limited range of hosts; however, the genetic mechanisms governing host-specificity are poorly understood. The α-proteobacterial genus Bartonella comprises 21 species that cause host-specific intraerythrocytic bacteremia as hallmark of infection in their respective mammalian reservoirs, including the human-specific pathogens Bartonella quintana and Bartonella bacilliformis that cause trench fever and Oroya fever, respectively. Here, we have identified bacterial factors that mediate host-specific erythrocyte colonization in the mammalian reservoirs. Using mouse-specific Bartonella birtlesii, human-specific Bartonella quintana, cat-specific Bartonella henselae and rat-specific Bartonella tribocorum, we established in vitro adhesion and invasion assays with isolated erythrocytes that fully reproduce the host-specificity of erythrocyte infection as observed in vivo. By signature-tagged mutagenesis of B. birtlesii and mutant selection in a mouse infection model we identified mutants impaired in establishing intraerythrocytic bacteremia. Among 45 abacteremic mutants, five failed to adhere to and invade mouse erythrocytes in vitro. The corresponding genes encode components of the type IV secretion system (T4SS) Trw, demonstrating that this virulence factor laterally acquired by the Bartonella lineage is directly involved in adherence to erythrocytes. Strikingly, ectopic expression of Trw of rat-specific B. tribocorum in cat-specific B. henselae or human-specific B. quintana expanded their host range for erythrocyte infection to rat, demonstrating that Trw mediates host-specific erythrocyte infection. A molecular evolutionary analysis of the trw locus further indicated that the variable, surface-located TrwL and TrwJ might represent the T4SS components that determine host-specificity of erythrocyte parasitism. In conclusion, we show that the laterally acquired Trw T4SS diversified in the Bartonella lineage to facilitate host-restricted adhesion to erythrocytes in a wide range of mammals.

Host Specificity of Bacterial Pathogens

“…Cell culture has been useful for understanding the basis of host specificity in hemotropic Bartonella spp. The ability to adhere to and invade erythrocytes from humans, cats, mice, or rats recapitulates the host specificity of B. quintana, B. henseleae, B. tribocorum, and B. birtlesii observed in vivo (Vayssier-Taussat et al 2010). The ability of Bartonella to infect specific hosts appears to be encoded within the Trw type-IV secretory system of these pathogens.…”

Distinct Host Species Correlate with Anaplasma phagocytophilum ankA Gene Clusters

“…Although the exact function of AnkA has not been determined yet, it is suggested to be a T4SS-translocated effector protein of A. phagocytophilum (51) and might therefore be involved in host adaptation, as has been shown for the T4SSs of Bartonella spp. (54,70).…”

Directed shotgun proteomics guided by saturated RNA-seq identifies a complete expressed prokaryotic proteome

“…6B). In contrast, many proteins of the Trw complex, a second B. henselae T4SS that is essential for the infection of erythrocytes (Vayssier-Taussat et al 2010) but dispensable under the conditions studied, were not detected (nine of 24, 38%) (Fig. 5, first and fifth ring), nor was their expression regulated (Supplemental Fig.…”