Bartonella spp. are facultative intracellular bacteria associated with several emerging diseases in humans and animals. B. henselae causes cat-scratch disease and is increasingly associated with several other syndromes, particularly ocular infections and endocarditis. Cats are the main reservoir for B. henselae and the bacteria are transmitted to cats by cat fl eas. However, new potential vectors are suspected of transmitting B. henselae, in particular, Ixodes ricinus, the most abundant ixodid tick that bites humans in western Europe. We used a membranefeeding technique to infect I. ricinus with B. henselae and demonstrate transmission of B. henselae within I. ricinus across developmental stages, migration or multiplication of B. henselae in salivary glands after a second meal, and transmission of viable and infective B. henselae from ticks to blood. These results provide evidence that I. ricinus is a competent vector for B. henselae.

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.

Bartonella spp. are facultative intracellular vector-borne bacteria associated with several emerging diseases in humans and animals all over the world. The potential for involvement of ticks in transmission of Bartonella spp. has been heartily debated for many years. However, most of the data supporting bartonellae transmission by ticks come from molecular and serological epidemiological surveys in humans and animals providing only indirect evidences without a direct proof of tick vector competence for transmission of bartonellae. We used a murine model to assess the vector competence of Ixodes ricinus for Bartonella birtlesii. Larval and nymphal I. ricinus were fed on a B. birtlesii-infected mouse. The nymphs successfully transmitted B. birtlesii to naïve mice as bacteria were recovered from both the mouse blood and liver at seven and 16 days after tick bites. The female adults successfully emitted the bacteria into uninfected blood after three or more days of tick attachment, when fed via membrane feeding system. Histochemical staining showed the presence of bacteria in salivary glands and muscle tissues of partially engorged adult ticks, which had molted from the infected nymphs. These results confirm the vector competence of I. ricinus for B. birtlesii and represent the first in vivo demonstration of a Bartonella sp. transmission by ticks. Consequently, bartonelloses should be now included in the differential diagnosis for patients exposed to tick bites.

Numerous mammal species, including domestic and wild animals such as ruminants, dogs, cats and rodents, as well as humans, serve as reservoir hosts for various Bartonella species. Some of those species that exploit non-human mammals as reservoir hosts have zoonotic potential. Our understanding of interactions between bartonellae and reservoir hosts has been greatly improved by the development of animal models for infection and the use of molecular tools allowing large scale mutagenesis of Bartonella species. By reviewing and combining the results of these and other approaches we can obtain a comprehensive insight into the molecular interactions that underlie the exploitation of reservoir hosts by Bartonella species, particularly the well-studied interactions with vascular endothelial cells and erythrocytes.

SUMMARYNewborn larvae (NBL) and adult (Ad) stage-specifically expressed genes or members of gene families of Trichinella spiralis were identified by suppression subtractive hybridization (SSH). Six cDNA clones were identified as NBL stage-specific, including 1 member of the T. spiralis gene family encoding glutamic acid-rich proteins, 2 clones encoding novel serine proteases, 2 closely related clones encoding proteins that are members of a deoxyribonuclease II (DNase II)-like family and 1 clone with no similarity to known genes. Four stage-specific clones encoding homologues of retinoid X receptor, caveolin, C2H2 type zinc finger protein and a putative protein with no homology to known sequences were obtained from 3-day-old adult worms. One gene specifically up-regulated in the 5-day-old adult worms encoding a putative cuticle collagen was also identified.

The genus Bartonella comprises a unique group of emerging gram-negative, intracellular bacteria that can cause a long-lasting intraerythrocytic bacteremia in their reservoir hosts. In recent years, the widespread occurrence and diversity of these bacteria has been increasingly recognized. This has resulted in a dramatic expansion of the genus Bartonella to 24 currently described species or subspecies, among which at least half have been associated with human disease. Bartonella infections have been observed in virtually all species examined, extending from humans to carnivores, ungulates, rodents, lagomorphs, insectivores, and bats. Adaptation by Bartonellae to such a diverse range of mammals has resulted in host specificity, and all validated Bartonella species described to date are capable of parasitizing only a limited number of animal species. In this review, the possible mechanisms explaining the specificity of each Bartonella species for its reservoir host are discussed.

To further assess the geographic occurrence, possible vectors, and prevalence of Candidatus Neoehrlichia mikurensis, we analyzed spleen tissues from 276 voles trapped close to human settlements in France; 5 were infected with the organism. Sequencing showed the isolates carried the same genotype as the bacteria that caused disease in humans and animals elsewhere in Europe.

Experimental inoculation of sheep with bovine leukaemia virus (BLV), a retrovirus homologous to the human T-lymphotropic virus type 1 (HTLV-1), induces a chronic expansion of the B lymphocyte population (persistent lymphocytosis) and the development of a B cell leukaemia/lymphosarcoma syndrome. To gain insight into the mechanisms of BLV-induced lymphocytosis, we tested B cell survival capacity and cycling activity in peripheral blood mononuclear cells (PBMCs) from lymphocytotic, asymptomatic and control sheep. Interestingly, B cells from lymphocytotic sheep presented a lower level of spontaneous apoptosis (29%) in ex vivo cultures compared to that obtained with infected asymptomatic (42%) and control (57%/o) sheep PBMCs. Virus capsid (CA) synthesis was mainly found among surviving B cells and the percentage of CA-producing B cells correlated with the extent of B cell survival, indicating that BLV replication in B lymphocytes may promote protection from cell death. B cell survival was not linked with increases in expression of Bcl-2 mRNA or membrane leukosialin (CD43), although both are documented to be involved in some aspects of the B cell life-span. Finally, cell cycle analyses in freshly isolated PBMCs from lymphocytotic sheep revealed a slightly increased proportion of B cells in S phase compared to controls. Altogether, these data suggest that both BLV-induced B cell proliferation and extended survival are involved in the lymphocytotic stage encountered in BLV infection in sheep.