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Bartonella Species as Human Pathogens

The two human pathogens B. quintana and B. bacilliformis and the feline species B. henselae are responsible for most human Bartonella infections. In addition to these, at least five other species have been associated with human disease [23]. Disease manifestations depend on the immune status of the host; in an immunocompetent individual the infection has only local symptoms and can usually be controlled, whereas it can have a severe outcome in an immunocompromised person.

B. quintana is the causative agent of trench fever, a disease that affected more than one million soldiers during World War I and is now reemerging among homeless and alcoholic individuals. However, many infected persons develop a chronic asymptomatic carrier state. The bacteria are transmitted among humans via the human body louse, and may persist in the blood long after all clinical signs have disappeared. In immunocompromised individuals, especially HIV-infected patients, B. quintana can cause bacillary angiomatosis. Symptoms include tumorlike lesions of the skin, and the infection is usually fatal unless treated with antibiotic therapy. Like B. quintana, B. henselae can also cause bacillary angiomatosis in immunocompromised persons and induce vascular proliferation in the liver and the spleen (bacillary peliosis), resulting in the formation of blood-filled cysts.

B. bacilliformis is the agent of Carrion's disease, the spread of which is limited to the areas where the sand fly is found, primarily the Peruvian Andes. Carrion's disease is a biphasic disease consisting of an acute, highly fatal febrile anemia resulting from the invasion of erythrocytes, and a chronic phase where bacteria colonize the vascular endothelium and cause vasoproliferative eruptions of the skin. B. bacilliformis is probably the only Bartonella species that triggers hemolysis, i.e., the rupture of erythrocytes [29].

B. quintana, B. bacilliformis, and B. henselae are unique among all bacterial pathogens in that they induce proliferation of their host cells. Several strategies are involved: in addition to stimulating proliferation of endothelial cells, these bacteria are also able to inhibit endothelial cell apoptosis [33] and induce proinflammatory activity through activation of the transcription factor NF-jB [34]. The resulting tumor-like lesions normally comprise proliferating endothelial cells, bacteria, and infiltrates of macrophages/monocytes and neutrophils. A nonfimbral adhesin, designated Bartonella adhesin (BadA), or variably expressed outer membrane proteins (Vomp) mediate binding to endothelial cells and is immunodomi-nant in infected patients, with a potential role in the induction of vasoproliferative disorders [35]. Variable expression of B. quintana Vomp family members in a macaque animal model appears to be mediated by gene deletion [36].

286 | 13 The Genomes of Pathogenic Bartonella Species 13.3

The Bartonella Genomes

Complete genome sequence data are available for B. henselae (Houston-1 strain) and B. quintana (Toulouse strain) [37]. B. henselae and B. quintana are closely related to each other (Fig. 13.1), but differ in host and vector preferences. The B. henselae genome is 1.93 Mbp long with 1491 genes, as compared to 1.58 Mbp and 1143 genes in B. quintana. There is a striking similarity in the identity of genes in the different functional categories for B. henselae and B. quintana, with one exception: genes belonging in phage and pathogenicity categories are far more common in B. henselae. Most of these are found on one of three genomic islands or on a prophage, all unique to B. henselae.

The close relatives Brucella melitensis and Brucella suis have two replicons, of 2.1 Mbp and 1.2 Mbp respectively [38, 39]. Both sequenced Bartonella genomes are reduced versions of chromosome I from Brucella. Interestingly, they also contain a segment of approximately 280 kbp in B. henselae and 200 kbp in B. quintana containing Bartonella-specific genes as well as genes showing similarity to genes located on chromosome II of B. melitensis. It is speculated that this segment was acquired by the integration of an auxiliary replicon in a common ancestor of the Bartonella species [37]. The segment has a higher noncoding content than the rest of the genome, in B. quintana mounting to 50%, suggesting that it is being degraded. Because the major difference between the two species is in the chromosome Il-like segment and the genomic islands, these will be discussed in greater detail below.

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