An Immunocompromised Murine Model of Chronic Bartonella Infection

Abstract

Bartonella are ubiquitous Gram-negative pathogens that cause chronic blood stream infections in mammals. Two species most often responsible for human infection, B. henselae and B. quintana, cause prolonged febrile illness in immunocompetent hosts, known as cat scratch disease and trench fever, respectively. Fascinatingly, in immunocompromised hosts, these organisms also induce new blood vessel formation leading to the formation of angioproliferative tumors, a disease process named bacillary angiomatosis. In addition, they cause an endothelial-lined cystic disease in the liver known as bacillary peliosis. Unfortunately, there are as yet no completely satisfying small animal models for exploring these unique human pathologies, as neither species appears able to sustain infection in small animal models. Therefore, we investigated the potential use of other Bartonella species for their ability to recapitulate human pathologies in an immunodeficient murine host. Here, we demonstrate the ability of Bartonella taylorii to cause chronic infection in SCID/BEIGE mice. In this model, Bartonella grows in extracellular aggregates, embedded within collagen matrix, similar to previous observations in cat scratch disease, bacillary peliosis, and bacillary angiomatosis. Interestingly, despite overwhelming infection later in disease, evidence for significant intracellular replication in endothelial or other cell types was not evident. We believe that this new model will provide an important new tool for investigation of

Infections and cardiovascular disease: is Bartonella henselae contributing to this matter?

“…Recently, a murine model of chronic infection in immunocompromised SCID/Beige mice showed the ability of bacteria to recapitulate human pathologies. Indeed, in this model, bacteria grow in extracellular aggregates, embedded within collagen matrix, similar to the observations in BP, BA and cat-scratch disease (Chiaraviglio et al, 2010). Bacterial VirB type IV secretion systems (T4SSs) represent crucial pathogenic factors that have contributed to the Bartonella henselae expansion in nature; in fact, T4SSs facilitate adaptation to mammalian hosts (Schmid et al, 2004;Schülein et al, 2001) by translocation of a cocktail of Bartonella effector proteins (Beps) into host cells (Okujava et al, 2014).…”

“…When Bartonella gains access to the human circulatory system, it disseminates from the point of inoculation and colonizes secondary foci showing preference for highly vascularized tissues like heart valves, liver and spleen (Chiaraviglio et al, 2010). Immediately after, bacteria are released into the blood stream, where they efficiently infect erythrocytes and also reinfect the primary niche (Fig.…”

High Prevalence and Genetic Heterogeneity of Rodent-Borne Bartonella Species on Heixiazi Island, China

“…These and previous observations suggest that these organs may act as depositories of harbored Bartonella, although they may be damaged as a result of a long-term Bartonella persistence in these tissues (27). These interactions underlie the primary etiology of Bartonellacaused hepatosplenomegaly and tissue inflammation in humans and some animals, including dogs (28)(29)(30).…”

Experimental-Biological Model of Bartonellosis

“…Therefore, the last years noted tendency to the increase of researches, aimed at the development of technically more suitable models to experimentally reproduce bartonellosіs that are based on the exploitation of the most widespread laboratory animals, -mostly mice, considerably rare-rats, guinea-pigs, rabbits [3,5,8]. It should be noted that for ordinary white nonlinear laboratory mice experimental bartonellosis is characterized with the absence or extraordinarily poorly expressed symptoms of the disease without substantial reproduction and accumulation of causative agents in their organism, and with rapid elimination of them even in the conditions of bacteraemia in experimental animals on the initial stage after their infection.…”

“…Optimal empiric dose of the preparation, fixed by us, is 250 µg/kg. The injection of this dose provides forming of the well expressing and stable immunodeficient state, and it does not result in unforeseeable death of a part (about 12% and more) of experimental animals that were marked with the introduction of 500 µg/kg and more [4,5].…”