Research article

Human isolates of Bartonella tamiae induce pathology in experimentally inoculated immunocompetent mice
Leah Colton , Nordin Zeidner , Tarah Lynch and Michael Y Kosoy

Bacterial Diseases Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO, USA

author email corresponding author email

BMC Infectious Diseases 2010, 10:229doi:10.1186/1471-2334-10-229

The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2334/10/229

Received:
9 February 2010

Accepted:
30 July 2010

Published:
30 July 2010


© 2010 Colton et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract
Background
Bartonella tamiae, a newly described bacterial species, was isolated from the blood of three hospitalized patients in Thailand. These patients presented with headache, myalgia, anemia, and mild liver function abnormalities. Since B. tamiae was presumed to be the cause of their illness, these isolates were inoculated into immunocompetent mice to determine their relative pathogenicity in inducing manifestations of disease and pathology similar to that observed in humans.

Methods
Three groups of four Swiss Webster female mice aged 15-18 months were each inoculated with 106-7 colony forming units of one of three B. tamiae isolates [Th239, Th307, and Th339]. A mouse from each experimental group was sampled at 3, 4, 5 and 6 weeks post-inoculation. Two saline inoculated age-matched controls were included in the study. Samples collected at necropsy were evaluated for the presence of B. tamiae DNA, and tissues were formalin-fixed, stained with hematoxylin and eosin, and examined for histopathology.

Results
Following inoculation with B. tamiae, mice developed ulcerative skin lesions and subcutaneous masses on the lateral thorax, as well as axillary and inguinal lymphadenopathy. B. tamiae DNA was found in subcutaneous masses, lymph node, and liver of inoculated mice. Histopathological changes were observed in tissues of inoculated mice, and severity of lesions correlated with the isolate inoculated, with the most severe pathology induced by B. tamiae Th239. Mice inoculated with Th239 and Th339 demonstrated myocarditis, lymphadenitis with associated vascular necrosis, and granulomatous hepatitis and nephritis with associated hepatocellular and renal necrosis. Mice inoculated with Th307 developed a deep dermatitis and granulomas within the kidneys.

Conclusions
The three isolates of B. tamiae evaluated in this study induce disease in immunocompetent Swiss Webster mice up to 6 weeks after inoculation. The human patients from whom these isolates were obtained had clinical presentations consistent with the multi-organ pathology observed in mice in this study. This mouse model for B. tamiae induced disease not only strengthens the causal link between this pathogen and clinical illness in humans, but provides a model to further study the pathological processes induced by these bacteria.