Evaluation of the Available Animal Models for Bartonellosis

Main Article Content

Rebekah L. Bullard Emily L. Olsen Mercedes A. Cheslock Monica E. Embers


The diseases caused by the Bartonella genus of bacteria are clinically diverse, difficult to reliably diagnose, and can be challenging to cure.  The study of Bartonelloses has been hampered by the lack of a suitable animal model. Preclinical studies for novel therapeutics and a competent host for vector transmission studies are needed to fill critical knowledge gaps. The studies included here are a representation of in vivo Bartonella research and the challenges this line of research faces. This review examines the current state of available animal models by assessing the success of various model species and strains in Bartonella infection. With a focus on the strengths and weaknesses of current animal models, the importance of these models for improvement of human health and veterinary care is emphasized.


Keywords: Bartonella, host, reservoir, vector, infection, pathology

Keywords: Bartonella, host, reservoir, vector, infection, pathology

Article Details

How to Cite
BULLARD, Rebekah L. et al. Evaluation of the Available Animal Models for Bartonellosis. Medical Research Archives, [S.l.], v. 10, n. 11, nov. 2022. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/3282>. Date accessed: 29 mar. 2023. doi: https://doi.org/10.18103/mra.v10i11.3282.
Research Articles


1. Billeter SA, Miller MK, Breitschwerdt EB, Levy MG. Detection of two Bartonella tamiae-like sequences in Amblyomma americanum (Acari: Ixodidae) using 16S-23S intergenic spacer region-specific primers. J Med Entomol. 2008;45:176-179. doi:10.1093/jmedent/45.1.176
2. Prutsky G, Domecq JP, Mori L, et al. Treatment outcomes of human bartonellosis: a systematic review and meta-analysis. Int J Infect Dis. Oct 2013;17:e811-9. doi:10.1016/j.ijid.2013.02.016
3. Angelakis E, Raoult D. Pathogenicity and treatment of Bartonella infections. Int J Antimicrob Agents. Jul 2014;44(1):16-25. doi:10.1016/j.ijantimicag.2014.04.006
4. Kosek M, Lavarello R, Gilman RH, et al. Natural History of Infection with Bartonella bacilliformis in a Nonendemic Population. The Journal of Infectious Diseases. 2000;182:865-72.
5. Garcia-Quintanilla M, Dichter AA, Guerra H, Kempf VAJ. Carrion's disease: more than a neglected disease. Parasit Vectors. Mar 26 2019;12(1):141. doi:10.1186/s13071-019-3390-2

6. Centers for Disease Control and Prevention NCfEaZID, Division of Vector-Borne Diseases. Bartonella henselae infection or cat scratch disease (CSD). Updated January 10, 2022. Accessed July 20, 2022, 2022.
7. Ohl ME, Spach DH. Bartonella quintana and Urban Trench Fever. Clinical Infectious Diseases. 2000;31(1):131-135. doi:10.1086/313890
8. Ghashghaei R, Thung I, Lin GY, Sell RE. Bartonella endocarditis. J Cardiol Cases. Jan 2016;13(1):1-3. doi:10.1016/j.jccase.2015.08.011
9. Akram S, Anwar M, Thandra K, Al. E. Bacillary Angiomatosis. StatPearls. StatPearls Publishing; 2021.
10. Claasens S, Schwartz IS, Jordaan HF, Schneider JW. Bacillary angiomatosis presenting with polymorphic skin lesions. IDCases. 2016;6:77-78. doi:10.1016/j.idcr.2016.10.001
11. Alkan S, Orenstein JM. Bacillary peliosis hepatis. N Engl J Med. May 23 1991;324(21):1513-4. doi:10.1056/nejm199105233242116
12. Corral J, Robles AM, Caire ST, Hernández-Castro R, Moreno-Coutiño G. First Report of Bacillary Angiomatosis by Bartonella elizabethae in an HIV-Positive Patient. American Journal of Dermatopathology. 2019;41:750-753. doi:10.1097/DAD.0000000000001439
13. Schwensen JF, Nielsen RH, Helleberg M. Bacillary angiomatosis in a solid organ transplant recipient. IDCases. 2019;18doi:10.1016/j.idcr.2019.e00649
14. Mitchell BM, Font RL. Molecular Detection of Bartonella henselae for the Diagnosis of Cat Scratch Disease and Bacillary Angiomatosis of the Conjunctiva. Cornea. 2011;30(7):807-814. doi:10.1097/ICO.0b013e318201440c
15. Organization WH. Report of an informal expert consultation SEARO, New Delhi, 7–8 April 2014. 2014.
16. Bosler EM, Ormiston BG, Coleman JL, Hanrahan JP, Benach JL. Prevalence of the Lyme Disease Spirochete in Populations of White-Tailed Deer and White-Footed Mice. Yale Journal of Biology and Medicine. 1984;57(4):651-659.
17. Magnarelli LA, Anderson JF, Chappell WA. Geographic Distributions of Humans, Raccoons, and White-Footed Mice with Antibodies to Lyme Disease Spirochetes in Connecticut. Yale Journal of Biology and Medicine. 1984;57:619-626.
18. Alvarez-Fernandez A, Breitschwerdt EB, Solano-Gallego L. Bartonella infections in cats and dogs including zoonotic aspects. Parasites & vectors. 2018;11:624.
19. Marignac G, Barrat F, Chomel B, et al. Murine model for Bartonella birtlesii infection: New aspects. Comparative Immunology, Microbiology and Infectious Diseases. 2010; 33: 95-107. doi: 10.1016/j.cimid.2008.07.011
20. Colton L, Kabeya H, Kosoy M. Experimental infection of three laboratory mouse stocks with a shrew origin Bartonella elizabethae strain: an evaluation of bacterial host switching potential. Infection Ecology & Epidemiology. 2012;2(1)doi:10.3402/iee.v2i0.17132
21. Colton L, Zeidner N, Lynch T, Kosoy MY. Human isolates of Bartonella tamiae induce pathology in experimentally inoculated immunocompetent mice. BMC Infectious Diseases. 2010;10(229) doi: 10.1186/1471-2334-10-229
22. Reis C, Cote M, Le Rhun D, et al. Vector Competence of the Tick Ixodes ricinus for Transmission of Bartonella birtlesii. PLoS Neglected Tropical Diseases. 2011; 5(5):e 1186. doi: 10.1371/journal.pntd.0001186
23. da Silva MN, Vieira-Damiani G, Ericson ME, et al. Acute and Late Bartonella henselae Murine Model Infection. Vector-Borne and Zoonotic Diseases. 2017; 17(3): 206-208. doi:10.1089/vbz.2016.2007
24. da Silva MN, Vieira-Damiani G, Ericson ME, et al. Bartonella henselae transmission by blood transfusion in mice. Transfusion. Jun 2016;56(6 Pt 2):1556-1559. doi:10.1111/trf.13545
25. Kabeya H, Tsunoda E, Maruyama S, Mikami T. Immune Responses of Immunocompetent and Immunocompromised Mice Experimentally Infected with Bartonella henselae. Journal of Veterinary Medical Science. 2003; 65(4): 479-484. doi: 10.1292/jvms.65.479
26. Boulouis HJ, Barrat F, Bermond D, et al. Kinetics of Bartonella birtlesii Infection in Experimentally Infected Mice and Pathogenic Effect on Reproductive Functions. Infection and Immunity. 2001; 69(9):5313-5317. doi:10.1128/IAI.69.9.5313-5317.2001
27. Karem KL, Dubois KA, McGill SL, Regnery RL. Characterization of Bartonella henselae-specific immunity in BALB/c mice. Immunology. 1999; 97: 352-358. doi: 10.1046/j.1365-2567.1999.00750.x
28. Kunz S, Oberle K, Sander A, Bogdan C, Schleicher U. Lymphadenopathy in a Novel Mouse Model of Bartonella-Induced Cat Scratch Disease Results from Lymphocyte Immigration and Proliferation and Is Regulated by Interferon-α/β. The American Journal of Pathology. 2008;172(4):1005-1018. doi:10.2353/ajpath.2008.070591
29. Regnath T, Mielke MEA, Arvand M, Hahn H. Murine Model of Bartonella henselae Infection in the Immunocompetent Host. Infection and Immunity. 1998; 66(11): 5534-5536. doi: 10.1128/iai.66.11.5534-5536.1998
30. Arvand M, Ignatius R, Regnath T, Hahn H, Mielke MEA. Bartonella henselae-Specific Cell-Mediated Immune Responses Display a Predominantly Th1 Phenotype in Experimentally Infected C57BL/6 Mice. Infection and Immunity. 2001; 69(10): 6427-6433. doi:10.1128/IAI.69.10.6427-6433.2001
31. Colton L, Kosoy M. Experimental infection of laboratory mice with two Bartonella tribocorum strains from wild Mus species: A homologous host-bacteria model system at the genus level. Parasitology. 2013;140:61-68. doi:10.1017/S0031182012001333
32. Pagliuca C, Cicatiello AG, Colicchio R, et al. Novel Approach for Evaluation of Bacteroides fragilis Protective Role against Bartonella henselae Liver Damage in Immunocompromised Murine Model. Frontiers in Microbiology. 2016;7 doi: 10.3389/fmicb.2016.01750
33. Choi EW, Lee HW, Lee JS, Kim IY, Shin JH, Seong JK. Ahnak-knockout mice show susceptibility to Bartonella henselae infection because of CD4+ T cell inactivation and decreased cytokine secretion. BMB Reports. 2019;52(4):289-294. doi:10.5483/BMBRep.2019.52.4.310
34. Griffin B, Baker HJ. Domestic Cats as Laboratory Animals. Laboratory Animal Medicine. 2002;7:50015-6.
35. Breitschwerdt EB. Bartonellosis, One Health and all creatures great and small. Vet Dermatol. 2017;28:96-e21.
36. Kordick DL, Wilson KH, Sexton DJ, Hadfield TL, Berkhoff HA, Breitschwerdt EB. Prolonged Bartonella bacteremia in cats associated with cat-scratch disease patients. J Clin Microbiol. 1995;33:3245-3251.
37. Abbott RC, Chomel BB, Kasten RW, et al. Experimental and natural infection with Bartonella henselae in domestic cats. Comp Immunol Microbiol Infect Dis. 1997;20:41-51.
38. Droz S, Chi B, Horn E, Steigerwalt AG, Whitney AM, Brenner DJ. Bartonella koehlerae sp. nov., isolated from cats. Journal of Clinical Microbiology. 1999;37:1117-1122. doi:10.1128/jcm.37.4.1117-1122.1999
39. Gurfield AN, Boulouis HJ, Chomel BB, et al. Coinfection with Bartonella clarridgeiae and Bartonella henselae and with different Bartonella henselae strains in domestic cats. J Clin Microbiol. 1997;35:2120-2123.
40. Margileth AM, Baehren DF. Chest-wall abscess due to cat-scratch disease (CSD) in an adult with antibodies to Bartonella clarridgeiae: case report and review of the thoracopulmonary manifestion of CSD. Clin Infect Dis. 1998;27:353-357.
41. Yamamoto K, Chomel BB, Kasten RW, Hew CM, Weber DK, Lee WI. Experimental infection of specific pathogen free (SPF) cats with two different strains of Bartonella henselae type I: A comparative study. Vet Res. Nov-Dec 2002;33:669-684. doi:10.1051/vetres:2002048
42. Yamamoto K, Chomel BB, Kasten RW, Hew CM, Weber DK, Lee WI. Experimental infection of specific pathogen free cats with two different strains of Bartonella henselae type I: A comparative study. Veterinary research. 2002;33:669-684. doi:10.1051/vetres

43. Kordick DL, Breitschwerdt EB. Relapsing bacteremia after blood transmission of Bartonella henselae to cats. Am J Vet Res. May 1997;58(5):492-7.
44. Kordick DL, Brown TT, Shin K, Breitschwerdt EB. Clinical and Pathologic Evaluation of Chronic Bartonella henselae or Bartonella clarridgeiae Infection in Cats. Journal of Clinical Microbiology. 1999;37(5):1536-1547. doi:10.1128/jcm.37.5.1536-1547.1999
45. Chomel BB, Kasten RW, Stuckey MJ, et al. Experimental infection of cats with Afipia felis and various Bartonella species or subspecies. Veterinary Microbiology. 2014;172:505-510. doi:10.1016/j.vetmic.2014.05.033
46. Diniz PPVP, Morton BA, Tngrian M, et al. Infection of Domestic Dogs in Peru by Zoonotic Bartonella Species: A Cross-Sectional Prevalence Study of 219 Asymptomatic Dogs. PLoS Negl Trop Dis. 2013;7(9):e2393. doi:10.1371/journal.pntd.0002393
47. Brenner EC, Chomel BB, Singhasivanon OU, et al. Bartonella infection in urban and rural dogs from the tropics: Brazil, Colombia, Sri Lanka and Vietnam. Epidemiol Infect. Jan 2013;141(1):54-61. doi:10.1017/S0950268812000519
48. Balakrishnan N, Cherry NA, Linder KE, et al. Experimental infection of dogs with Bartonella henselae and Bartonella vinsonii subsp. berkhoffii. Veterinary Immunology and Immunopathology. 2013;156:153-158. doi:10.1016/j.vetimm.2013.09.007
49. Chomel BB, Ermel RW, Kasten RW, Henn JB, Fleischman DA, Chang C-C. Experimental infection of dogs with various Bartonella species or subspecies isolated from their natural reservoir. Veterinary Microbiology. 2014;168:169-176. doi:10.1016/j.vetmic.2013.11.009
50. Li H, Liu W, Zhang G-Z, et al. Transmission and Maintenance Cycle of Bartonella quintana among Rhesus Macaques, China. Emerging Infectious Diseases. 2013;19(2):297-300. doi:10.3201/eid1902.120816
51. Huang R, Liu Q, Li G, et al. Bartonella quintana infections in Captive Monkeys, China. Emerging Infectious Diseases. 2011;17:1707.
52. O'Rourke LG, Pitulle C, Hegarty BC, et al. Bartonella quintana in cynomolgus monkey (Macaca fascicularis). Emerging Infectious Diseases. 2005;11:1931-1934.
53. Sato S, Kabeya H, Yoshino A, et al. Japanese Macaques (Macaca fuscata) as Natural Reservoir of Bartonella quintana. Emerging Infectious Diseases. 2015;21:2168-2170.
54. Mooser H, Weyer F. Experimental infection of Macacus rhesus with Rickettsia quintana (trench fever). Proc Soc Exp Biol Med. 1953;83:699-701.
55. Li Y-C, Zeng L, Kosoy M, Wu-Chun Cao H. Transmission and Maintenance Cycle of Bartonella quintana among Rhesus Macaques, China. Emerging Infectious Diseases2013. p. 297-300.
56. Zhang P, Chomel BB, Schau MK, et al. A family of variably expressed outer-membrane proteins (Vomp) mediates adhesion and autoaggregation in Bartonella quintana. PNAS. 2004;101:1363-13635.
57. Bentzel DE, Expinosa BJ, Canal E, Blazes DL, Hall ER. Susceptibility of owl monkeys (Aotus nancymaae) to experimental infection with Bartonella bacilliformis. Comparative medicine. 2008;58:76-80.