Research

The genus Bartonella comprises several emerging human pathogens affecting diverse groups of people. Carrion’s disease, caused by B. bacilliformis, is a biphasic human vascular disease which presents as a severe hemolytic anemia, and later as angiomatous lesions similar to those attributed to other Bartonella species. B. henselae, the agent of cat-scratch disease, and B. quintana, the agent of trench fever, are also recognized as agents of bacillary angiomatosis in immunocompromised patients. Bartonella species have also been found to cause endocarditis.

The severe acute anemia of Carrion’s disease is unique to B. bacilliformis infection. B. bacilliformis can be seen on erythrocytes of symptomatic patients, implying a central role for erythrocyte interaction in pathogenesis. Research in my laboratory is directed toward the purification and identification of specific Bartonella proteins that appear to play a role in disease pathogenesis specifically related to the development of anemia. One protein, termed deformin, causes pits and indentations in erythrocyte membranes, and another is a slow-acting contact-dependent hemolysin. These factors may be used by the bacterium to enter and/or exit erythrocytes, or to aid in the acquisition of nutrients, such as heme and iron.

Biochemical techniques are employed in the purification of the proteins from bacterial supernatants and/or membranes. The encoding genes are cloned using probes based on peptide sequence data. DNA from clones will be sequenced and searched for homology to known proteins. Purified proteins and specific antibodies will allow direct study of their action on erythrocytes, aiding our understanding of how specific bacterial products cause pathological effects on erythrocytes and other cells of the blood. Understanding the mechanisms of action of the deforming and hemolytic factors will help to define the molecular nature of the interaction of Bartonella and its unusual niche.