Research Description:
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The emergence and reemergence of pathogenic microorganisms has become a matter
of significant concern to the medical community. Research in my laboratory is
centered on the genus Bartonella, a group of Gram-negative bacilli which have
recently attracted the attention of those interested in human diseases. Bartonella
henselae was first identified about a decade ago in lesions of AIDS patients
and other immunocompromised individuals. Subsequently, it was found to be the
agent responsible for Cat Scratch Disease, a debilitating fever that affects up
to 22,000 Americans per year. Bartonella bacilliformis is the causative
agent of human bartonellosis, a disease endemic to the Andes region of South America.
Bartonellosis is characterized by an acute phase resulting in severe hemolytic
anemia followed by a secondary phase producing nodules on the skin and internal
organs. If untreated, bartonellosis has a fatality rate of 80-90%. Bartonella
quintana causes Trench Fever, a condition that was a significant problem
for soldiers during World War I and has recently reappeared among urban homeless
populations.
The focus of our research is the molecular characterization of Bartonella
species. Our ultimate objectives are: 1) to determine the molecular basis for
pathogenesis by these organisms, and 2) to develop tests for the species-specific
diagnosis of bartonella infections. As a first step toward these goals, we isolated
several immunoreactive clones from a genomic library of B. bacilliformis
by screening the library with serum from a bartonellosis patient. We found that
one of these clones codes for a homolog of FtsZ, a cell division protein that
is highly conserved among prokaryotes. The FtsZ protein from B. bacilliformis
is about twice the size of the homologs from most other bacteria, containing
a unique C-terminal region that is responsible for the immunoreactive properties
of the protein. We subsequently cloned and characterized the ftsZ genes from
B. henselae and B. quintana and found that these genes also code for an extended
sequence at the C-terminal end. The FtsZ proteins from the three bartonella
strains exhibit a high degree of sequence identity (81-83%), with most of the
sequence divergence localized to the C-terminal half of the proteins. By designing
oligonucleotides and synthetic peptides corresponding the regions of highest
sequence divergence, we have developed PCR- and serologically-based diagnostic
tests that accurately and efficiently distinguish among the different bartonella
species.
We are continuing our molecular analysis of bartonellae through two primary
approaches:
a. Characterization of additional clones coding for immunoreactive bartonella
proteins.
b. Isolation of additional bartonella proteins that are homologs of cell division
proteins identified in other bacteria, including FtsA and FtsQ.
c. Investigation of gene organization and expression through the characterization
of bartonella fts operons.
Negatively stained electron micrographs of R. henselae showing attached
bacteriophage-like particles (arrow).
Recent Publications:
Kirma, N., Ferreira, J.L., and Baumstark, B.R. (2004). Characterization of six type A strains of Clostridium botulinum that contain type B toxin gene sequences. FEMS Micro Lett. 231, 159-164.
Lee, K.N., Padmalayam, I., Baumstark, B.R., Baker, S.L., and Massung, R.F. (2003). Characterization of the ftsZ gene from Ehrlichia chaffeensis, Anaplasma phagocytophilum, and Rickettsia rickettsii, and use as a differential PCR target. DNA Cell Biol 22, 179-186.
Padmalayam, I., Fiskus, W., Massung, R.F., and Baumstark, B.R. (2003). Molecular cloning and analysis of a region of the Bartonella bacilliformis genome encoding NlpD, L-isoaspartyl methyltransferase and YajC homologs. DNA Cell Biol 22, 347-353.
Fiskus, W., Padmalayam, I., Kelly, T., Guibao, C., and Baumstark, B.R. (2003). Identification and characterization of the ddlB, ftsQ and ftsA genes upstream of ftsZ in Bartonella bacilliformis and Bartonella henselae. DNA Cell Biol. 22, 743-752
Padmalayam, I., Karem, K., Baumstark, B., and Massung, R. (2000). The gene encoding the 17-kilodalton antigen of Bartonella henselae is located within a cluster of genes homologous to the virB virulence operon. DNA Cell Biol 19, 377-382.
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