Department of Medical Microbiology and Immunology, Texas A&M University System Health Science Center, College Station, Texas 77843-1114, USA
Address for correspondence: J.E. Samuel, Department of Medical Microbiology and Immunology, 407 Reynolds Medical Building, Texas A&M University System Health Sciences Center, College Station, Texas 77843-1114, USA. Voice: 979-862-1684; fax: 979-845-3479.
jsamuel{at}tamu.edu.
Ann. N.Y. Acad. Sci. 990: 653-663 (2003).
The agent of acute and chronic Q fever,
Coxiella burnetii, occupies
a unique niche among intracellular pathogens. The mechanisms
the organism employs to cause disease are unclear but involve
persistence in a parasitophorous vacuole and the subsequent
host response. Studies designed to model molecular mechanisms
of pathogenesis have relied upon indirect evidence for testing
the role of virulence factors since methods for generation of
defined mutations have not been developed. Evidence suggests
replication involving a developmental lifecycle is critical
for intra- and extracellular survival but this cycle is incompletely
defined. It has been proposed that survival in the phagolysosomal-like
parasitophorous vacuole requires specific iron uptake systems,
secretion of enzymes to detoxify the compartment (catalase and
SOD), and down-regulation of an oxidative burst (acid phosphatase).
Studies to test these potential virulence mechanisms can be
accelerated with the recent development of the complete genome
sequence for the prototype acute disease isolate, Nine Mile.
Proteins differentially expressed during the developmental cycle
can more readily be identified with MALDI-TOF description of
proteomic profiles. Genes encoding secreted Cu/Zn SOD, catalase,
and acid phosphatase are predicted and can be tested for function
and expression. An iron regulon is predicted based upon Fur-regulated
open reading frames. The specific role the iron-regulated genes
play in iron acquisition can be tested. Confirmation of the
iron regulon and others can be tested using microarrays based
upon the genomic ORF predictions. These are examples of how
we are rapidly changing the experimental approaches used to
investigate
C. burnetii to improve our understanding of the
biology of this unusual and highly adapted organism.
