# SURFACE CHANGE AND VIRULENCE IN COXIELLA BURNETII

> **NIH NIH R01** · WASHINGTON STATE UNIVERSITY · 1993 · $261,056

## Abstract

Coxiella burnetii is the causative agent of both acute Q fever and chronic
endocarditis in humans.  Both plasmid and chromosomal differences correlate
with the type of disease (acute or chronic) caused by an isolate suggesting
that the different isolates have different virulence determinants.  We have
designed experiments to extend our knowledge of C. burnetii genomic and
plasmid DNA and their relationship to disease.  Unique plasmid regions will
be analyzed by cloning, restriction enzyme, Southern hybridization and
sequencing analyses.  We will also identify the plasmid origin of
replication for studies on transformation and mutagenesis of C. burnetii.
Plasmid encoded surface proteins (possible virulence factors) will be
identified by looking for protease-sensitive surface proteins produced by
maxicells containing pUC/C. burnetii plasmid constructs and also by TnphoA
mutagenesis.  We will identify chromosomal encoded surface antigens
employing both cosmid and 1 ZapII gene libraries in E. coli, by screening
for colonies/plaques reacting with C. burnetii-specific antisera and
monoclonal antibodies to isolates with differing disease potential.  The
distribution of antigens in C. burnetii isolates will be determined using
surface iodination, PAGE, and western analyses.  To understand the role of
gene in virulence and intracellular growth of C. burnetii, we have designed
experiments to evaluate gene function directly within the organism.  We
will use previously cloned C. burnetii chromosomal and plasmid genes as
specific probes to assay their transcriptional activation at different
times and under different conditions, in vitro and in vivo.  Concurrently,
we will examine qualitative differences in C. burnetii RNA production.
Genes specifying unique or differentially expressed transcripts produced at
different time points in vitro or post-infection will be cloned and
sequenced.  Proteins being synthesized under these conditions will also be
evaluated by 1 and 2 -D PAGE.  In this fashion we will develop an
understanding of gene expression in C. burnetii during the host-parasite
interaction.  We also will examine plasmids and the chromosome for
alternative virulence functions; factors that enhance intracellular
survival and growth and thus pathogenesis.  We will clone genes encoding
key metabolic functions as well as those shown to be important for
intracellular survival of other organisms.  These genes will be cloned from
C. burnetii employing the methods of PCR, mutant complementation and using
homologous genes as probes.  And because the development of genetic
exchange systems is vital to an understanding of rickettsial genetic
mechanisms, we will continue to develop transformation and mutagenesis
systems for C. burnetii using electroporation and antibiotic selection in
cell cultures.

## Key facts

- **NIH application ID:** 3129694
- **Project number:** 5R01AI020190-11
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **SAM.gov UEI:** XRJSGX384TD6
- **Principal Investigator:** LOUIS P MALLAVIA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $261,056
- **Award type:** 5
- **Project period:** 1983-07-01 → 1996-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129694

## Citation

> US National Institutes of Health, RePORTER application 3129694, SURFACE CHANGE AND VIRULENCE IN COXIELLA BURNETII (5R01AI020190-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129694. Licensed CC0.

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