Molecular Recognition in Biological Systems and Bioinformatics

Bacterial pathogenesis; Vaccine antigens; Bacterial virulence factors; Lipooligosaccharides; Mechanisms iron acquisition and utilization

Haemophilus ducreyi related research projects

We have identified two outer membrane proteins, termed OmpP2a and OmpP2b, which have homology to the major porin of H. influenzae OMP P2. Porins have been shown to be essential bacterial proteins with multiple functions. The genes that code for these proteins have been cloned and sequenced. Subsequent studies have demonstrated that the putative porins are differentially expressed by various clinical isolates of H. ducreyi. The overall goal of this project is to determine the role of these putative porins in the pathogenesis of H. ducreyi infections.

We have recently identified a type 1 fimbria operon in H. ducreyi 35000HP. The gene encoding the major fimbrial filament subunit has been cloned and a fimA-deficient has been constructed. Analysis of this mutant strain will yield important insight into the role of fimbriae in H. ducreyi pathogenesis, particularly as it pertains to colonization of the host tissues.

The third emphasis of our work with H. ducreyi involves microarray analysis specifically analyzing gene expression under varying conditions. The entire chromosome of H. ducreyi strain 35000HP has been sequenced and annotated and a 50mer oligonucleotide array has been developed. We have performed a preliminary study analyzing gene expression at various time points throughout a standard growth curve to demonstrate the effectiveness of the array and also to establish baseline levels as a guide for future studies.

Acinetobacter baumannii related research projects

A. baumannii is a Gram-negative pathogen, that is largely associated with nosocomial infections in susceptible populations. These usually involve post-operative individuals requiring ventilator assisted breathing systems. The organisms isolated from these patients often exhibit a high degree of antibiotic resistance. Recently, the military has seen an increased prevalence of multi-drug resistant Acinetobacter-infections in wounded soldiers returning from the Iraq and Afghanistan regions creating interest in studying this under-characterized pathogen.

The biosynthesis and expression of the lipopolysaccharide (LPS) molecule of A. baumannii is a new research focus of our laboratory. LPS is a common constituent of the outer membrane of Gram-negative bacteria and studies are underway to define the role of LPS in the pathogenesis in A. baumannii infections. Using random transposon mutagenesis, we have identified a gene locus involved in O-antigen biosynthesis. Studies of defined mutants that can no longer express full-length LPS molecules will yield important insights into the virulence of this opportunistic pathogen.

Our second major focus of research with A. baumannii involves the identification and characterization of conserved, surface-exposed virulence factors. We have utilized the A. baumannii genome sequence in the NCBI database to select putative targets with homologies to other well-known bacterial components shown to be important in pathogenesis. These studies will lead to a better understanding of how A. baumannii establishes colonization on human mucosal surfaces.

Moraxalla catarrhalis, Acinetobacter baumannii, Haemophilus ducreyi

• Pilus
• Filamentous hemmaggluttinin
• Lipooligosaccharides/lipopolysaccharides
• Porins
• Iron-regulated proteins/receptors
• Heat shock protein

Otitis media (middle ear infection), pneumonia, deep tissue wounds (battlefield required), exacerbations of COPD, Respiratory infections, STDs

• prokaryotic molecular biology techniques
• transformation/mutagenesis
• protein expression
• monoclonal antibody development and analysis

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