Department of Microbiology and Immunology
Professor of Microbiology/Immunology and Medicine
Infectious Disease; Microbial Pathogenesis; Microbiology
Our research interests focus on microbial pathogenesis, particularly on the identification and characterization of bacterial virulence factors and putative vaccine antigens for the gram-negative human pathogens: Moraxella catarrhalis and Acinetobacter baumannii.
I. One major area of focus involves the gram-negative human pathogen Moraxella catarrhalis. This bacterium predominantly causes middle ear infections and sinusitis in infants and children, and lower respiratory tract infections in adults. This organism is the third leading cause of otitis media and it is estimated that approximately 50% of children will become colonized by this bacterium in the first six months of life.
M. catarrhalis-related projects ongoing in the lab:
A. One prominent bacterial surface component implicated as a potential virulence factor is the lipooligosaccharide (LOS) molecule. Structural studies show that M. catarrhalis LOS is similar to the LOS of other Gram-negative human mucosal pathogens. Currently there is interest in defining the role of LOS in pathogenesis and in determining the assembly and expression of this major surface glycolipid. The focus of this work is to perform a comprehensive analysis of the genetics and biology of M. catarrhalis LOS.
B. We have now demonstrated that M. catarrhalis express peritrichious type-IV pili. Our studies indicate pilus production by this bacterium is essential for DNA uptake by natural transformation and undergoes iron-responsive regulation. Additional studies will focus on elucidating the prevalence and role of type IV pili in the pathogenesis and host response of M. catarrhalis infections. We have also entered into a collaborative study using a Chinchilla colonization model in order to correlate our in vitro studies with a relevant in vivo biologic system.
C. In addition, we are also attempting to identify specific bacterial factors involved in attachment to host tissues. M. catarrhalis often colonizes the mucosal surfaces in the nasopharynx of young children. There is a strong correlation between colonization and subsequent development of otitis media. We have recently identified a two-partner secretion (TPS) locus in M. catarrhalis termed MCH (M. catarrhalis hemagglutinin-like proteins). The MCH locus consists of three open reading frames: mchA1 and mchA2 encode homologues to the filamentous hemagglutinin of Bordetella pertussis, mchB encodes the TPS transporter. We are currently characterizing this region and are investigating the function of the M. catarrhalis TPS locus.
II. Acinetobacter baumannii, a Gram-negative pathogen, causes nosocomial infections in susceptible populations. This organism has the ability to persist for extended periods on abiotic surfaces suggesting that these bacteria form biofilms. Recently, the military has seen an increased prevalence of multi-drug resistant Acinetobacter-infections in wounded soldiers returning from Iraq and Afghanistan increasing interest in studying this under-characterized pathogen.
A. baumannii-related projects ongoing in the lab:
A. 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. Studies of defined mutants that can no longer express full-length LPS molecules will yield important insights into the virulence of this opportunistic pathogen.
B. Nosocomial A. baumannii infections have been linked to the fact that A. baumannii colonizes hospital equipment and the organism is able to resist physical and chemical disinfection by forming biofilms. One of the bacterial factors that have been shown to play a role in abiotic surface attachment, persistence and virulence is the polysaccharide poly-N-acetylated glucosamine (PGA), a large extracellular polysaccharide. We have identified a PGA-encoding locus in A. baumannii that shares homology with the previously described pga locus of E. coli, A. pleuropneumoniae, and A. actinomycetemcomitans and the homologous PNAG/PIA-encoding ica locus in S. aureus and S. epidermidis. We are interested in investigating the functional role of the PGA expressed by A. baumannii.
C. We have identified an approximately 26-kb open reading frame in the A. baumannii chromosome that encodes a large outer membrane protein homologous the biofilm-associated protein (Bap) of Staphylococcus aureus. We have produced monoclonal and polyclonal antibodies to the A. baumannii Bap-homologue and generated a transposon mutant defective in Bap expression. Our analyses indicate this protein is expressed on the bacterial surface and is conserved among clinical isolates. Additional studies will focus on the contribution of this molecule to biofilm formation and adherence of A. baumannii to abiotic surfaces.