Long considered a harmless commensal of the human respiratory tract, the gram-negative bacterium Moraxella catarrhalis has recently emerged as a significant cause of infectious diseases. These infections are a significant health problem, medically as well as economically, and addressing these issues is complicated by the fact that little is known about pathogenesis by M. catarrhalis. Our long-term objectives are to study the molecular basis for M. catarrhalis adherence to its human host, and to evaluate the potential of interfering with this adherence as a strategy to reduce the risks of infections. We have already isolated E. coli recombinant clones that gained the ability to bind to human cells by virtue of expressing new M. catarrhalis adhesin genes. Furthermore, we have also isolated fourteen M. catarrhalis transposon mutants that are substantially reduced in their ability to bind to human lung cells.
The Specific Aims of the Proposed Research Plan are: 1. To identify and characterize the genes encoding new M. catarrhalis adhesins for human cells. 2. To evaluate the vaccinogenic potential of these new M. catarrhalis adhesins. 3. To identify M. catarrhalis gene products involved in the expression as well as surface display of adhesins ? We will use recombinant DNA techniques as well as transposon mutagenesis to identify genes that are involved in the binding of M. catarrhalis to human cells. We will determine the nucleotide sequence of candidate genes and characterize their encoded products. We will also use recombinant forms of new M. catarrhalis adhesins to determine whether they elicit the production of biologically relevant antibodies. Our studies will have direct applications in vaccine as well as antimicrobial development. ? ? ?
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