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SIP-FKD-SIP finansiert av Fiskeri- og Kystdepartementet

Lysozyme inhibitors; novel drug targets in bacteria

Tildelt: kr 8,5 mill.

Lysozymes are antibacterial enzymes generally acknowledged to play an important role in the innate immune system found in all animals. Recent findings on invertebrate lysozymes as well as on bacterial inhibitors of lysozymes have shed new light on why ver tebrate lysozymes show some restriction in their antibacterial repertoire. Gram-negative bacteria such as Escherichia coli and the Gram-positive bacteria Streptococcus pyrogenes produce their respective proteins that bind and subsequently inhibit the acti on of certain lysozymes. Inactivation or removal of the genes for these inhibitors has been shown to produce bacteria more susceptible to lysozyme killing or with less ability of colonization in the infected host. We propose to suppress the lysozyme inhi bitors by introducing molecules which bind to the inhibitor(s) and thereby reduce or totally block the lysozyme-inhibiting capacities produced by bacteria. Although never previously described, such suppressors are believed to be present in the chemical li brary of the nature, and we intend to search for suppressors in the marine environment, i.e. in invertebrates. In parallel, the known 3-D molecular structure of a complex between lysozyme and a lysozyme inhibitor will form the basis for structure-modellin g and chemical synthesis of additional putative suppressors of lysozyme inhibitors. The final aim is to offer a set of molecules adapted to a novel concept of controlling bacterial growth and infection.


SIP-FKD-SIP finansiert av Fiskeri- og Kystdepartementet