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Professor Richard W Titball, Biosciences, College of Life and Environmental Sciences, University of Exeter
Burkholderia pseudomallei is the causative agent of melioidosis, a disease of human and animals which is increasingly reported in many tropical and sub-tropical countries. In humans the disease is often fatal despite aggressive antibiotic treatment. Over the past 50 years there has been interest in virulence mechanisms of B. pseudomallei and during the 1950s and 1960s several workers reported that the bacterium produced an exotoxin. However, the identity of this toxin was not determined. We have identified a protein (BPSL1549) which is toxic to mice and to cultured cells. This protein shows structural homology with catalytic domain of E. coli cytotoxic necrotizing factor 1 (CNF1) including conservation of active site catalytic residues. The mutation of one of these residues, cysteine 94, markedly reduced the toxic activity of BPSL1549. The cellular target for B. pseudomallei BPSL1549 was different than that for E. coli CNF1. Whereas CNF1 deamidates Rho GTPases BPSL1549 deamidates eIF4A, blocking translation. The role of BPSL1549 in virulence is still being investigated, this protein may be a target for vaccines and antimicrobials.