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A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A

Author

Abimael Cruz, Guillaume M. Hautbergue, Peter J. Artymiuk, Patrick J. Baker, Monika Bokori-Brown, Chung-Te Chang, Mark J. Dickman, Angela Essex-Lopresti, Sarah V. Harding, Nor Muhammad Mahadi, Laura E. Marshall, Rahmah Mohamed, Sheila Nathan, Sarah A. Ngugi, Catherine Ong, Wen Fong Ooi, Lynda J. Partridge, Helen L. Phillips,M. Firdaus Raih, Sergei Ruzhenikov, Mitali Sarkar-Tyson, Svetlana E. Sedelnikova, Sophie J. Smither, Patrick Tan, Richard W. Titball, Stuart A. Wilson, David W. Rice

The structure of BPSL1549, a protein of unknown function from Burkholderia pseudomallei reveals a similarity to E. coli cytotoxic necrotizing factor 1. We found that BPSL1549 acted as a potent cytotoxin against eukaryotic cells and was lethal when administered to mice. Expression levels of bpsl1549 correlate with conditions expected to promote or suppress pathogenicity. BPSL1549 promotes deamidation of Gln of the translation initiation factor eIF4A, abolishing its helicase activity and inhibiting translation. We propose to name BPSL1549 Burkholderia Lethal Factor 1 (BLF1).