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Infection and Immunity, December 1998, p. 5636-5642, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Activity of the Mitogenic Pasteurella multocida Toxin Requires an Essential C-Terminal Residue

Philip N. Ward,1 Antony J. Miles,1 Ian G. Sumner,2 Lewis H. Thomas,1 and Alistair J. Lax3,*

Institute for Animal Health, Compton Laboratory, Compton, Newbury, Berkshire, RG20 7NN,1 Institute of Food Research, Reading, Berkshire, RG6 2EF,2 and Oral Microbiology, Guy's, King's and St. Thomas' Dental Institute, Guy's Hospital, London, SE1 9RT,3 United Kingdom

Received 11 June 1998/Returned for modification 24 July 1998/Accepted 17 September 1998

Pasteurella multocida toxin (PMT) is a potent mitogen that also affects bone resorption. PMT acts intracellularly and is therefore postulated to have several domains involved in different aspects of its function. The toxin contains eight cysteine residues. Mutants with individual substitutions for each of these residues were constructed, and the effects of these on the biological activity of the toxin were determined by cultured-cell assays. Only the most C-terminal of the eight cysteines (C1165) was essential for full activity, although mutation of the cysteine residue at position 1159 caused a slight but reproducible loss of potency. In animal challenge experiments, mutant toxin (C1165S) was not toxic to piglets, even at doses exceeding a lethal dose of active PMT 1,000-fold. The mutant and wild-type toxins displayed identical purification characteristics, similar susceptibility to proteolytic digestion, and circular dichroism profiles, which indicated that no gross structural changes had taken place. The function of the essential C1165 residue is not yet known, although its most likely role is an enzymatic one at or near the catalytic center of the toxin.

* Corresponding author. Mailing address: Oral Microbiology, Guy's, King's and St. Thomas' Dental Institute, Floor 28, Guy's Hospital, London, SE1 9RT, United Kingdom. Phone: 44 (0) 171 955 2848. Fax: 44 (0) 171 955 2847. E-mail: a.lax{at}umds.ac.uk.

Infection and Immunity, December 1998, p. 5636-5642, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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