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The pnhA Gene of Pasteurella multocida Encodes a Dinucleoside Oligophosphate Pyrophosphatase Member of the Nudix Hydrolase Superfamily

Tonia Urick,^1, Chien I-Chang,^1, Ellen Arena,¹ WenLian Xu,² Maurice J. Bessman,² and Carmel G. Ruffolo^1*

Department of Biological Sciences, University of Wisconsin—Parkside, Kenosha, Wisconsin,¹ Department of Biology and The McCollum-Pratt Institute, The Johns Hopkins University, Baltimore, Maryland²

Received 10 November 2004/ Accepted 31 March 2005

The pnhA gene of Pasteurella multocida encodes PnhA, which is a member of the Nudix hydrolase subfamily of dinucleoside oligophosphate pyrophosphatases. PnhA hydrolyzes diadenosine tetra-, penta-, and hexaphosphates with a preference for diadenosine pentaphosphate, from which it forms ATP and ADP. PnhA requires a divalent metal cation, Mg²⁺ or Mn²⁺, and prefers an alkaline pH of 8 for optimal activity. A P. multocida strain that lacked a functional pnhA gene, ACP13, was constructed to further characterize the function of PnhA. The cellular size of ACP13 was found to be 60% less than that of wild-type P. multocida, but the growth rate of ACP13 and its sensitivity to heat shock conditions were similar to those of the wild type, and the wild-type cell size was restored in the presence of a functional pnhA gene. Wild-type and ACP13 strains were tested for virulence by using the chicken embryo lethality model, and ACP13 was found to be up to 1,000-fold less virulent than the wild-type strain. This is the first study to use an animal model in assessing the virulence of a bacterial strain that lacked a dinucleoside oligophosphate pyrophosphatase and suggests that the pyrophosphatase PnhA, catalyzing the hydrolysis of diadenosine pentaphosphates, may also play a role in facilitating P. multocida pathogenicity in the host.

Present address: Division of Communicable Diseases and Immunology, Department of Enterics, Walter Reed Army Institute of Research, Silver Spring, MD 20910.

Present address: Department of Biomedical Sciences, University of Massachusetts Medical School, Worcester, MA 01655.