Natural selection in the chicken host identifies 3-deoxy-D-manno-octulosonic acid kinase residues essential for phosphorylation of Pasteurella multocida lipopolysaccharide

Harper, Marina, Cox, Andrew D., St. Michael, Frank, Ford, Mark, Wilkie, Ian W., Adler, Ben and Boyce, John D. (2010) Natural selection in the chicken host identifies 3-deoxy-D-manno-octulosonic acid kinase residues essential for phosphorylation of Pasteurella multocida lipopolysaccharide. Infection and Immunity, 78 9: 3669-3677. doi:10.1128/IAI.00457-10

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Author Harper, Marina
Cox, Andrew D.
St. Michael, Frank
Ford, Mark
Wilkie, Ian W.
Adler, Ben
Boyce, John D.
Title Natural selection in the chicken host identifies 3-deoxy-D-manno-octulosonic acid kinase residues essential for phosphorylation of Pasteurella multocida lipopolysaccharide
Formatted title
Natural selection in the chicken host identifies 3-deoxy-D-manno-octulosonic acid kinase residues essential for phosphorylation of Pasteurella multocida lipopolysaccharide
Journal name Infection and Immunity   Check publisher's open access policy
ISSN 1098-5522
1070-6313
Publication date 2010-09
Sub-type Article (original research)
DOI 10.1128/IAI.00457-10
Open Access Status File (Publisher version)
Volume 78
Issue 9
Start page 3669
End page 3677
Total pages 9
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2011
Language eng
Formatted abstract
Pasteurella multocida is the causative agent of a number of diseases in animals, including fowl cholera.
P. multocida strains simultaneously express two lipopolysaccharide (LPS) glycoforms (glycoforms A and
B) that differ only in their inner core structure. Glycoform A contains a single 3-deoxy-D-manno-octulosonic
acid (Kdo) residue that is phosphorylated by the Kdo kinase, KdkA, whereas glycoform B contains
two unphosphorylated Kdo residues. We have previously shown that P. multocida mutants lacking the
heptosyltransferase, HptA, produce full-length glycoform B LPS and a large amount of truncated glycoform
A LPS, as they cannot add heptose to the glycoform A inner core. These hptA mutants were attenuated
in chickens because the truncated LPS made them vulnerable to host defense mechanisms, including
antimicrobial peptides. However, here we show that birds inoculated with high doses of the hptA mutant
developed fowl cholera and the P. multocida isolates recovered from diseased birds no longer expressed
truncated LPS. Sequencing analysis revealed that the in vivo-derived isolates had mutations in kdkA,
thereby suppressing the production of glycoform A LPS. Interestingly, a number of the spontaneous KdkA
mutant strains produced KdkA with a single amino acid substitution (A112V, R123P, H168Y, or D193N).
LPS structural analysis showed that complementation of a P. multocida kdkA mutant with wild-type kdkA
restored expression of glycoform A to wild-type levels, whereas complementation with any of the mutated
kdkA genes did not. We conclude that in P. multocida KdkA, the amino acids A112, R123, H168, and D193
are critical for Kdo kinase function and therefore for glycoform A LPS assembly. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Keyword Dependent protein-kinase
Structural-analysis
Catalynic subunit
Heptosyltranferase mutant
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Veterinary Science Publications
 
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Created: Sun, 05 Sep 2010, 00:06:01 EST