Sialic Acid metabolism and systemic pasteurellosis.
Pasteurella multocida subsp. multocida is a commensal and opportunistic pathogen of food animals, wildlife, and pets and a zoonotic cause of human infection arising from contacts with these animals. Here, an investigation of multiple serotype A strains demonstrated the occurrence of membrane sialyltransferase. Although P. multocida lacks the genes for the two earliest steps in de novo sialic acid synthesis, adding sialic acid to the growth medium resulted in uptake, activation, and subsequent transfer of sialic acid to a membrane acceptor resembling lipooligosaccharide. Two candidate-activating enzymes with homology to Escherichia coli cytidine 5'-monophospho-N-acetylneuraminate synthetase were overproduced as histidine-tagged polypeptides. The synthetase encoded by pm0187 was at least 37 times more active than the pm1710 gene product, suggesting pm0187 encodes the primary sialic acid cytidylyltransferase in P. multocida. A sialate aldolase (pm1715) mutant unable to initiate dissimilation of internalized sialic acid was not attenuated in the CD-1 mouse model of systemic pasteurellosis, indicating that the nutritional function of sialate catabolism is not required for systemic disease. In contrast, the attenuation of a sialate uptake-deficient mutant supports the essential role in pathogenesis of a sialylation mechanism that is dependent on an environmental (host) supply of sialic acid. The combined results provide the first direct evidence of sialylation by a precursor scavenging mechanism in pasteurellae and of a potential tripartite ATP-independent periplasmic sialate transporter in any species.
Steenbergen
Susan M
SM
Laboratory of Sialobiology, Department of Pathobiology, Universityof Illinois at Urbana-Champaign, Urbana, IL 61802, USA.
Lichtensteiger
Carol A
CA
Caughlan
Ruth
R
Garfinkle
Jackie
J
Fuller
Troy E
TE
Vimr
Eric R
ER
D000818:Animals; D021461:Animals, Outbred Strains; D002417:Cattle; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D016366:Open Reading Frames / Q000235:genetics; D010326:Pasteurella Infections / Q000378:metabolism* / Q000382:microbiology; D016979:Pasteurella multocida / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D012794:Sialic Acids / Q000378:metabolism*; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
D012794:Sialic Acids; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid; D012799:Sialyltransferases; D005634:Fructose-Bisphosphate Aldolase
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