Sialic Acid metabolism and systemic pasteurellosis

Area of Science:

• Microbiology
• Bacteriology
• Pathogenesis

Background:

• Pasteurella multocida subsp. multocida is a significant pathogen in animals and a zoonotic agent in humans.
• This bacterium lacks genes for de novo sialic acid synthesis, suggesting reliance on external sialic acid sources.

Purpose of the Study:

• To investigate the mechanism of sialic acid utilization and its role in P. multocida pathogenesis.
• To identify and characterize enzymes involved in sialic acid uptake, activation, and transfer.

Main Methods:

• Investigated membrane sialyltransferase activity in serotype A strains.
• Overproduced and characterized candidate sialic acid-activating enzymes (pm0187 and pm1710).
• Generated and tested a sialate aldolase (pm1715) mutant and a sialate uptake-deficient mutant in a mouse model.

Main Results:

• Sialic acid from the growth medium was efficiently taken up, activated, and transferred to lipooligosaccharide-like acceptors.
• The pm0187 gene product showed significantly higher cytidylyltransferase activity compared to pm1710.
• A sialate uptake mutant was attenuated, while a sialate aldolase mutant was not, indicating sialic acid scavenging is vital for virulence.

Conclusions:

• P. multocida utilizes a precursor scavenging mechanism for sialylation, dependent on host-derived sialic acid.
• Identified pm0187 as the primary sialic acid cytidylyltransferase.
• Demonstrated the essential role of sialic acid uptake in systemic pasteurellosis and proposed a novel sialate transporter system.