Sialic Acid Metabolism and Systemic Pasteurellosis

Abstract

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.

The VC1777–VC1779 proteins are members of a sialic acid-specific subfamily of TRAP transporters (SiaPQM) and constitute the sole route of sialic acid uptake in the human pathogen Vibrio cholerae

“…4). There is also strong genetic evidence that the pm1708-pm1709-encoded TRAP transporter from P. multocida is also involved in uptake of Neu5Ac (Steenbergen et al, 2005) (Fig. 4).…”

“…Sialic acids are also utilized by commensal and pathogenic bacteria in a number of ways; for example, several pathogenic species of bacteria have been shown to sialylate their cell surfaces to mask them from the host immune system (Varki, 1992(Varki, , 2008Vimr & Lichtensteiger, 2002;Vimr et al, 2004). Many bacteria, including Vibrio cholerae, are also able to utilize sialic acid as a sole carbon, nitrogen and energy source (Nees et al, 1976;Vimr & Troy, 1985;Chang et al, 2004;Severi et al, 2005;Steenbergen et al, 2005;Almagro-Moreno & Boyd, 2009a, b;Brigham et al, 2009). Vimr and colleagues showed that three key catabolic enzymes, (i) Neu5Ac lyase/aldolase (NanA), (ii) N-acetylmannosamine kinase (NanK) and (iii) ManNAc-6-phosphate epimerase (NanE), act sequentially to convert sialic acid (Neu5Ac) into N-acetylglucosamine 6-phosphate (GlcNAc-6-P) (Vimr & Troy, 1985;Vimr et al, 2004).…”

“…The TRAP transporter (SiaPQM or SiaPT) associated with the SAC gene cluster in H. influenzae has been shown to be highly efficient in the uptake of sialic acid (Allen et al, 2005;Severi et al, 2005;Müller et al, 2006;Mulligan et al, 2009). Likewise, in Pasteurella multocida, SiaP (PM1709) is essential for sialic acid transport (Steenbergen et al, 2005). Vibrio vulnificus clinical strains contain genetically linked sialic acid transport and catabolism gene clusters identical to those of V. cholerae (Almagro-Moreno & Boyd, 2009a;Jeong et al, 2009).…”

Pasteurella multocida sialic acid aldolase: a promising biocatalyst

“…NanA activity has been found in Pasteurella multocida (Drzeniek et al 1972) and a hypothetic gene sequence encoding NanA (Pm1715, GenBank accession no. Q9CKB0) has been identified (Steenbergen et al 2005). Previously, we reported the cloning of a NanA from E. coli K-12 substrain MG1655 (EcNanA) (Yu et al 2004).…”

An Orthologue of Bacteroides fragilis NanH Is the Principal Sialidase in Tannerella forsythia

“…The sialic acid residues contribute to a range of important biological functions, including cellular interactions and stabilizing the conformation of glycoproteins and cellular membranes; these residues also expose or mask receptors for ligands, antibodies, or enzymes and contribute to the function and stability of glycoproteins in serum (3,40). Sialidases are implicated in the pathogenicity of some bacteria, including Clostridium perfringens (33), Streptococcus pneumoniae (46), Pasteurella multocida (42), and Pseudomonas aeruginosa (41). They can modify the host's ability to respond to bacterial infection by increasing the susceptibility of immunoglobulin molecules to proteolytic degradation (28).…”