Enhanced phagocytosis and complement-mediated killing of Mannheimia haemolytica serotype 1 following in-frame CMP-sialic acid synthetase (neuA) gene deletion

Microbiol Spectr. 2023 Dec 12;11(6):e0294423. doi: 10.1128/spectrum.02944-23. Epub 2023 Oct 18.

Abstract

The Gram-negative coccobacillus Mannheimia haemolytica is a natural inhabitant of the upper respiratory tract in ruminants and the most common bacterial agent involved in bovine respiratory disease complex development. Key virulence factors harbored by M. haemolytica are leukotoxin, lipopolysaccharide, capsule, adhesins, and neuraminidase which are involved in evading innate and adaptive immune responses. In this study, we have shown that CMP-sialic acid synthetase (neuA) is necessary for the incorporation of sialic acid onto the membrane, and inactivation of neuA results in increased phagocytosis and complement-mediated killing of M. haemolytica, thus demonstrating that sialylation contributes to the virulence of M. haemolytica.

Keywords: CMP-N-acetylneuraminic acid (Neu5Ac/sialic) synthetase; M. haemolytica; complement-mediated killing; phagocytosis; reactive oxygen species; sialic acid.

MeSH terms

  • Animals
  • Cattle
  • Gene Deletion
  • Mannheimia haemolytica* / genetics
  • Mannheimia haemolytica* / metabolism
  • N-Acylneuraminate Cytidylyltransferase / genetics
  • N-Acylneuraminate Cytidylyltransferase / metabolism
  • Phagocytosis
  • Serogroup

Substances

  • N-Acylneuraminate Cytidylyltransferase