Role of Pneumococcal NanA Neuraminidase Activity in Peripheral Blood

Abstract

The most frequent form of hemolytic-uremic syndrome (HUS) is associated with infections caused by Shiga-like toxin-producing Enterohaemorrhagic Escherichia coli (STEC). In rarer cases HUS can be triggered by Streptococcus pneumoniae . While production of Shiga-like toxins explains STEC-HUS, the mechanisms of pneumococcal HUS are less well-known . S. pneumoniae produces neuraminidases with activity against cell surface sialic acids that are critical for factor H-mediated complement regulation on cells and platelets. The aim of this study was to find out whether S. pneumoniae neuraminidase NanA could trigger complement activation and hemolysis in whole blood. We studied clinical S. pneumoniae isolates and two laboratory strains, a wild-type strain expressing NanA, and a NanA deletion mutant for their ability to remove sialic acids from various human cells and platelets. Red blood cell lysis and activation of complement was measured ex vivo by incubating whole blood with bacterial culture supernatants. We show here that NanA expressing S. pneumoniae strains and isolates are able to remove sialic acids from cells, and platelets. Removal of sialic acids by NanA increased complement activity in whole blood, while absence of NanA blocked complement triggering and hemolytic activity indicating that removal of sialic acids by NanA could potentially trigger pHUS.

A Transcriptional Activator of Ascorbic Acid Transport in Streptococcus pneumoniae Is Required for Optimal Growth in Endophthalmitis in a Strain-Dependent Manner

“…Additional time points could reveal information regarding fitness in the vitreous humor that was not captured previously. We were also unable to create complemented strains of the mutants; many S. pneumoniae studies testing isogenic mutations appear to lack complemented strains [29,30,31,32,33]. Nevertheless, our mutants were generated in frame and were verified by sequencing to be located in the correct position.…”

Crosstalk Between Platelets and Microbial Pathogens

“…Scavenging of host sialic residues by microbial pathogens increases immune evasion and assists in survival and dissemination (125,126). Direct cleavage of platelet sialic residues by pathogen-derived neuraminidase has been reported in bacterial, and parasitic infections (127). Indirectly, pathogens could induce platelet desialylation mediated by platelet-derived neuraminidase, as was reported with dengue virus infection (128).…”

Media Matters, Examining Historical and Modern Streptococcus pneumoniae Growth Media and the Experiments They Affect

“…Consistent with previous reports, genes associated with adhesion and colonization (e.g., neuraminidase and choline binding proteins) were downregulated during blood agar cultivation ( Gosink et al., 2000 ; Brittan et al., 2012 ). While neuraminidase and choline binding proteins support bacterial colonization and dissemination respectively, neuraminidase cleaves sialic acids in the blood which recruits host complement ( Attali et al., 2008 ; Syed et al., 2019 ).…”