Role of Pneumococcal NanA Neuraminidase Activity in Peripheral Blood.

Shahan Syed,Karita Haapasalo,Pipsa Hakala,Helena A K Lapatto,Anirudh K Singh,T Sakari Jokiranta,Samantha J King,Seppo Meri

doi:10.3389/fcimb.2019.00218

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.

Highlights

Streptococcus pneumoniae infection is a major cause of morbidity and mortality worldwide
The presence of sialic acids was detected by using NT647labeled Maackia Amurensis Lectin II (MAL-II) that recognizes α-2-3 linked terminal sialic acids
Pneumococcal neuraminidase activity has been suggested to trigger Pneumococcal atypical hemolytic uremic syndrome (pHUS) (Coats et al, 2011) but it is unclear whether expression of neuraminidase correlate with hemolytic-uremic syndrome (HUS) disease pathology (Janapatla et al, 2013; Smith et al, 2013; Singh et al, 2016)

Summary

Introduction

Streptococcus pneumoniae infection is a major cause of morbidity and mortality worldwide. Despite the current vaccination program it kills approximately half a million children under 5 years of age worldwide every year. It typically causes diseases such as otitis media, pneumonia, bacteremia, and meningitis. S. pneumoniae is known to express neuraminidases, NanA, NanB, and NanC that can remove sialic acids from cell surfaces (Burnaugh et al, 2008). Removal of sialic acids from cell membrane glycostructures reduces binding of complement regulator factor H to self-cell surfaces (Nissila et al, 2018).

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