Pneumococcal serotype determines growth and capsule size in human cerebrospinal fluid

Annelies Müller,Anne Von Gottberg,Lucy J Hathaway,Linda De Gouveia,Anke Salmen,Suzanne Aebi

doi:10.1186/s12866-020-1700-7

Abstract

BackgroundThe polysaccharide capsule is a major virulence factor of S. pneumoniae in diseases such as meningitis. While some capsular serotypes are more often found in invasive disease, high case fatality rates are associated with those serotypes more commonly found in asymptomatic colonization. We tested whether growth patterns and capsule size in human cerebrospinal fluid depends on serotype using a clinical isolate of S. pneumoniae and its capsule switch mutants.ResultsWe found that the growth pattern differed markedly from that in culture medium by lacking the exponential and lysis phases. Growth in human cerebrospinal fluid was reduced when strains lost their capsules. When a capsule was present, growth was serotype-specific: high carriage serotypes (6B, 9 V, 19F and 23F) grew better than low carriage serotypes (7F, 14, 15B/C and 18C). Growth correlated with the case-fatality rates of serotypes reported in the literature. Capsule size in human cerebrospinal fluid also depended on serotype.ConclusionsWe propose that serotype-specific differences in disease severity observed in meningitis patients may, at least in part, be explained by differences in growth and capsule size in human cerebrospinal fluid. This information could be useful to guide future vaccine design.

Highlights

The polysaccharide capsule is a major virulence factor of S. pneumoniae in diseases such as meningitis
The growth pattern of S. pneumoniae in human CSF (hCSF) differs from that in culture medium To determine whether S. pneumoniae is able to grow and how it behaves in hCSF in vitro, we performed growth analysis over 40 h of the strain 106.66 in brain heart infusion (BHI) + fetal calf serum (FCS) and hCSF
To test whether this pattern of growth was due to limited nutrition, the bacteria were grown in Chemically-defined medium (CDM)

Summary

Introduction

The polysaccharide capsule is a major virulence factor of S. pneumoniae in diseases such as meningitis. While some capsular serotypes are more often found in invasive disease, high case fatality rates are associated with those serotypes more commonly found in asymptomatic colonization. Invasive pneumococcal disease (IPD) includes the life-threatening conditions of bacteraemia and meningitis, both of which have high mortality rates [1, 2] and S. pneumoniae is a leading cause of pneumonia. A major virulence factor of S. pneumoniae is the polysaccharide capsule and, based on the biochemical properties of the capsule, S. pneumoniae is categorized into different serotypes. Several serotypes (including 7F, 14, 15B/C and 18C) have repeatedly been associated with invasive disease while other serotypes (such as 6B, 9 V, 19F and 23F) are more commonly associated with asymptomatic colonization of the human nasopharynx [1, 4,5,6,7].

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