Serotype-Related Variation in Susceptibility to Complement Deposition and Opsonophagocytosis among Clinical Isolates of Streptococcus pneumoniae

Abstract

The polysaccharide capsule is a major virulence factor of Streptococcus pneumoniae; it affects complement resistance and shields the bacterium from phagocytes. Certain capsular serotypes appear to be better able to cause invasive disease than others. Serotypes 1 and 5 are common causes of invasive disease but are rarely isolated from healthy carriers, whereas serotypes 6B and 23F are more frequently isolated from carriage than invasive disease. We have recently shown that serotypes 6B and 19F differ in resistance to complement C3 deposition and opsonophagocytic killing. In this study we assessed the complement resistance and susceptibility to opsonophagocytosis of several other serotypes targeted by the pneumococcal conjugate vaccines. Clinical isolates of serotypes 1, 4, 5, 14, 18C, and 23F were tested along reference strains of corresponding capsular types. The concentration of anticapsular antibodies required for opsonophagocytic killing correlated inversely with C3 deposition on the serotype. Serotype 1 was the most resistant of the clinical isolates to C3 deposition and, along with serotypes 5 and 19F, required the highest concentration of capsule antibodies for opsonophagocytic killing, whereas serotype 23F was the most sensitive to opsonophagocytosis. Sensitivity to C3 deposition and opsonophagocytosis was associated with serotype-specific mortality of invasive pneumococcal disease, suggesting that the primary pathogens, such as serotypes 1 and 5, are more resistant to complement and require a higher concentration of capsule antibodies for opsonophagocytic killing than the opportunistic serotypes such as 6B and 23F, which are associated with a more severe disease outcome.

The Capsular Serotype ofStreptococcus pneumoniaeIs More Important than the Genetic Background for Resistance to Complement

“…However, the exceedingly high estimation of the invasive disease potential of serotype 4 was based on a total of six cases, four of which had the same MLST, 205 (4). Serotype 4 invasive isolates in the previous study (three isolates, two of which MLST 205) were more resistant to complement deposition than serotypes 14 and 23F, whereas the serotype 4 reference strain used in the standard opsonophagocytic assay was significantly more sensitive to complement than the clinical isolates (31). In the present study the serotype 4 TIGR4 strain was inferior to all other capsule-switched mutants.…”

“…We have previously found that pneumococcal isolates of certain serotypes, such as 1 and 5, associated with invasive disease were particularly resistant to complement deposition and opsonophagocytic killing, while serotypes such as 6B and 23F, associated with carriage, were more sensitive to deposition of C3 and opsonophagocytosis (30,31). We found significant variation in the magnitude of complement deposition between isolates expressing the same capsular serotype, suggesting a role of serotype-independent factors in the outcome of this particular interaction.…”

“…In our previous study we found that the invasiveness of certain serotypes could be associated with increased resistance to complement deposition and opsonophagocytic killing (31). Analysis of several capsule-switched mutants in the present study indicates that exchange of the capsule can directly alter the resistance of the strain to complement and opsonophagocytosis.…”

“…Another reason why the clinical isolates are more resistant could be that the genetic background of the isolates is adapted to a particular serotype. In our previous study we found that serotype 5 clinical isolates were relatively resistant to complement and required a high concentration of polysaccharide-specific antibodies for opsonophagocytic killing (31). The serotype 5 capsuleswitched mutants of the present study, prepared in the genetic backgrounds of TIGR4 and 603, were less resistant to complement in comparison with many other serotypes expressed in the same genetic background.…”

RrgB321, a Fusion Protein of the Three Variants of the Pneumococcal Pilus Backbone RrgB, Is ProtectiveIn Vivoand Elicits Opsonic Antibodies

“…Published studies report how the characteristic of the capsule of S. pneumoniae strains can affect the site and quantity of complement deposition (19,40,42), and this could account for the different responses to in vitro killing obtained here. Furthermore, a variable concentration of capsular polysaccharide-specific antibodies is required to obtain similar OPKA levels, suggesting that these antibodies could also have different functional properties (24,25). In light of this, we cannot exclude the possibility that the different OPKA results observed for the three pilus-positive strains could be due to different functionalities of the antibodies directed against the three variants constituting the fusion protein.…”