Streptococcus pneumoniae PspC Subgroup Prevalence in Invasive Disease and Differences in Contribution to Complement Evasion

Abstract

The pneumococcal capsular serotype is an important determinant of complement resistance and invasive disease potential, but other virulence factors have also been found to contribute. Pneumococcal surface protein C (PspC), a highly variable virulence protein that binds complement factor H to evade C3 opsonization, is divided into two subgroups: choline-bound subgroup I and LPxTG-anchored subgroup II. The prevalence of different PspC subgroups in invasive pneumococcal disease (IPD) and functional differences in complement evasion are unknown. The prevalence of PspC subgroups in IPD isolates was determined in a collection of 349 sequenced strains of isolated from adult patients. deletion mutants and isogenic switch mutants were constructed to study differences in factor H binding and complement evasion in relation to capsule thickness. Subgroup I was far more prevalent in IPD isolates than subgroup II The presence of capsule was associated with a greater ability of bound factor H to reduce complement opsonization. Pneumococcal subgroup I PspC bound significantly more factor H and showed more effective complement evasion than subgroup II PspC in isogenic encapsulated pneumococci. We conclude that variation in the PspC subgroups, independent of capsule serotypes, affects pneumococcal factor H binding and its ability to evade complement deposition.

Oestrogen promotes innate immune evasion ofCandida albicansthrough inactivation of the alternative complement system

“…Increased deposition of complement is normally associated with increased phagocytosis. However, processing of C3 can be inhibited by the recruitment of host regulatory proteins like Factor H, and several pathogens are known to avoid opsonophagocytosis through enhanced recruitment of Factor H [38, 39]. Therefore, the ability of oestrogen adapted C. albicans cells to bind Factor H was quantified.…”

Same, Same, but Different: Molecular Analyses ofStreptococcus pneumoniaeImmune Evasion Proteins Identifies new Domains and Reveals Structural Differences between PspC and Hic Variants

“…When comparing prevalence and distribution of PspC vs. Hic variants among 349 clinical S. pneumoniae isolates derived from adult patients with invasive pneumococcal disease, 298 isolates (85.4%) encoded a PspC-variant, 22 strains (6.3%) a Hic-variant, 19 isolates (5.4%) had a pspC and hic genes and only 10 isolates (2.9%) had neither pspC nor hic genes (61). In addition, invasive, PspC expressing strains bound more Factor H, and Factor H binding and immune control was more effective in encapsulated as compared to unencapsulated strains.…”

Joint Sequencing of Human and Pathogen Genomes Reveals the Genetics of Pneumococcal Meningitis

“…Three patients had clear bone destruction and/or pneumocephalus and one patient had a skull defect due to previous surgery. We further tested whether the two major forms of PspC were associated with meningitis, as has previously been suggested 32 , but did not find either to be overrepresented, when accounting for population structure. dacB is involved in preserving cell wall shape and has shown to attenuate virulence in a mouse model of lung infection 28 .…”