Gene Acquisition by a Distinct Phyletic Group within Streptococcus pneumoniae Promotes Adhesion to the Ocular Epithelium

Abstract

Changes in the gene content of pathogens can modify their ability to colonize and/or survive in different body sites in the human host. In this study, we investigate a gene acquisition event and its role in the pathogenesis of Streptococccus pneumoniae (pneumococcus). Our findings suggest that the gene encoding the predicted surface protein SspB has been transferred from Streptococcus suis (a distantly related streptococcal species) into a distinct set of pneumococcal strains. This group of strains distinguishes itself from the remainder of pneumococcal strains by extensive differences in genomic composition and by the ability to cause conjunctivitis. We find that the presence of sspB increases adherence of pneumococcus to the ocular epithelium. Thus, our data support the hypothesis that a subset of pneumococcal strains has gained genes from neighboring species that enhance their ability to colonize the epithelium of the eye, thus expanding into a new niche.

The Best of All Worlds: Streptococcus pneumoniae Conjunctivitis through the Lens of Community Ecology and Microbial Biogeography

“…Recent comparative genomic analyses now allow us to characterize these NESp strains into two groups based on alterations in their capsular polysaccharide synthesis (cps) loci: group I NESp, which contains mutationally defunct or absent cps genes; and group II NESp, where these cps genes are replaced almost entirely by novel gene content [87,105]. The latter group contains a distinct phyletic cluster of mostly nonencapsulated S. pneumoniae with an almost exclusive proclivity for causing epidemic conjunctivitis [10,[106][107][108]. If one basic assumption of all evolutionary biology is that genetic change is driven mostly by the underlying pursuit for survival, then the loss of encapsulation and the acquisition of virulence factors in this rogue clade must also confer a basic survival advantage within a new environmental niche.…”

“…This reflects the influence of the capsule in defining the environment in which surface features occur on encapsulated strains, and novel selective pressures occur in its absence. Much of the novel genomic content in ECC strains appears to have been donated by unencapsulated oral streptococci [10,106,139]. Novel cell wall proteins, encoded by novel genes found at the cps locus, allow ECC strains to overcome or evade the robust suite of physical and chemical protections that characterize the conjunctival microenvironment.…”

“…Novel cell wall proteins, encoded by novel genes found at the cps locus, allow ECC strains to overcome or evade the robust suite of physical and chemical protections that characterize the conjunctival microenvironment. These include: the oligopeptide binding proteins AliC and AliD (encoded by AliC and AliD, respectively) [10,98], which may enhance mucosal colonization by conferring resistance to leukocyte cytotoxicity and complement deposition [98]; the choline binding protein A (CbpA) variants CbpAC1 and CbpAC2, which among other functions may be involved in binding to the secretory component of IgA [10] and also in preventing complement deposition [98]; surface exposed adhesins (SspBC1/SspBC2), which may be important in cell agglutination and conjunctival epithelial adhesion [10,106]; the neuraminidases (NanO1/NanO2) [10], which putatively cleave sialic acids on the surface of mucosal glycans and mucins [140]; and zinc metalloprotease C (zmpC1/zmpC2) [10], which reportedly cleaves the ectodomain portion of the membrane-bound mucin MUC16, thereby exposing the underlying epithelial cell to infection [10,141].…”

“…Many non-ECC unencapsulated strains are phylogenetically grouped with the majority of pneumococcal strains, and conversely, some encapsulated strains are capable of causing sporadic conjunctivitis. As a distinct cluster of NESp, ECC lineages are particularly well adapted specifically for conjunctival colonization and infection [10,106], most likely by virtue of their novel gene content. These adaptations do not appear to extend to isolates which invade other ocular sites: sequencing data from our laboratory (unpublished) and that of Antic and colleagues [106], suggest that clinical isolates of S. pneumoniae from keratitis and endophthalmitis (aqueous/vitreous) are clustered within the major phyletic group.…”

“…Having established that NESp follow cosmopolitan distributions worldwide, what can be made of colonization and dispersion dynamics within individual hosts? Comparative genomic analyses demonstrating the genomic equivalence of nasopharyngeal and conjunctival ECC isolates suggest that nasopharyngeal colonization is likely to precede conjunctival infection, favoring the hypothesis that ECC strains migrate freely between both host compartments [10,106]. This lack of evidence for a distance-decay relationship-which classically suggests that populations should become increasingly diversified with increasing physical displacement from its reservoir [143,144]-raises several questions regarding how these ECC strains have evolved to be able to physically straddle these two disparate biogeographies.…”