Protective Role of the Capsule and Impact of Serotype 4 Switching on Streptococcus mitis

Abstract

eThe polysaccharide capsule surrounding Streptococcus pneumoniae is essential for virulence. Recently, Streptococcus mitis, a human commensal and a close relative of S. pneumoniae, was also shown to have a capsule. In this study, the S. mitis type strain switched capsule by acquisition of the serotype 4 capsule locus of S. pneumoniae TIGR4, following induction of competence for natural transformation. Comparison of the wild type with the capsule-switching mutant and with a capsule deletion mutant showed that the capsule protected S. mitis against phagocytosis by RAW 264.7 macrophages. This effect was enhanced in the S. mitis strain expressing the S. pneumoniae capsule, which showed, in addition, increased resistance against early clearance in a mouse model of lung infection. Expression of both capsules also favored survival in human blood, and the effect was again more pronounced for the capsule-switching mutant. S. mitis survival in horse blood or in a mouse model of bacteremia was not significantly different between the wild type and the mutant strains. In all models, S. pneumoniae TIGR4 showed higher rates of survival than the S. mitis type strain or the capsule-switching mutant, except in the lung model, in which significant differences between S. pneumoniae TIGR4 and the capsule-switching mutant were not observed. Thus, we identified conditions that showed a protective function for the capsule in S. mitis. Under such conditions, S. mitis resistance to clearance could be enhanced by capsule switching to serotype 4, but it was enhanced to levels lower than those for the virulent strain S. pneumoniae TIGR4.

Capsular Polysaccharide Expression in CommensalStreptococcusSpecies: Genetic and Antigenic Similarities to Streptococcus pneumoniae

“…Different polysaccharides have been described for selected strains of S. oralis and S. mitis (16, 17), but their structural variation within the species has not been examined systematically (33). Interestingly, serological cross-reactions between pneumococci and other streptococci of uncertain identity were observed in the past (34–37).…”

Investigating the biomechanical properties of streptococcal polysaccharide capsules using atomic force microscopy

“…TEM demonstrated that, compared to the wild type S. mitis strain (Fig. 1c), which we have previously shown expresses a capsule with no known S. pneumoniae serotype homologue (Rukke et al, 2014), the S. mitis TIGR4 cps strain had a more obvious and relatively thick capsule layer (Fig. 1b) similar to the capsule layer seen with S. pneumoniae TIGR4 (Fig.…”

“…We have previously shown expression of the TIGR4 S. pneumoniae serotype 4 capsule fails to make the S. mitis SK142 strain virulent in mice (Rukke et al, 2014). To assess whether there were major morphological changes in the capsule expressed by S. pneumoniae TIGR4 and S. mitis TIGR4 cps strains, we utilised a TEM method that preserves the capsular polysaccharide to visualise and measure the depth of the capsule, whilst also observing the density and arrangement of the surface sugars.…”

“…Expression of the S. pneumoniae serotype 4 capsule by S. mitis reduced its sensitivity to macrophage-mediated phagocytosis (Rukke et al, 2014). To extend these data and characterise whether the serotype 4 capsule improves S. mitis immune evasion we used an established flow cytometry assay of neutrophil opsonophagocytosis using freshly isolated human neutrophils (Brown et al, 2002, Hyams et al, 2010b).…”

The Regulatory Role of the Oral Commensal Streptococcus mitis on Human Monocytes

“…Streptococcus mitis is one of the earliest commensal colonizers of the human oral cavity and resides in the oral mucosa from early infancy and throughout life. In immunocompetent persons, S. mitis is rarely associated with disease as it survives poorly in blood and is immediately cleared . In immunocompromised patients, however, it is the oral commensal streptococcal species that is most frequently associated with endocarditis or septicemia .…”