Abstract
Streptococcus pneumoniae and Streptococcus mitis are genetically closely related and both frequently colonise the naso-oropharynx, yet S. pneumoniae is a common cause of invasive infections whereas S. mitis is only weakly pathogenic. We hypothesise that sensitivity to innate immunity may underlie these differences in virulence phenotype. We compared the sensitivity of S. pneumoniae and S. mitis strains to complement-mediated immunity, demonstrating S. mitis strains were susceptible to complement-mediated opsonophagocytosis. S. pneumoniae resistance to complement is partially dependent on binding of the complement regulator Factor H by the surface protein PspC. However, S. mitis was unable to bind factor H. The S. pneumoniae TIGR4 strain pspC was expressed in the S. mitis SK142 strain to create a S. mitis pspC+ strain. Immunoblots demonstrated the S. mitis pspC+ strain expressed PspC, and flow cytometry confirmed this resulted in Factor H binding to S. mitis, reduced susceptibility to complement and improved survival in whole human blood compared to the wild-type S. mitis strain. However, in mouse models the S. mitis pspC+ strain remained unable to establish persistent infection. Unlike S. pneumoniae strains, culture in serum or blood did not support increased CFU of the S. mitis strains. These results suggest S. mitis is highly sensitive to opsonisation with complement partially due to an inability to bind Factor H, but even when complement sensitivity was reduced by expression of pspC, poor growth in physiological fluid limited the virulence of S. mitis in mice.
Highlights
The nasopharyngeal commensal Streptococcus pneumoniae is a frequent cause of pneumonia, septicaemia, and meningitis, and is one of the most common causes of death due to a microorganism globally (Fitzwater et al, 2012)
To assess whether differences in sensitivity to complement independent of capsule expression may underpin the relatively low virulence of S. mitis strains we investigated C3b/iC3b deposition on four S. pneumoniae capsular serotypes (4, 19C, 36, and 45) and four S. mitis strains, three of which express S. pneumoniae capsular serotypes (19C, 36, and 45)(Figure 1A)
Our finding that S. mitis strains are more susceptible to complement than S. pneumoniae strains could be one reason underpinning the relatively low virulence of S. mitis
Summary
The nasopharyngeal commensal Streptococcus pneumoniae is a frequent cause of pneumonia, septicaemia, and meningitis, and is one of the most common causes of death due to a microorganism globally (Fitzwater et al, 2012). Recent work has shown that many S. mitis strains express a capsule, some of which are structurally identical to S. pneumoniae capsular serotypes (Skov Sørensen et al, 2016). We have previously expressed the S. pneumoniae TIGR4 strain serotype (ST) 4 capsule, a virulent capsular serotype, in an S. mitis strain and shown that this improves immune evasion (Rukke et al, 2014). Unlike the S. pneumoniae TIGR4 strain, the S. mitis ST4 strain was still unable to cause sustained infection in mice. These data indicate that the differences in the virulence potential of S. pneumoniae and S. mitis are not related to just expression of a capsule but must reflect additional differences between the species
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