Host-to-Host Transmission of Streptococcus pneumoniae Is Driven by Its Inflammatory Toxin, Pneumolysin

Abstract

SUMMARY Host-to-host transmission is a critical step for infection. Here we studied transmission of the opportunistic pathogen Streptococcus pneumoniae in an infant mouse model. Transmission from nasally colonized pups required high levels of bacterial shedding in nasal secretions and was temporally correlated with, and dependent upon, the acute inflammatory response. Pneumolysin, a pore-forming cytotoxin and major virulence determinant, was both necessary and sufficient to promote inflammation, which increased shedding and allowed for intralitter transmission. Direct contact between pups was not required for transmission indicating the importance of an environmental reservoir. An additional in vivo effect of pneumolysin was to enhance bacterial survival outside of the host. Our findings provide experimental evidence of a microbial strategy for transit to new hosts and explain why an organism expresses a toxin that damages the host upon which it depends.

Streptococcus pneumoniae: transmission, colonization and invasion

“…It is unclear whether immunity to other S. pneumoniae surface targets can block transmission. In this regard, immunization with Ply shows no effect on shedding and transmission, even though the toxin is required for spread between pups 16 . This result is not unexpected as Ply is not actively secreted, is not present on the cell surface and might be released only when pneumococci are lysed within the phagosome and therefore are not exposed to antibody 29 .…”

“…In the infant mouse model, dampening inflammation by intranasal treatment or the use of Tlr2 −/− index mice reduces shedding and transmission 16 . The single pneumococcal toxin, pneumolysin (Ply), has strong pro-inflammatory effects, and Ply-induced inflammation hastens clearance of bacteria from the URT 17 .…”

“…The single pneumococcal toxin, pneumolysin (Ply), has strong pro-inflammatory effects, and Ply-induced inflammation hastens clearance of bacteria from the URT 17 . Both a ply -knockout mutant and a point mutant, in which the toxin is unable to oligomerize to form pores after membrane insertion, reduced URT inflammation, shedding and the ability to transmit to littermates 16 . Additionally, intranasal administration of the purified toxin, but not the inactive toxoid (PdB), could complement the inflammation, shedding and transmission defect of the ply mutant.…”

“…Transmission through secretions of carriers could involve direct person-to-person contact or spread involving bacteria on contaminated surfaces. As evidence of the latter, in the mouse model, the co-housed dam is not colonized but has large numbers of S. pneumoniae on her teats, and in-cage switch experiments can serve as a source of contagion 9,16 . S. pneumoniae can also be easily cultured from common objects, such as soft toys recently handled by colonized children 20 .…”

“…Under ambient, nutrient-sufficient conditions, such as in ex vivo human saliva, pneumococci can survive for days 21 . Under nutrient-poor conditions, such as in airway surface fluid, bacterial expression of Ply increases ex vivo survival 16 . This effect can be explained by toxin dependent inflammation and, consequently, increased nutrients levels in secretions.…”