Serotype-Dependent Effects on the Dynamics of Pneumococcal Colonization and Implications for Transmission

Abstract

Capsule is the major virulence factor and surface antigen of the opportunistic respiratory pathogen Streptococcus pneumoniae (Spn). Strains of Spn express at least 100 structurally and immunologically distinct types (serotypes) of capsule, but for unknown reasons only a few are common.

BlpC-mediated selfish program leads to rapid loss of Streptococcus pneumoniae clonal diversity during infection

“…No difference was observed in either the colonization density or clonal diversity of WT versus Δ cibAB Δ cbpD strains 1 day post-inoculation ( Figs 4A, B ). Thus, these fratricidal molecules that are important for in vivo competition during early hours following colonization (Abruzzo et al, 2022; Shen et al, 2019), do not lead to the observed decrease in diversity of Spn .…”

“…Given their higher carrying capacity of colonizing Spn , we postulated that infants may allow for larger N e values relative to adult mice (Kono et al, 2016; Siegel et al, 2015). We used a previously described carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution assay to determine what proportion of Spn are undergoing replication in vivo (Abruzzo et al, 2022; Siegel et al, 2014). We observed a pronounced reduction in the fluorescence intensity of CFSE among colonizing Spn at 19 hours post-inoculation, suggesting that a vast majority of cells have undergone division ( Figs 2D, S4 ).…”

“…Next, we evaluated the contribution of blp bacteriocins to inter- and intra-strain competition. When two Spn strains are co-inoculated into the same mouse in a murine colonization model, the 23F strain used in this work outcompeted another commonly used strain, TIGR4 (Abruzzo et al, 2022). The blp locus was not responsible for this inter-strain competitive advantage of the 23F strain, as both WT and Δ blp strains performed similarly in competition with TIGR4 ( Fig 4J ).…”

“…We tested whether these fratricidal molecules (CibAB and CbpD) were also responsible for altering the Spn population structure during colonization by constructing a diverse 4A, B). Thus, these fratricidal molecules that are important for in vivo competition during early hours following colonization (Abruzzo et al, 2022;Shen et al, 2019), do not lead to the observed decrease in diversity of Spn.…”

“…Spn mutants were constructed as previously described (Abruzzo et al, 2022;Aggarwal et al, 2021bAggarwal et al, , 2021a. Colonies were picked and inoculated in acidic Columbia broth (pH 6.6) and grown until an OD 595 of 0.05 followed by the addition of 5 µg/ml of 1:1 mix of CSP1 and CSP2 along with 500 ng of transforming DNA.…”