Dataset Information

The role of host and microbial factors in the pathogenesis of pneumococcal bacteraemia arising from a single bacterial cell bottleneck.

ABSTRACT: The pathogenesis of bacteraemia after challenge with one million pneumococci of three isogenic variants was investigated. Sequential analyses of blood samples indicated that most episodes of bacteraemia were monoclonal events providing compelling evidence for a single bacterial cell bottleneck at the origin of invasive disease. With respect to host determinants, results identified novel properties of splenic macrophages and a role for neutrophils in early clearance of pneumococci. Concerning microbial factors, whole genome sequencing provided genetic evidence for the clonal origin of the bacteraemia and identified SNPs in distinct sub-units of F0/F1 ATPase in the majority of the ex vivo isolates. When compared to parental organisms of the inoculum, ex-vivo pneumococci with mutant alleles of the F0/F1 ATPase had acquired the capacity to grow at low pH at the cost of the capacity to grow at high pH. Although founded by a single cell, the genotypes of pneumococci in septicaemic mice indicate strong selective pressure for fitness, emphasising the within-host complexity of the pathogenesis of invasive disease.

SUBMITTER: Gerlini A

PROVIDER: S-EPMC3961388 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The role of host and microbial factors in the pathogenesis of pneumococcal bacteraemia arising from a single bacterial cell bottleneck.

Gerlini Alice A Colomba Leonarda L Furi Leonardo L Braccini Tiziana T Manso Ana Sousa AS Pammolli Andrea A Wang Bo B Vivi Antonio A Tassini Maria M van Rooijen Nico N Pozzi Gianni G Ricci Susanna S Ricci Susanna S Andrew Peter W PW Koedel Uwe U Moxon E Richard ER Oggioni Marco R MR

PLoS pathogens 20140320 3

The pathogenesis of bacteraemia after challenge with one million pneumococci of three isogenic variants was investigated. Sequential analyses of blood samples indicated that most episodes of bacteraemia were monoclonal events providing compelling evidence for a single bacterial cell bottleneck at the origin of invasive disease. With respect to host determinants, results identified novel properties of splenic macrophages and a role for neutrophils in early clearance of pneumococci. Concerning mic ...[more]

PMID: 24651834

Similar Datasets

Project description:BackgroundStreptococcus pneumoniae (the pneumococcus) is the world's foremost microbial pathogen, killing more people each year than HIV, TB or malaria. The capacity to penetrate deeper host tissues contributes substantially to the ability of this organism to cause disease. Here we investigated, for the first time, functional genomics modulation of 3 pneumococcal strains (serotype 2 [D39], serotype 4 [WCH43] and serotype 6A [WCH16]) during transition from the nasopharynx to lungs to blood and to brain of mice at both promoter and domain activation levels.ResultsWe found 7 highly activated transcription factors (TFs) [argR, codY, hup, rpoD, rr02, scrR and smrC] capable of binding to a large number of up-regulated genes, potentially constituting the regulatory backbone of pneumococcal pathogenesis. Strain D39 showed a distinct profile in employing a large number of TFs during blood infection. Interestingly, the same highly activated TFs used by D39 in blood are also used by WCH16 and WCH43 during brain infection. This indicates that different pneumococcal strains might activate a similar set of TFs and regulatory elements depending on the final site of infection. Hierarchical clustering analysis showed that all the highly activated TFs, except rpoD, clustered together with a high level of similarity in all 3 strains, which might suggest redundancy in the regulatory roles of these TFs during infection. Discriminant function analysis of the TFs in various niches highlights differential regulatory backgrounds of the 3 strains, and pathogenesis data confirms codY as the most significant predictor discriminating between these strains in various niches, particularly in the blood. Moreover, the predicted TF and domain activation profiles of the 3 strains correspond with their distinct pathogenicity characteristics.ConclusionsOur findings suggest that the pneumococcus changes the short binding sites in the promoter regions of genes in a niche-specific manner to enhance its ability to disseminate from one host niche to another. This study provides a framework for an improved understanding of the dynamics of pneumococcal pathogenesis, and opens a new avenue into similar investigations in other pathogenic bacteria.

Dataset Information

The role of host and microbial factors in the pathogenesis of pneumococcal bacteraemia arising from a single bacterial cell bottleneck.

Publications

The role of host and microbial factors in the pathogenesis of pneumococcal bacteraemia arising from a single bacterial cell bottleneck.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets