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Title: The Role of Host and Microbial Factors in the Pathogenesis of Pneumococcal Bacteraemia Arising from a Single Bacterial Cell Bottleneck
Authors: Gerlini, A.
Colomba, L.
Furi, L.
Braccini, T.
Manso, A. S.
Pammolli, A.
Wang, Bo
Vivi, A.
Tassini, M.
van Rooijen, N.
Pozzi, G.
Ricci, S.
Andrew, P. W.
Koedel, U.
Moxon, E. R.
Oggioni, M. R.
First Published: 20-Mar-2014
Publisher: Public Library of Science
Citation: PLoS Pathogens, 2014, 10 (3), e1004026
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.
DOI Link: 10.1371/journal.ppat.1004026
ISSN: 1553-7366
eISSN: 1553-7374
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2014 Gerlini et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Mathematics

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