The role of host and microbial factors in the pathogenesis of pneumococcal bacteraemia arising from a single bacterial cell bottleneck..pdf (1.28 MB)
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The Role of Host and Microbial Factors in the Pathogenesis of Pneumococcal Bacteraemia Arising from a Single Bacterial Cell Bottleneck

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journal contribution
posted on 20.07.2015, 12:51 by A. Gerlini, L. Colomba, L. Furi, T. Braccini, A. S. Manso, A. Pammolli, Bo Wang, A. Vivi, M. Tassini, N. van Rooijen, G. Pozzi, S. Ricci, P. W. Andrew, U. Koedel, E. R. Moxon, M. R. Oggioni
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.

History

Citation

PLoS Pathogens, 2014, 10 (3), e1004026

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Biological Sciences/Department of Genetics

Version

VoR (Version of Record)

Published in

PLoS Pathogens

Publisher

Public Library of Science

issn

1553-7366

eissn

1553-7374

Acceptance date

10/02/2014

Copyright date

2014

Available date

20/07/2015

Publisher version

http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004026

Language

en