Pidwill, G.R., Pyrah, J.F., Sutton, J.A.F. orcid.org/0000-0002-0440-610X et al. (3 more authors) (2023) Clonal population expansion of Staphylococcus aureus occurs due to escape from a finite number of intraphagocyte niches. Scientific Reports, 13 (1). 1188. pp. 1-11.
Abstract
Staphylococcus aureus is a human commensal and also an opportunist pathogen causing life threatening infections. During S. aureus disease, the abscesses that characterise infection can be clonal, whereby a large bacterial population is founded by a single or few organisms. Our previous work has shown that macrophages are responsible for restricting bacterial growth such that a population bottleneck occurs and clonality can emerge. A subset of phagocytes fail to control S. aureus resulting in bacterial division, escape and founding of microabscesses that can seed other host niches. Here we investigate the basis for clonal microabscess formation, using in vitro and in silico models of S. aureus macrophage infection. Macrophages that fail to control S. aureus are characterised by formation of intracellular bacterial masses, followed by cell lysis. High-resolution microscopy reveals that most macrophages had internalised only a single S. aureus, providing a conceptual framework for clonal microabscess generation, which was supported by a stochastic individual-based, mathematical model. Once a threshold of masses was reached, increasing the number of infecting bacteria did not result in greater mass numbers, despite enhanced phagocytosis. This suggests a finite number of permissive, phagocyte niches determined by macrophage associated factors. Increased understanding of the parameters of infection dynamics provides avenues for development of rational control measures.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Bacteriology; Cellular microbiology; Microbiology; Pathogens |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 25 Jan 2023 11:21 |
Last Modified: | 25 Jan 2023 11:21 |
Published Version: | http://dx.doi.org/10.1038/s41598-023-27928-2 |
Status: | Published |
Publisher: | Springer Science and Business Media LLC |
Refereed: | Yes |
Identification Number: | 10.1038/s41598-023-27928-2 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:195592 |