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Clonal population expansion of Staphylococcus aureus occurs due to escape from a finite number of intraphagocyte niches
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Clonal population expansion of Staphylococcus aureus occurs due to escape from a finite number of intraphagocyte niches
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Journal Article
Clonal population expansion of Staphylococcus aureus occurs due to escape from a finite number of intraphagocyte niches
2023
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
