Clonal population expansion of Staphylococcus aureus occurs due to escape from a finite number of intraphagocyte niches

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.

Biodelivery of therapeutic extracellular vesicles: should mononuclear phagocytes always be feared?

“…These approaches involve either manipulation of nanomaterials by surface coating with protective factors or changing their shape, or inhibiting and depleting MPS cells ( Liu et al, 2017 ; Ai et al, 2018 ; Xia et al, 2019 ; Mills et al, 2022 ; Lu et al, 2023 ), and should be combined to increase the biological efficacy. It might be a good idea to use bacteria as an example, as they develop different mechanisms to escape phagocytosis, allowing them to expand and weaken the host’s immune system ( Leseigneur et al, 2020 ; Pidwill et al, 2023 ).…”

A Multilayered Imaging and Microfluidics Approach for Evaluating the Effect of Fibrinolysis in Staphylococcus aureus Biofilm Formation

“…S. aureus Newman strain tagged with green fluorescent protein (GFP) was gently sourced by Prof. S. Foster [ 41 ] (Florey Institute for Host Pathogen Interactions; University of Sheffield, School of Biosciences). S. aureus was grown in Tryptic Soy Broth (TSB, Tryptone Soya Broth, CASO Broth, Soybean Casein digest Broth, Casein Soya Broth; STBMTSB12 Millipore, Darmstadt, Germany) under the resistance of kanamycin (10 µg/mL; Sigma-Aldrich, Darmstadt, Germany) at 37 °C and 200 rpm and collected on the day of the experiment at an optical density (O.D.)…”