iScience (Dec 2022)

In silico predicted therapy against chronic Staphylococcus aureus infection leads to bacterial clearance in vivo

  • Lito A. Papaxenopoulou,
  • Gang Zhao,
  • Sahamoddin Khailaie,
  • Konstantinos Katsoulis-Dimitriou,
  • Ingo Schmitz,
  • Eva Medina,
  • Haralampos Hatzikirou,
  • Michael Meyer-Hermann

Journal volume & issue
Vol. 25, no. 12
p. 105522

Abstract

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Summary: Staphylococcus aureus can lead to chronic infections and abscesses in internal organs including kidneys, which are associated with the expansion of myeloid-derived suppressor cells (MDSCs) and their suppressive effect on T cells. Here, we developed a mathematical model of chronic S. aureus infection that incorporates the T-cell suppression by MDSCs and suggests therapeutic strategies for S. aureus clearance. A therapeutic protocol with heat-killed S. aureus (HKSA) was quantified in silico and tested in vivo. Contrary to the conventional administration of heat-killed bacteria as vaccination prior to infection, we administered HKSA as treatment in chronically infected hosts. Our treatment eliminated S. aureus in kidneys of all chronically S. aureus-infected mice, reduced MDSCs, and reversed T-cell dysfunction by inducing acute inflammation during ongoing, chronic infection. This study is a guideline for a treatment protocol against chronic S. aureus infection and renal abscesses by repurposing heat-killed treatments, directed by mathematical modeling.

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