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

• Published in: iScience Vol. 25; no. 12; p. 105522
• Main Authors: Papaxenopoulou, Lito A., Zhao, Gang, Khailaie, Sahamoddin, Katsoulis-Dimitriou, Konstantinos, Schmitz, Ingo, Medina, Eva, Hatzikirou, Haralampos, Meyer-Hermann, Michael
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 22.12.2022; Elsevier
• Subjects: Immunity; Immunity
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.105522

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. [Display omitted] Model-driven quantified therapy protocol design against chronic Staphylococcus aureus infection•Treatment with heat-killed S. aureus eradicates S. aureus in vivo•Treatment induces acute inflammation during ongoing, chronic S. aureus infection•A proof-of-principle against renal S. aureus abscesses Immunity