4.7 Article

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

期刊

ISCIENCE
卷 25, 期 12, 页码 -

出版社

CELL PRESS
DOI: 10.1016/j.isci.2022.105522

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资金

  1. German Federal Ministry of Education and Research within the initiative e:Med-network of systems-medicine [FKZ: 01ZX01707C]
  2. German Federal Ministry of Education and Research within the Measures for the Establishment of Systems Medicine, project SYSIMIT (BMBF eMed project SYSIMIT) [FKZ: 01ZX1308B]
  3. Helmholtz Association [ZT-0027]
  4. Helmholtz Association within the initiative Immunology and Inflammation, project Aging and Metabolic Programming'' (AMPro)
  5. Helmholtz Initiative on Personalized Medicine - iMed
  6. Bundesministerium fur Bildung, und Forschung (BMBF) [031L0237C]
  7. Volkswagenstiftung [96732]
  8. Khalifa University

向作者/读者索取更多资源

This study developed a mathematical model to investigate chronic Staphylococcus aureus infection. The model suggested a therapeutic strategy using heat-killed S. aureus, which was tested in vivo. The results showed that the treatment protocol eliminated the infection and restored immune system function.
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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