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Phage activation in Staphylococcus aureus during deep-seated human infections

Research Project
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01.08.2021
 - 01.08.2023

The Gram-positive bacterium Staphylococcus aureus causes a wide variety of infectious diseases that are associated with substantial morbidity and mortality. Clinical isolates of S. aureus display vast genetic diversity, which is mainly determined by the presence of mobile genetic elements, comprising phages, and genomic islands. Phages mediate most genetic exchange among S. aureus strains, including the dissemination of resistance genes and virulence factors. Previous research has suggested that phage activation in S. aureus occurs regularly in infected host tissues. On the other hand, phage therapy has regained interest as a non-conventional strategy for urgently needed novel approaches to control infection. Endogenous phage activation might interfere with such approaches. This proposal aims to quantify the extent of phage activation in Staphylococcus aureus during deep-seated human infections and to determine its impact on therapy. I will first quantify phage activation in freshly frozen surgical samples from patients with deep-seated S. aureus infections. I will focus on samples containing S. aureus strains that are representative of major lineages as determined by whole-genome sequencing. I will then establish patient-mimicking in-vitro conditions to recapitulate in-vivo phage activation for identifying underlying molecular mechanisms and potential heterogeneity at the single-cell level. Finally, I will determine the impact of in vivo -like phage activation on S. aureus susceptibility to antimicrobials and phage therapy. Overall, this project will determine the relevance and impact of an understudied, but likely critical aspect of the major human pathogen S. aureus during human infections.

Funding

Phage activation in Staphylococcus aureus during deep-seated human infections

Weitere ausländische Förderagenturen (GrantsTool), 08.2021-08.2023 (25)
PI : Bumann, Dirk.
CI : Antelo Varela, Minia.

Members (2)

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Dirk Bumann

Principal Investigator
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Minia Antelo Varela

Co-Investigator