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Faculté de Médecine
Faculté de Médecine
MASTER THESIS
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Thesis, COLLÉGIALITÉ

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Putters, Florence ULiège
Promotor(s) : Oury, Cécile ULiège
Date of defense : 2-Jul-2024 • Permalink : http://hdl.handle.net/2268.2/20545
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Title : Thesis, COLLÉGIALITÉ
Author : Putters, Florence ULiège
Date of defense  : 2-Jul-2024
Advisor(s) : Oury, Cécile ULiège
Committee's member(s) : Pirotte, Bernard ULiège
Piel, Géraldine ULiège
Hayette, Marie-Pierre ULiège
Language : English
Number of pages : 47
Keywords : [en] Drug repurposing
[en] Staphylococcus aureus
[en] Antibiotics
[en] Cross-resistance
Discipline(s) : Life sciences > Microbiology
Human health sciences > Cardiovascular & respiratory systems
Institution(s) : Université de Liège, Liège, Belgique
Degree: Master en sciences biomédicales, à finalité approfondie
Faculty: Master thesis of the Faculté de Médecine

Abstract

[en] Antimicrobial resistance accounts for an annual mortality of 1.27 million deaths and this number is estimated to increase to 10 million deaths per year by 2050. One pathogen of particular concern is methicillin-resistant Staphylococcus aureus which can induce life threatening diseases such as infective endocarditis, pneumonia, or osteomyelitis. The high mortality rate related to infection with Staphylococcus aureus strains that are resistant to last-resort antibiotics including vancomycin and daptomycin, urges for novel treatment options.
Recently, the antiplatelet drug ticagrelor was found to possess bactericidal properties against Gram-positive and resistant Gram-positive bacteria including methicillin-resistant Staphylococcus aureus. The antibacterial properties of ticagrelor were corroborated by several clinical studies, describing a reduced infection risk in patients treated with ticagrelor compared to other P2Y12 antagonists.
This thesis aims to characterize cross-resistance of ticagrelor with conventional anti-methicillin-resistant Staphylococcus aureus antibiotics vancomycin and daptomycin, as well as the combinatory antibacterial effect of ticagrelor with these last-resort antibiotics against antibiotic-resistant Staphylococcus aureus strains.
We show no cross-resistance between ticagrelor and the last-resort antibiotic vancomycin. In contrast, the daptomycin-resistant SADR-2 strain containing mutations in genes encoding for ClpPG94D and RpoBA477D was resistant to ticagrelor, while in vitro-generated ticagrelor-resistant strains remained sensitive to daptomycin. Notably, ticagrelor showed additive antibacterial effects when combined with last-resort antibiotics vancomycin and daptomycin against methicillin-resistant and vancomycin-intermediate Staphylococcus aureus.
Our results highlight the potential of combining ticagrelor with conventionally used antibiotics in a clinical setting against difficult to treat Staphylococcus aureus infections. Furthermore, ticagrelor might prove beneficial compared to other P2Y12 inhibitors in the prevention of Staphylococcus aureus infections in patients that are at increased risk of developing infections and who need antiplatelet treatment.


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Author

  • Putters, Florence ULiège Université de Liège > Master sc. bioméd., fin. approf.

Promotor(s)

Committee's member(s)

  • Pirotte, Bernard ULiège Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
    ORBi View his publications on ORBi
  • Piel, Géraldine ULiège Université de Liège - ULiège > Département de pharmacie > Développement de nanomédicaments
    ORBi View his publications on ORBi
  • Hayette, Marie-Pierre ULiège Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Bact., mycologie, parasitologie, virologie, microbio.
    ORBi View his publications on ORBi
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  • Total number of downloads 6










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