PT  - JOURNAL ARTICLE
AU  - Jean-Philippe Corre
AU  - Dorian Obino
AU  - Pierre Nivoit
AU  - Aline Yatim
AU  - Taliah Schmitt
AU  - Guillaume Duménil
TI  - Anti-thrombotic treatment enhances antibiotic efficiency in a humanized model of meningococcemia
AID  - 10.1101/2022.01.10.475613
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.01.10.475613
4099  - http://biorxiv.org/content/early/2022/01/10/2022.01.10.475613.short
4100  - http://biorxiv.org/content/early/2022/01/10/2022.01.10.475613.full
AB  - Meningococcal infections remain particularly difficult to treat. Despite antibiotic therapy, the state of the patients often rapidly deteriorates. Early clinical studies suggest that meningococci acquire a form of resistance to antibiotic treatments during infections. Taking advantage of a humanized animal model of infection, we confirm that adherent bacteria become highly resistant to antibiotic treatments as early as 3-6 hours post infection, although fully sensitive in vitro. Within this time frame, meningococci adhere to the endothelium via their type IV pili, proliferate and eventually fill the vessel lumen. Using intravital imaging, we show that rapidly upon infection blood flow is dramatically decreased, thus limiting antibiotic access to infected vessels. Concomitantly, fibrin is deposited inside infected vessels in proximity to bacterial aggregates. Pharmacologically impairing thrombin generation by inhibiting Factor X activity not only improves blood flow in infected vessels, but also enhances the efficacy of the antibiotic treatment. Our results indicate that the combined administration of anticoagulants together with antibiotics might represent a therapeutic approach to treat meningococcal sepsis more efficiently.Competing Interest StatementThe authors have declared no competing interest.