Reviving disused antibiotics against Gram-negative ESKAPE pathogens : combination with the polyaminoisoprenyl potentiator NV716
(2022)
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- Authors
- Supervisors
- Van Bambeke, Françoise
- Abstract
- Gram-negative ESKAPE pathogens are responsible for increases in multidrug-resistant infections worldwide. Poor permeability and active efflux cause intrinsic resistance to many antibiotics. Besides, these pathogens can also adopt specific lifestyles like intracellular survival and biofilm formation where bacteria can switch to dormant phenotypes poorly responsive to antibiotics. This thesis investigated the capacity of the polyaminoisoprenyl potentiator NV716 to revive disused antibiotics against Gram-negative bacteria using planktonic, intracellular and biofilm models. We showed that NV716 re-sensitizes Gram-negative bacteria to disused antibiotics by binding to the lipopolysaccharides (LPS) of the outer membrane, permeabilizing this membrane as well as downregulating quorum sensing regulated processes. Therefore, our work highlights a strong potential for this compound as an adjuvant therapy against difficult-to-treat Gram-negative organisms, and suggests that NV716 deserves further investigations, notably in in-vivo models of infections.
- Affiliations
Citations
Wang, G. (2022). Reviving disused antibiotics against Gram-negative ESKAPE pathogens : combination with the polyaminoisoprenyl potentiator NV716. https://hdl.handle.net/2078.5/108886