Dr Aurélie Crabbé - Host metabolites modulate bacterial susceptibility to antibiotics

Réalisation : 25 septembre 2020 Mise en ligne : 25 septembre 2020
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Antibiotic susceptibility of bacterialpathogens is typically evaluated using in vitro assays that do not consider thecomplex host microenvironment. This may help explaining a significantdiscrepancy between antibiotic efficacy in vitro and in vivo for chronic lunginfections, with some antibiotics being effective in vitro but not in vivo orvice versa. We previously demonstrated that lung epithelial cells enhance theactivity of aminoglycoside antibiotics against the opportunistic pathogen Pseudomonas aeruginosa, yet themechanism behind was unknown. I will present mechanistic insights on how lungepithelial cells stimulate aminoglycoside activity. To this end, an in vivo-like 3-D lung epithelial cellmodel was used. We report that conditioned medium of 3-D lung cells, containingsecreted but not cellular components, potentiated the bactericidal activity ofaminoglycosides against P. aeruginosa,including resistant clinical isolates, and several other pathogens. We foundthat 3-D lung cells secreted endogenous metabolites that modulateaminoglycoside activity, and provide evidence on the mode of action. Ourfindings reveal a cross-talk between host and bacterial metabolic pathways,that influence downstream activity of antibiotics. Understanding the underlyingbasis of the discrepancy between the activity of antibiotics in vitro and invivo may lead to improved diagnostic approaches and pave the way towards novelmeans to stimulate antibiotic activity.



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