Ressource pédagogique : Dr Aurélie Crabbé - Host metabolites modulate bacterial susceptibility to antibiotics

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Antibiotic susceptibility of bacterial pathogens is typically evaluated using in vitro assays that do not consider the complex host microenvironment. This may help explaining a significant discrepancy between antibiotic efficacy in vitro and in vivo for chronic lung infections, with some antibiotics being effective in vitro but not in vivo or vice versa. We previously demonstrated that lung epithelial cells enhance the activity of aminoglycoside antibiotics against the opportunistic pathogen Pseudomonas aeruginosa, yet the mechanism behind was unknown. I will present mechanistic insights on how lung epithelial cells stimulate aminoglycoside activity. To this end, an in vivo-like 3-D lung epithelial cell model was used. We report that conditioned medium of 3-D lung cells, containing secreted but not cellular components, potentiated the bactericidal activity of aminoglycosides against P. aeruginosa, including resistant clinical isolates, and several other pathogens. We found that 3-D lung cells secreted endogenous metabolites that modulate aminoglycoside activity, and provide evidence on the mode of action. Our findings reveal a cross-talk between host and bacterial metabolic pathways, that influence downstream activity of antibiotics. Understanding the underlying basis of the discrepancy between the activity of antibiotics in vitro and in vivo may lead to improved diagnostic approaches and pave the way towards novel means to stimulate antibiotic activity.  

"Domaine(s)" et indice(s) Dewey

• Maladies des poumons (hypertension artérielle pulmonaire, hypertension pulmonaire, maladie obstructive respiratoire chronique, maladies respiratoires, ouvrages généraux sur les maladies des bronches et des poumons) (616.24)

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