New Insight into Daptomycin Bioavailability and Localization in Staphylococcus aureus Biofilms by Dynamic Fluorescence Imaging.
Staphylococcus aureus is one of the most frequent pathogens responsible for biofilm-associated infections (BAI), and the choice of antibiotics to treat these infections remains a challenge for the medical community. In particular, daptomycin has been reported to fail against implant-associated S. aureus infections in clinical practice, while its association with rifampin remains a good candidate for BAI treatment. To improve our understanding of such resistance/tolerance toward daptomycin, we took advantage of the dynamic fluorescence imaging tools (time-lapse imaging and fluorescence recovery after photobleaching [FRAP]) to locally and accurately assess the antibiotic diffusion reaction in methicillin-susceptible and methicillin-resistant S. aureus biofilms. To provide a realistic representation of daptomycin action, we optimized an in vitro model built on the basis of our recently published in vivo mouse model of prosthetic vascular graft infections. We demonstrated that at therapeutic concentrations, daptomycin was inefficient in eradicating biofilms, while the matrix was not a shield to antibiotic diffusion and to its interaction with its bacterial target. In the presence of rifampin, daptomycin was still present in the vicinity of the bacterial cells, allowing prevention of the emergence of rifampin-resistant mutants. Conclusions derived from this study strongly suggest that S. aureus biofilm resistance/tolerance toward daptomycin may be more likely to be related to a physiological change involving structural modifications of the membrane, which is a strain-dependent process.
Institut des Sciences Moléculaires d'Orsay (ISMO), CNRS, Université Paris-Sud, Université Paris-Saclay, Orsay, France rym.boudjemaa@u-psud.fr.
Rym
R
Boudjemaa
Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.
Romain
R
Briandet
CHU Rennes, Rennes, France Université de Nantes, Faculté de Médecine, UPRES EA 3826, Nantes, France.
Matthieu
M
Revest
Université de Nantes, Faculté de Médecine, UPRES EA 3826, Nantes, France.
Cédric
C
Jacqueline
Université de Nantes, Faculté de Médecine, UPRES EA 3826, Nantes, France.
Jocelyne
J
Caillon
Institut des Sciences Moléculaires d'Orsay (ISMO), CNRS, Université Paris-Sud, Université Paris-Saclay, Orsay, France.
Marie-Pierre
MP
Fontaine-Aupart
Institut des Sciences Moléculaires d'Orsay (ISMO), CNRS, Université Paris-Sud, Université Paris-Saclay, Orsay, France.
Karine
K
Steenkeste
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D017576:Daptomycin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D036681:Fluorescence Recovery After Photobleaching; D008826:Microbial Sensitivity Tests; D012293:Rifampin / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D017576:Daptomycin; D012293:Rifampin