Fig. 3: Schematic representation of the prospective assay designed to address existing gaps. | Communications Biology

Fig. 3: Schematic representation of the prospective assay designed to address existing gaps.

From: Advances in methods and concepts provide new insight into antibiotic fluxes across the bacterial membrane

Fig. 3

Red circles indicate sampling ___location (biopsy or collection) that are subjected to environmental conditions (green circle). Black text denotes the different proposed analyses to determine bacterial and molecules parameters. Different colors represent the respective methods and tools used during parameters analyses. Blue text indicates the recovery and analyses of parameters related to bacteria and molecules, with AI being used to highlight key points and specific insights. The analyses of the collected data pave the way for developing adapted animal models that consider the various identified parameters (e.g. local concentrations, combinations…). ATB: Antibiotic, MAMR: Membrane-associated mechanisms of resistance. “!A- !E” correspond to the response to the ”?A-?E” gaps mentioned in Fig. 1: - “!A”: In vivo drug concentration at infection site; - “!B”: Periplasmic active drug concentration determined in the absence or presence of an enzyme inhibitor, membrane permeabilizer, with/without target mutation, or using multiple combinations; - “!C”: Cytoplasmic active drug concentration determined in the absence or presence of an enzyme inhibitor or membrane permeabilizer, with/without target mutation, or using multiple combinations; -“!D”: Drug translocation through porin determined in the presence or absence of a membrane permeabilizer and relationship with the type of porin determined in the presence of identified porin; -“!E”: Drug translocation through efflux pump determined in the absence or presence of an efflux inhibitor/blocker and relationship with the type of efflux pump determined in the presence of identified pumps (e.g. AcrAB, AcrEF, ..etc). ‘T’ represents the formatting of information that can be used by clinicians during the selection of antibiotics or drug combination, or by pharmacochemists for the rational synthesis of new molecules. Finally, new strategies to counter MAMR are to be implemented to enhance clinical effectiveness. Created in BioRender. Vergalli, J. (2024) BioRender.com/h37t256.

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