Biophysical Society Thematic Meeting | Stockholm 2022

Physical and Quantitative Approaches to Overcome Antibiotic Resistance

Poster Abstracts

2-POS Board 2 INVESTIGATION OF THE BINDING PROPENSITIES OF ANTIBIOTICS ON THE SURFACE OF MEX TRANSPORTERS Mohd Athar 1 ; Attilio Vittorio Vargiu 1 ; Giuliano Malloci 1 ; Paolo Ruggerone 1 ; 1 University of Cagliari, Physics Department, Cagliari, Italy The World Health Organization (WHO) has identified antimicrobial resistance as one of the main global public health concerns. Efflux pumps of the RND (Resistance Nodulation-cell Division) superfamily such as MexB, MexD, MexF, and MexY of Pseudomonas aeruginosa play an essential role in multidrug resistance (both intrinsic and acquired) in Gram-negative bacteria Structural studies performed on MexB and homologous transporters in other Gram-negative bacteria revealed the presence of two main substrate recognition sites, accessed by substrate molecules through up to four (to date) different entry channels. Efforts at understanding correlations between the physico-chemical properties of compounds and their behaviour as substrates, non-substrates, or inhibitors of RND transporters have mostly relied on data about the interaction of compounds with the two main recognition sites, namely the access pocket and the deep binding pocket. However, considering also their interaction with protein channels and possibly other undetected sites could provide precious hints regarding both specificity and susceptibility. Under these premises, we performed a systematic blind ensemble-docking study addressing the binding propensities of several classes of antibiotics to the whole surface of the Mex transporters of P. aeruginosa. Our findings were employed to rationalize experimental data about the specificities of the compounds towards the different Mex transporters.

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