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Article

Molecular Interactions of Carbapenem Antibiotics with the Multidrug Efflux Transporter AcrB of Escherichia coli

Department of Physics, University of Cagliari, 09042 Monserrato (CA), Italy
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Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(3), 860; https://doi.org/10.3390/ijms21030860
Received: 14 January 2020 / Accepted: 26 January 2020 / Published: 29 January 2020
(This article belongs to the Special Issue Computer Simulation on Membrane Receptors)
The drug/proton antiporter AcrB, engine of the major efflux pump AcrAB(Z)-TolC of Escherichia coli and other bacteria, is characterized by its impressive ability to transport chemically diverse compounds, conferring a multi-drug resistance (MDR) phenotype. Although hundreds of small molecules are known to be AcrB substrates, only a few co-crystal structures are available to date. Computational methods have been therefore intensively employed to provide structural and dynamical fingerprints related to transport and inhibition of AcrB. In this work, we performed a systematic computational investigation to study the interaction between representative carbapenem antibiotics and AcrB. We focused on the interaction of carbapenems with the so-called distal pocket, a region known for its importance in binding inhibitors and substrates of AcrB. Our findings reveal how the different physico-chemical nature of these antibiotics is reflected on their binding preference for AcrB. The molecular-level information provided here could help design new antibiotics less susceptible to the efflux mechanism. View Full-Text
Keywords: antibiotic resistance; Gram-negative bacteria; resistance nodulation-cell division transporters; AcrB; molecular docking; molecular dynamics simulations; binding free energy calculations antibiotic resistance; Gram-negative bacteria; resistance nodulation-cell division transporters; AcrB; molecular docking; molecular dynamics simulations; binding free energy calculations
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MDPI and ACS Style

Atzori, A.; Malloci, G.; Cardamone, F.; Bosin, A.; Vargiu, A.V.; Ruggerone, P. Molecular Interactions of Carbapenem Antibiotics with the Multidrug Efflux Transporter AcrB of Escherichia coli. Int. J. Mol. Sci. 2020, 21, 860. https://doi.org/10.3390/ijms21030860

AMA Style

Atzori A, Malloci G, Cardamone F, Bosin A, Vargiu AV, Ruggerone P. Molecular Interactions of Carbapenem Antibiotics with the Multidrug Efflux Transporter AcrB of Escherichia coli. International Journal of Molecular Sciences. 2020; 21(3):860. https://doi.org/10.3390/ijms21030860

Chicago/Turabian Style

Atzori, Alessio, Giuliano Malloci, Francesca Cardamone, Andrea Bosin, Attilio V. Vargiu, and Paolo Ruggerone. 2020. "Molecular Interactions of Carbapenem Antibiotics with the Multidrug Efflux Transporter AcrB of Escherichia coli" International Journal of Molecular Sciences 21, no. 3: 860. https://doi.org/10.3390/ijms21030860

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