Dynamics of Intact MexAB-OprM Efflux Pump: Focusing on the MexA-OprM Interface

Lopez, Cesar A.; Travers, Timothy; Pos, Klaas M.; Zgurskaya, Helen I.; Gnanakaran, S.

doi:10.1038/s41598-017-16497-w

Title: Dynamics of Intact MexAB-OprM Efflux Pump: Focusing on the MexA-OprM Interface

Journal Article · Tue Nov 28 00:00:00 EST 2017 · Scientific Reports

DOI:https://doi.org/10.1038/s41598-017-16497-w· OSTI ID:1440470

Lopez, Cesar A. ^[1]; Travers, Timothy ^[1]; Pos, Klaas M. ^[2]; Zgurskaya, Helen I. ^[3]; Gnanakaran, S. ^[1]

Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Goethe Univ., Frankfurt (Germany). Inst. of Biochemistry. Cluster of Excellence Frankfurt
Univ. of Oklahoma, Norman, OK (United States). Dept. of Chemistry and Biochemistry

Antibiotic efflux is one of the most critical mechanisms leading to bacterial multidrug resistance. Antibiotics are effluxed out of the bacterial cell by a tripartite efflux pump, a complex machinery comprised of outer membrane, periplasmic adaptor, and inner membrane protein components. Understanding the mechanism of efflux pump assembly and its dynamics could facilitate discovery of novel approaches to counteract antibiotic resistance in bacteria. We built here an intact atomistic model of the Pseudomonas aeruginosa MexAB-OprM pump in a Gram-negative membrane model that contained both inner and outer membranes separated by a periplasmic space. All-atom molecular dynamics (MD) simulations confirm that the fully assembled pump is stable in the microsecond timescale. Using a combination of all-atom and coarse-grained MD simulations and sequence covariation analysis, we characterized the interface between MexA and OprM in the context of the entire efflux pump. These analyses suggest a plausible mechanism by which OprM is activated via opening of its periplasmic aperture through a concerted interaction with MexA.

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Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States); Univ. of Oklahoma, Norman, OK (United States); Goethe Univ., Frankfurt (Germany)

Sponsoring Organization:: USDOE; LANL Laboratory Directed Research and Development (LDRD) Program; Defense Threat Reduction Agency (DTRA) (United States); National Inst. of Health (NIH) (United States); German Research Foundation (DFG); Human Frontier Science Program (HFSP)

Grant/Contract Number:: AC52-06NA25396; HDTRA1-14-1-0019; AI052293; SFB807; EXC115; HFSP-RGP0034/2013

OSTI ID:: 1440470

Report Number(s):: LA-UR-16-27246

Journal Information:: Scientific Reports, Vol. 7; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 20 works

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References (104)

Nonphysical sampling distributions in Monte Carlo free-energy estimation: Umbrella sampling Torrie, G. M.; Valleau, J. P. Journal of Computational Physics, Vol. 23, Issue 2 https://doi.org/10.1016/0021-9991(77)90121-8	journal	February 1977
Assembly and Channel Opening in a Bacterial Drug Efflux Machine Bavro, Vassiliy N.; Pietras, Zbigniew; Furnham, Nicholas Molecular Cell, Vol. 30, Issue 1, p. 114-121 https://doi.org/10.1016/j.molcel.2008.02.015	journal	April 2008
Structure of the AcrAB–TolC multidrug efflux pump Du, Dijun; Wang, Zhao; James, Nathan R. Nature, Vol. 509, Issue 7501 https://doi.org/10.1038/nature13205	journal	April 2014
Tripartite assembly of RND multidrug efflux pumps Daury, Laetitia; Orange, François; Taveau, Jean-Christophe Nature Communications, Vol. 7, Issue 1 https://doi.org/10.1038/ncomms10731	journal	February 2016
Resistance Mechanisms in Pseudomonas aeruginosa and Other Nonfermentative Gram‐Negative Bacteria Hancock, Robert E. W. Clinical Infectious Diseases, Vol. 27, Issue s1 https://doi.org/10.1086/514909	journal	August 1998
Antibiotic efflux mechanisms Nikaido, Hiroshi; Zgurskaya, Helen I. Current Opinion in Infectious Diseases, Vol. 12, Issue 6 https://doi.org/10.1097/00001432-199912000-00001	journal	January 1999
The effects of active efflux pumps on antibiotic resistance in Pseudomonas aeruginosa Terzi, Huseyin Agah; Kulah, Canan; Ciftci, İhsan Hakkı World Journal of Microbiology and Biotechnology, Vol. 30, Issue 10 https://doi.org/10.1007/s11274-014-1692-2	journal	June 2014
Permeability of Pseudomonas aeruginosa outer membrane to hydrophilic solutes Yoshimura, F.; Nikaido, H. Journal of Bacteriology, Vol. 152, Issue 2 https://doi.org/10.1128/jb.152.2.636-642.1982	journal	November 1982
Comparison of simple potential functions for simulating liquid water Jorgensen, William L.; Chandrasekhar, Jayaraman; Madura, Jeffry D. The Journal of Chemical Physics, Vol. 79, Issue 2 https://doi.org/10.1063/1.445869	journal	July 1983
Decreased outer membrane permeability in imipenem-resistant mutants of Pseudomonas aeruginosa. Trias, J.; Dufresne, J.; Levesque, R. C. Antimicrobial Agents and Chemotherapy, Vol. 33, Issue 8 https://doi.org/10.1128/aac.33.8.1202	journal	August 1989
Breaking the Spell: Combating Multidrug Resistant ‘Superbugs’ Khan, Shahper N.; Khan, Asad U. Frontiers in Microbiology, Vol. 7 https://doi.org/10.3389/fmicb.2016.00174	journal	February 2016
Molecular dynamics flexible fitting: A practical guide to combine cryo-electron microscopy and X-ray crystallography Trabuco, Leonardo G.; Villa, Elizabeth; Schreiner, Eduard Methods, Vol. 49, Issue 2 https://doi.org/10.1016/j.ymeth.2009.04.005	journal	October 2009
Flexibility in a Drug Transport Accessory Protein: Molecular Dynamics Simulations of MexA Vaccaro, Loredana; Koronakis, Vassilis; Sansom, Mark S. P. Biophysical Journal, Vol. 91, Issue 2 https://doi.org/10.1529/biophysj.105.080010	journal	July 2006
Multidrug efflux transporter, AcrB—the pumping mechanism Murakami, S. Current Opinion in Structural Biology, Vol. 18, Issue 4 https://doi.org/10.1016/j.sbi.2008.06.007	journal	August 2008
Bacterial Multidrug Efflux Transporters Delmar, Jared A.; Su, Chih-Chia; Yu, Edward W. Annual Review of Biophysics, Vol. 43, Issue 1 https://doi.org/10.1146/annurev-biophys-051013-022855	journal	May 2014
Crystal structure of bacterial multidrug efflux transporter AcrB Murakami, Satoshi; Nakashima, Ryosuke; Yamashita, Eiki Nature, Vol. 419, Issue 6907 https://doi.org/10.1038/nature01050	journal	October 2002
Multiple conformational states and gate opening of outer membrane protein TolC revealed by molecular dynamics simulations: MD Simulation of TolC Wang, Beibei; Weng, Jingwei; Wang, Wenning Proteins: Structure, Function, and Bioinformatics, Vol. 82, Issue 9 https://doi.org/10.1002/prot.24573	journal	June 2014
Keep It Flexible: Driving Macromolecular Rotary Motions in Atomistic Simulations with GROMACS Kutzner, Carsten; Czub, Jacek; Grubmüller, Helmut Journal of Chemical Theory and Computation, Vol. 7, Issue 5 https://doi.org/10.1021/ct100666v	journal	March 2011
Isolation and characterization of antibiotic-resistant bacteria from pharmaceutical industrial wastewaters Tahrani, Leyla; Soufi, Leila; Mehri, Ines Microbial Pathogenesis, Vol. 89 https://doi.org/10.1016/j.micpath.2015.09.001	journal	December 2015
Lipid14: The Amber Lipid Force Field Dickson, Callum J.; Madej, Benjamin D.; Skjevik, Åge A. Journal of Chemical Theory and Computation, Vol. 10, Issue 2 https://doi.org/10.1021/ct4010307	journal	January 2014
Crystal Structure of the Periplasmic Component of a Tripartite Macrolide-Specific Efflux Pump Yum, Soohwan; Xu, Yongbin; Piao, Shunfu Journal of Molecular Biology, Vol. 387, Issue 5 https://doi.org/10.1016/j.jmb.2009.02.048	journal	April 2009
Structure of the periplasmic component of a bacterial drug efflux pump Higgins, M. K.; Bokma, E.; Koronakis, E. Proceedings of the National Academy of Sciences, Vol. 101, Issue 27 https://doi.org/10.1073/pnas.0400375101	journal	June 2004
Structure of the MacAB–TolC ABC-type tripartite multidrug efflux pump Fitzpatrick, Anthony W. P.; Llabrés, Salomé; Neuberger, Arthur Nature Microbiology, Vol. 2, Issue 7 https://doi.org/10.1038/nmicrobiol.2017.70	journal	May 2017
Keep it Flexible: Driving Macromolecular Rotary Motions in Atomistic Simulations with Gromacs Kutzner, Carsten; Czub, Jacek; Grubmueller, Helmut Biophysical Journal, Vol. 102, Issue 3 https://doi.org/10.1016/j.bpj.2011.11.927	journal	January 2012
Multidrug efflux pumps in Gram-negative bacteria and their role in antibiotic resistance Blair, Jessica MA; Richmond, Grace E.; Piddock, Laura JV Future Microbiology, Vol. 9, Issue 10 https://doi.org/10.2217/fmb.14.66	journal	October 2014
Interactions underlying assembly of the Escherichia coli AcrAB-TolC multidrug efflux system: Multidrug efflux system assembly Touzé, Thierry; Eswaran, Jeyanthy; Bokma, Evert Molecular Microbiology, Vol. 53, Issue 2 https://doi.org/10.1111/j.1365-2958.2004.04158.x	journal	June 2004
LAMBADA and InflateGRO2: Efficient Membrane Alignment and Insertion of Membrane Proteins for Molecular Dynamics Simulations Schmidt, Thomas H.; Kandt, Christian Journal of Chemical Information and Modeling, Vol. 52, Issue 10 https://doi.org/10.1021/ci3000453	journal	September 2012
Structural basis of RND-type multidrug exporters Yamaguchi, Akihito; Nakashima, Ryosuke; Sakurai, Keisuke Frontiers in Microbiology, Vol. 6 https://doi.org/10.3389/fmicb.2015.00327	journal	April 2015
Structural and Dynamical Insights into the Opening Mechanism of P. aeruginosa OprM Channel Phan, Gilles; Benabdelhak, Houssain; Lascombe, Marie-Bernard Structure, Vol. 18, Issue 4 https://doi.org/10.1016/j.str.2010.01.018	journal	March 2010
Computational Methodologies for Real-Space Structural Refinement of Large Macromolecular Complexes Goh, Boon Chong; Hadden, Jodi A.; Bernardi, Rafael C. Annual Review of Biophysics, Vol. 45, Issue 1 https://doi.org/10.1146/annurev-biophys-062215-011113	journal	July 2016
Mutations in MexB that affect the efflux of antibiotics with cytoplasmic targets Ohene-Agyei, Thelma; Lea, Jon D.; Venter, Henrietta FEMS Microbiology Letters, Vol. 333, Issue 1 https://doi.org/10.1111/j.1574-6968.2012.02594.x	journal	May 2012
An allosteric transport mechanism for the AcrAB-TolC multidrug efflux pump Wang, Zhao; Fan, Guizhen; Hryc, Corey F. eLife, Vol. 6 https://doi.org/10.7554/eLife.24905	journal	March 2017
The assembly and disassembly of the AcrAB-TolC three-component multidrug efflux pump Müller, Reinke Tobias; Pos, Klaas Martinus Biological Chemistry, Vol. 396, Issue 9-10 https://doi.org/10.1515/hsz-2015-0150	journal	September 2015
Functional Rotation Induced by Alternating Protonation States in the Multidrug Transporter AcrB: All-Atom Molecular Dynamics Simulations Yamane, Tsutomu; Murakami, Satoshi; Ikeguchi, Mitsunori Biochemistry, Vol. 52, Issue 43 https://doi.org/10.1021/bi400119v	journal	October 2013
Novel Strategies for the Treatment of Pseudomonas aeruginosa Infections Wagner, Stefanie; Sommer, Roman; Hinsberger, Stefan Journal of Medicinal Chemistry, Vol. 59, Issue 13 https://doi.org/10.1021/acs.jmedchem.5b01698	journal	February 2016
Crystal Structure of the Multidrug Exporter MexB from Pseudomonas aeruginosa Sennhauser, Gaby; Bukowska, Magdalena A.; Briand, Christophe Journal of Molecular Biology, Vol. 389, Issue 1 https://doi.org/10.1016/j.jmb.2009.04.001	journal	May 2009
Canonical sampling through velocity rescaling Bussi, Giovanni; Donadio, Davide; Parrinello, Michele The Journal of Chemical Physics, Vol. 126, Issue 1 https://doi.org/10.1063/1.2408420	journal	January 2007
Pseudoatomic Structure of the Tripartite Multidrug Efflux Pump AcrAB-TolC Reveals the Intermeshing Cogwheel-like Interaction between AcrA and TolC Jeong, Hyeongseop; Kim, Jin-Sik; Song, Saemee Structure, Vol. 24, Issue 2 https://doi.org/10.1016/j.str.2015.12.007	journal	February 2016
Within-host evolution of bacterial pathogens Didelot, Xavier; Walker, A. Sarah; Peto, Tim E. Nature Reviews Microbiology, Vol. 14, Issue 3 https://doi.org/10.1038/nrmicro.2015.13	journal	January 2016
Computational Study of Correlated Domain Motions in the AcrB Efflux Transporter Schulz, Robert; Vargiu, Attilio V.; Ruggerone, Paolo BioMed Research International, Vol. 2015 https://doi.org/10.1155/2015/487298	journal	January 2015
Particle mesh Ewald: An N ⋅log( N ) method for Ewald sums in large systems Darden, Tom; York, Darrin; Pedersen, Lee The Journal of Chemical Physics, Vol. 98, Issue 12 https://doi.org/10.1063/1.464397	journal	June 1993
Unilateral Access Regulation: Ground State Dynamics of the Pseudomonas aeruginosa Outer Membrane Efflux Duct OprM Koch, Dennis C.; Raunest, Martin; Harder, Tim Biochemistry, Vol. 52, Issue 1 https://doi.org/10.1021/bi3014714	journal	December 2012
Contribution of Outer Membrane Efflux Protein OprM to Antibiotic Resistance in Pseudomonas aeruginosa Independent of MexAB Zhao, Qixun; Li, Xian-Zhi; Srikumar, Ramakrishnan Antimicrobial Agents and Chemotherapy, Vol. 42, Issue 7 https://doi.org/10.1128/aac.42.7.1682	journal	July 1998
Drug export and allosteric coupling in a multidrug transporter revealed by molecular simulations Yao, Xin-Qiu; Kenzaki, Hiroo; Murakami, Satoshi Nature Communications, Vol. 1, Issue 1 https://doi.org/10.1038/ncomms1116	journal	November 2010
Molecular dynamics with coupling to an external bath Berendsen, H. J. C.; Postma, J. P. M.; van Gunsteren, W. F. The Journal of Chemical Physics, Vol. 81, Issue 8 https://doi.org/10.1063/1.448118	journal	October 1984
Mechanism of coupling drug transport reactions located in two different membranes Zgurskaya, Helen I.; Weeks, Jon W.; Ntreh, Abigail T. Frontiers in Microbiology, Vol. 6 https://doi.org/10.3389/fmicb.2015.00100	journal	February 2015
Understanding the mechanisms and drivers of antimicrobial resistance Holmes, Alison H.; Moore, Luke S. P.; Sundsfjord, Arnfinn The Lancet, Vol. 387, Issue 10014 https://doi.org/10.1016/s0140-6736(15)00473-0	journal	January 2016
Statistical Thermodynamics for Functionally Rotating Mechanism of the Multidrug Efflux Transporter AcrB Mishima, Hirokazu; Oshima, Hiraku; Yasuda, Satoshi The Journal of Physical Chemistry B, Vol. 119, Issue 8 https://doi.org/10.1021/jp5120724	journal	February 2015
Macroscopic conductivity of aqueous electrolyte solutions scales with ultrafast microscopic ion motions Balos, Vasileios; Imoto, Sho; Netz, Roland R. Freie Universität Berlin https://doi.org/10.17169/refubium-28486	text	January 2020
Polarizable Water Model for the Coarse-Grained MARTINI Force Field Yesylevskyy, Semen O.; Schäfer, Lars V.; Sengupta, Durba PLoS Computational Biology, Vol. 6, Issue 6 https://doi.org/10.1371/journal.pcbi.1000810	journal	June 2010
Opening the Channel: the Two Functional Interfaces of Pseudomonas aeruginosa OpmH with the Triclosan Efflux Pump TriABC Ntreh, Abigail T.; Weeks, Jon W.; Nickels, Logan M. Journal of Bacteriology, Vol. 198, Issue 23 https://doi.org/10.1128/jb.00535-16	journal	September 2016
Fitting Periplasmic Membrane Fusion Proteins to Inner Membrane Transporters: Mutations That Enable Escherichia coli AcrA To Function with Pseudomonas aeruginosa MexB Krishnamoorthy, G.; Tikhonova, E. B.; Zgurskaya, H. I. Journal of Bacteriology, Vol. 190, Issue 2 https://doi.org/10.1128/JB.01276-07	journal	November 2007
Escherichia coli Peptidoglycan Structure and Mechanics as Predicted by Atomic-Scale Simulations Gumbart, James C.; Beeby, Morgan; Jensen, Grant J. PLoS Computational Biology, Vol. 10, Issue 2 https://doi.org/10.1371/journal.pcbi.1003475	journal	February 2014
Structure and Function of TolC: The Bacterial Exit Duct for Proteins and Drugs Koronakis, Vassilis; Eswaran, Jeyanthy; Hughes, Colin Annual Review of Biochemistry, Vol. 73, Issue 1 https://doi.org/10.1146/annurev.biochem.73.011303.074104	journal	June 2004
Molecular Dynamics Computer Simulations of Multidrug rnd Efflux Pumps Ruggerone, Paolo; Vargiu, Attilio V.; Collu, Francesca Computational and Structural Biotechnology Journal, Vol. 5, Issue 6 https://doi.org/10.5936/csbj.201302008	journal	February 2013
g_wham—A Free Weighted Histogram Analysis Implementation Including Robust Error and Autocorrelation Estimates Hub, Jochen S.; de Groot, Bert L.; van der Spoel, David Journal of Chemical Theory and Computation, Vol. 6, Issue 12 https://doi.org/10.1021/ct100494z	journal	November 2010
Advances in the molecular dynamics flexible fitting method for cryo-EM modeling McGreevy, Ryan; Teo, Ivan; Singharoy, Abhishek Methods, Vol. 100 https://doi.org/10.1016/j.ymeth.2016.01.009	journal	May 2016
Drug Uptake Pathways of Multidrug Transporter AcrB Studied by Molecular Simulations and Site-Directed Mutagenesis Experiments Yao, Xin-Qiu; Kimura, Nobuhiro; Murakami, Satoshi Journal of the American Chemical Society, Vol. 135, Issue 20 https://doi.org/10.1021/ja310548h	journal	May 2013
Crystal Structure and Pair Potentials: A Molecular-Dynamics Study Parrinello, M.; Rahman, A. Physical Review Letters, Vol. 45, Issue 14 https://doi.org/10.1103/physrevlett.45.1196	journal	October 1980
Generating stereochemically acceptable protein pathways Farrell, Daniel W.; Speranskiy, Kirill; Thorpe, M. F. Proteins: Structure, Function, and Bioinformatics, Vol. 78, Issue 14 https://doi.org/10.1002/prot.22810	journal	September 2010
Conformational Flexibility in the Multidrug Efflux System Protein AcrA Mikolosko, Jonathan; Bobyk, Kostyantyn; Zgurskaya, Helen I. Structure, Vol. 14, Issue 3 https://doi.org/10.1016/j.str.2005.11.015	journal	March 2006
Crystal structure of the CusBA heavy-metal efflux complex of Escherichia coli Su, Chih-Chia; Long, Feng; Zimmermann, Michael T. Nature, Vol. 470, Issue 7335 https://doi.org/10.1038/nature09743	journal	February 2011
Molecular dynamics-based refinement and validation for sub-5 Å cryo-electron microscopy maps Singharoy, Abhishek; Teo, Ivan; McGreevy, Ryan eLife, Vol. 5 https://doi.org/10.7554/eLife.16105	journal	July 2016
Assembly and Channel Opening of Outer Membrane Protein in Tripartite Drug Efflux Pumps of Gram-negative Bacteria Xu, Yongbin; Moeller, Arne; Jun, So-Young Journal of Biological Chemistry, Vol. 287, Issue 15 https://doi.org/10.1074/jbc.m111.329375	journal	February 2012
UniProt: the universal protein knowledgebase Nucleic Acids Research, Vol. 45, Issue D1, p. D158-D169 https://doi.org/10.1093/nar/gkw1099	journal	November 2016
Pseudomonas aeruginosa – a phenomenon of bacterial resistance Yordanov, Daniel; Strateva, Tanya Journal of Medical Microbiology, Vol. 58, Issue 9 https://doi.org/10.1099/jmm.0.009142-0	journal	September 2009
Mechanistic Parallels in Bacterial and Human Multidrug Efflux Transporters Zgurskaya, H. I.; Nikaido, H. Current Protein & Peptide Science, Vol. 3, Issue 5 https://doi.org/10.2174/1389203023380512	journal	October 2002
An overview of bacterial efflux pumps and computational approaches to study efflux pump inhibitors Jamshidi, Shirin; Sutton, J. Mark; Rahman, Khondaker M. Future Medicinal Chemistry, Vol. 8, Issue 2 https://doi.org/10.4155/fmc.15.173	journal	February 2016
Sequence co-evolution gives 3D contacts and structures of protein complexes Hopf, Thomas A.; Schärfe, Charlotta P. I.; Rodrigues, João P. G. L. M. eLife, Vol. 3 https://doi.org/10.7554/eLife.03430	journal	September 2014
Improved side-chain torsion potentials for the Amber ff99SB protein force field Lindorff-Larsen, Kresten; Piana, Stefano; Palmo, Kim Proteins: Structure, Function, and Bioinformatics https://doi.org/10.1002/prot.22711	journal	January 2010
Crystal Structure of the Membrane Fusion Protein, MexA, of the Multidrug Transporter in Pseudomonas aeruginosa Akama, Hiroyuki; Matsuura, Takanori; Kashiwagi, Sachiko Journal of Biological Chemistry, Vol. 279, Issue 25 https://doi.org/10.1074/jbc.c400164200	journal	April 2004
Assembly of the MexAB-OprM Multidrug Pump of Pseudomonas aeruginosa: Component Interactions Defined by the Study of Pump Mutant Suppressors Nehme, D.; Poole, K. Journal of Bacteriology, Vol. 189, Issue 17 https://doi.org/10.1128/JB.00718-07	journal	June 2007
P-LINCS: A Parallel Linear Constraint Solver for Molecular Simulation Hess, Berk Journal of Chemical Theory and Computation, Vol. 4, Issue 1 https://doi.org/10.1021/ct700200b	journal	December 2007
The MARTINI Force Field: Coarse Grained Model for Biomolecular Simulations Marrink, Siewert J.; Risselada, H. Jelger; Yefimov, Serge The Journal of Physical Chemistry B, Vol. 111, Issue 27 https://doi.org/10.1021/jp071097f	journal	July 2007
Crystal Structure of the Drug Discharge Outer Membrane Protein, OprM, of Pseudomonas aeruginosa : DUAL MODES OF MEMBRANE ANCHORING AND OCCLUDED CAVITY END Akama, Hiroyuki; Kanemaki, Misa; Yoshimura, Masato Journal of Biological Chemistry, Vol. 279, Issue 51 https://doi.org/10.1074/jbc.C400445200	journal	October 2004
Cryo-Transmission Electron Microscopy of Frozen-Hydrated Sections of Escherichia coli and Pseudomonas aeruginosa Matias, V. R. F.; Al-Amoudi, A.; Dubochet, J. Journal of Bacteriology, Vol. 185, Issue 20 https://doi.org/10.1128/jb.185.20.6112-6118.2003	journal	October 2003
GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit Pronk, Sander; Páll, Szilárd; Schulz, Roland Bioinformatics, Vol. 29, Issue 7 https://doi.org/10.1093/bioinformatics/btt055	journal	February 2013
Multidrug-Resistant Gram-Negative Bacterial Infections in the Hospital Setting: Overview, Implications for Clinical Practice, and Emerging Treatment Options Cerceo, Elizabeth; Deitelzweig, Steven B.; Sherman, Bradley M. Microbial Drug Resistance, Vol. 22, Issue 5 https://doi.org/10.1089/mdr.2015.0220	journal	July 2016
A data-driven approach to modeling the tripartite structure of multidrug resistance efflux pumps: Modeling of Multidrug Resistance Efflux Pumps Phillips, Joshua L.; Gnanakaran, S. Proteins: Structure, Function, and Bioinformatics, Vol. 83, Issue 1 https://doi.org/10.1002/prot.24632	journal	November 2014
Structures of sequential open states in a symmetrical opening transition of the TolC exit duct Pei, Xue-Yuan; Hinchliffe, Philip; Symmons, Martyn F. Proceedings of the National Academy of Sciences, Vol. 108, Issue 5 https://doi.org/10.1073/pnas.1012588108	journal	January 2011
Robust and accurate prediction of residue–residue interactions across protein interfaces using evolutionary information Ovchinnikov, Sergey; Kamisetty, Hetunandan; Baker, David eLife, Vol. 3 https://doi.org/10.7554/elife.02030	journal	May 2014
Pseudomonas aeruginosa: all roads lead to resistance Breidenstein, Elena B. M.; de la Fuente-Núñez, César; Hancock, Robert E. W. Trends in Microbiology, Vol. 19, Issue 8 https://doi.org/10.1016/j.tim.2011.04.005	journal	August 2011
The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria Li, Xian-Zhi; Plésiat, Patrick; Nikaido, Hiroshi Clinical Microbiology Reviews, Vol. 28, Issue 2 https://doi.org/10.1128/cmr.00117-14	journal	March 2015
AcrA is a highly asymmetric protein capable of spanning the periplasm 1 1Edited by I. B. Holland Zgurskaya, Helen I.; Nikaido, Hiroshi Journal of Molecular Biology, Vol. 285, Issue 1 https://doi.org/10.1006/jmbi.1998.2313	journal	January 1999
RETRACTED ARTICLE: Profile of Virulence Factors in the Multi-Drug Resistant Pseudomonas aeruginosa Strains of Human Urinary Tract Infections (UTI) Habibi, Asghar; Honarmand, Ramin Iranian Red Crescent Medical Journal, Vol. 17, Issue 12 https://doi.org/10.5812/ircmj.26095	journal	December 2015
Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB Eicher, Thomas; Seeger, Markus A.; Anselmi, Claudio eLife, Vol. 3 https://doi.org/10.7554/eLife.03145	journal	September 2014
Outer membrane permeability and antibiotic resistance Delcour, Anne H. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1794, Issue 5 https://doi.org/10.1016/j.bbapap.2008.11.005	journal	May 2009
Molecular Dynamics and NMR Spectroscopy Studies of E. coli Lipopolysaccharide Structure and Dynamics Wu, Emilia L.; Engström, Olof; Jo, Sunhwan Biophysical Journal, Vol. 105, Issue 6 https://doi.org/10.1016/j.bpj.2013.08.002	journal	September 2013
Structure, mechanism and cooperation of bacterial multidrug transporters Du, Dijun; van Veen, Hendrik W.; Murakami, Satoshi Current Opinion in Structural Biology, Vol. 33 https://doi.org/10.1016/j.sbi.2015.07.015	journal	August 2015
Antibiotic resistance in Pseudomonas aeruginosa and alternative therapeutic options Chatterjee, Maitrayee; Anju, C. P.; Biswas, Lalitha International Journal of Medical Microbiology, Vol. 306, Issue 1 https://doi.org/10.1016/j.ijmm.2015.11.004	journal	January 2016
Structure of reconstituted bacterial membrane efflux pump by cryo-electron tomography Trépout, Sylvain; Taveau, Jean-Christophe; Benabdelhak, Houssain Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1798, Issue 10 https://doi.org/10.1016/j.bbamem.2010.06.019	journal	October 2010
Residue – Residue Potentials with a Favorable Contact Pair Term and an Unfavorable High Packing Density Term, for Simulation and Threading Miyazawa, Sanzo; Jernigan, Robert L. Journal of Molecular Biology, Vol. 256, Issue 3 https://doi.org/10.1006/jmbi.1996.0114	journal	March 1996
Sequential Mechanism of Assembly of Multidrug Efflux Pump AcrAB-TolC Tikhonova, Elena B.; Yamada, Yoichi; Zgurskaya, Helen I. Chemistry & Biology, Vol. 18, Issue 4 https://doi.org/10.1016/j.chembiol.2011.02.011	journal	April 2011
Catch me if you can: a biotinylated proteoliposome affinity assay for the investigation of assembly of the MexA-MexB-OprM efflux pump from Pseudomonas aeruginosa Ntsogo EnguÃ©nÃ©, VÃ©ronique Yvette; VerchÃ¨re, Alice; Phan, Gilles Frontiers in Microbiology, Vol. 6 https://doi.org/10.3389/fmicb.2015.00541	journal	June 2015
Interaction of antibacterial compounds with RND eﬄux pumps in Pseudomonas aeruginosa Dreier, Jürg; Ruggerone, Paolo Frontiers in Microbiology, Vol. 6 https://doi.org/10.3389/fmicb.2015.00660	journal	July 2015
Functional replacement of OprJ by OprM in the MexCD-OprJ multidrug efflux system of Pseudomonas aeruginosa Gotoh, Naomasa; Tsujimoto, Hideto; Nomura, Atsuko FEMS Microbiology Letters, Vol. 165, Issue 1 https://doi.org/10.1111/j.1574-6968.1998.tb13122.x	journal	August 1998
Multidrug Resistant and Extensively Drug Resistant Bacteria: A Study Basak, Silpi; Singh, Priyanka; Rajurkar, Monali Journal of Pathogens, Vol. 2016 https://doi.org/10.1155/2016/4065603	journal	January 2016
New OprM structure highlighting the nature of the N-terminal anchor Monlezun, Laura; Phan, Gilles; Benabdelhak, Houssain Frontiers in Microbiology, Vol. 6 https://doi.org/10.3389/fmicb.2015.00667	journal	July 2015
Electrophysiological Behavior of the TolC Channel-Tunnel in Planar Lipid Bilayers Andersen, C.; Hughes, C.; Koronakis, V. Journal of Membrane Biology, Vol. 185, Issue 1 https://doi.org/10.1007/s00232-001-0113-2	journal	January 2002
Permeability Barrier of Gram-Negative Cell Envelopes and Approaches To Bypass It Zgurskaya, Helen I.; López, Cesar A.; Gnanakaran, S. ACS Infectious Diseases, Vol. 1, Issue 11 https://doi.org/10.1021/acsinfecdis.5b00097	journal	August 2015
Ultra-fast FFT protein docking on graphics processors Ritchie, David W.; Venkatraman, Vishwesh Bioinformatics, Vol. 26, Issue 19 https://doi.org/10.1093/bioinformatics/btq444	journal	August 2010
The Importance of Efflux Systems in Antibiotic Resistance and Efflux Pump Inhibitors in the Management of Resistance [Antibiyotik Direncinde Dışa Atım Sistemlerinin ve Dirençle Mücadelede Dışa Atım Pompa İnhibitörlerinin Önemi] AygÜL, Abdurrahman Mikrobiyoloji Bulteni, Vol. 49, Issue 2 https://doi.org/10.5578/mb.8964	journal	April 2015
Contribution of the MexX-MexY-OprM Efflux System to Intrinsic Resistance in Pseudomonas aeruginosa Masuda, N.; Sakagawa, E.; Ohya, S. Antimicrobial Agents and Chemotherapy, Vol. 44, Issue 9 https://doi.org/10.1128/aac.44.9.2242-2246.2000	journal	September 2000
HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment Remmert, Michael; Biegert, Andreas; Hauser, Andreas Nature Methods, Vol. 9, Issue 2 https://doi.org/10.1038/nmeth.1818	journal	December 2011

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AcrB: a mean, keen, drug efflux machine Kobylka, Jessica; Kuth, Miriam S.; Müller, Reinke T. Annals of the New York Academy of Sciences, Vol. 1459, Issue 1 https://doi.org/10.1111/nyas.14239	journal	September 2019

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