Structure of the catalytic domain of the colistin resistance enzyme MCR-1

Stojanoski, Vlatko; Sankaran, Banumathi; Prasad, B. V.  Venkataram; Poirel, Laurent; Nordmann, Patrice; Palzkill, Timothy

doi:10.1186/s12915-016-0303-0

Title: Structure of the catalytic domain of the colistin resistance enzyme MCR-1

Abstract

Due to the paucity of novel antibiotics, colistin has become a last resort antibiotic for treating multidrug resistant bacteria. Colistin acts by binding the lipid A component of lipopolysaccharides and subsequently disrupting the bacterial membrane. The recently identified plasmid-encoded MCR-1 enzyme is the first transmissible colistin resistance determinant and is a cause for concern for the spread of this resistance trait. MCR-1 is a phosphoethanolamine transferase that catalyzes the addition of phosphoethanolamine to lipid A to decrease colistin affinity. The structure of the catalytic domain of MCR-1 at 1.32 Å reveals the active site is similar to that of related phosphoethanolamine transferases. The putative nucleophile for catalysis, threonine 285, is phosphorylated in cMCR-1 and a zinc is present at a conserved site in addition to three zincs more peripherally located in the active site. As noted for catalytic domains of other phosphoethanolamine transferases, binding sites for the lipid A and phosphatidylethanolamine substrates are not apparent in the cMCR-1 structure, suggesting that they are present in the membrane domain.

Authors:

Stojanoski, Vlatko ^[1]; Sankaran, Banumathi ^[2]; Prasad, B. V. Venkataram ^[3]; Poirel, Laurent ^[4]; Nordmann, Patrice ^[5];

^[1]

Baylor College of Medicine, Houston, TX (United States). Verna and Marrs McLean Dept. of Biochemistry and Molecular Biology; Baylor College of Medicine, Houston, TX (United States). Dept. of Pharmacology
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Berkeley Center for Structural Biology, Molecular Biophysics and Integrated Bioimaging
Baylor College of Medicine, Houston, TX (United States). Verna and Marrs McLean Dept. of Biochemistry and Molecular Biology
Univ. of Fribourg (Switzerland). Lab. of Signal and Image Processing (INSERM), Infection, Antimicrobials, Modelling, Evolution (IAME), Dept. of Medicine, Medical and Molecular Microbiology Emerging Antibiotic Resistance Unit
Univ. of Fribourg (Switzerland). Lab. of Signal and Image Processing (INSERM), Infection, Antimicrobials, Modelling, Evolution (IAME), Dept. of Medicine, Medical and Molecular Microbiology Emerging Antibiotic Resistance Unit; Univ. of Lausanne (Switzerland). Univ. Hospital Center

Publication Date:: 2016-09-21

Research Org.:: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Sponsoring Org.:: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH); Robert Welch Foundation

OSTI Identifier:: 1377497

Grant/Contract Number:: AC02-05CH11231; T32 AI55449

Resource Type:: Accepted Manuscript

Journal Name:: BMC Biology

Additional Journal Information:: Journal Volume: 14; Journal Issue: 1; Journal ID: ISSN 1741-7007

Publisher:: BioMed Central

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES

Citation Formats


                    Stojanoski, Vlatko, Sankaran, Banumathi, Prasad, B. V.  Venkataram, Poirel, Laurent, Nordmann, Patrice, and Palzkill, Timothy. Structure of the catalytic domain of the colistin resistance enzyme MCR-1.  United States: N. p., 2016. 
Web.  doi:10.1186/s12915-016-0303-0.

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                    Stojanoski, Vlatko, Sankaran, Banumathi, Prasad, B. V.  Venkataram, Poirel, Laurent, Nordmann, Patrice, & Palzkill, Timothy. Structure of the catalytic domain of the colistin resistance enzyme MCR-1.  United States.  https://doi.org/10.1186/s12915-016-0303-0

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                    Stojanoski, Vlatko, Sankaran, Banumathi, Prasad, B. V.  Venkataram, Poirel, Laurent, Nordmann, Patrice, and Palzkill, Timothy. Wed .  
"Structure of the catalytic domain of the colistin resistance enzyme MCR-1".  United States.  https://doi.org/10.1186/s12915-016-0303-0.  https://www.osti.gov/servlets/purl/1377497.

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@article{osti_1377497,

  title        = {Structure of the catalytic domain of the colistin resistance enzyme MCR-1},

  author       = {Stojanoski, Vlatko and Sankaran, Banumathi and Prasad, B. V.  Venkataram and Poirel, Laurent and Nordmann, Patrice and Palzkill, Timothy},

  abstractNote = {Due to the paucity of novel antibiotics, colistin has become a last resort antibiotic for treating multidrug resistant bacteria. Colistin acts by binding the lipid A component of lipopolysaccharides and subsequently disrupting the bacterial membrane. The recently identified plasmid-encoded MCR-1 enzyme is the first transmissible colistin resistance determinant and is a cause for concern for the spread of this resistance trait. MCR-1 is a phosphoethanolamine transferase that catalyzes the addition of phosphoethanolamine to lipid A to decrease colistin affinity. The structure of the catalytic domain of MCR-1 at 1.32 Å reveals the active site is similar to that of related phosphoethanolamine transferases. The putative nucleophile for catalysis, threonine 285, is phosphorylated in cMCR-1 and a zinc is present at a conserved site in addition to three zincs more peripherally located in the active site. As noted for catalytic domains of other phosphoethanolamine transferases, binding sites for the lipid A and phosphatidylethanolamine substrates are not apparent in the cMCR-1 structure, suggesting that they are present in the membrane domain.},

  doi          = {10.1186/s12915-016-0303-0},

  journal      = {BMC Biology},

  number       = 1,

  volume       = 14,

  place        = {United States},

  year         = {2016},

  month        = {9}

}

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Works referenced in this record:

Recent developments in classical density modification
journal, March 2010

Cowtan, Kevin
Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
DOI: 10.1107/S090744490903947X

Overview of the CCP 4 suite and current developments
journal, March 2011

Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D.
Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
DOI: 10.1107/S0907444910045749

Fortifying the barrier: the impact of lipid A remodelling on bacterial pathogenesis
journal, June 2013

Needham, Brittany D.; Trent, M. Stephen
Nature Reviews Microbiology, Vol. 11, Issue 7
DOI: 10.1038/nrmicro3047

Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases
journal, September 2013

Munoz-Price, L. Silvia; Poirel, Laurent; Bonomo, Robert A.
The Lancet Infectious Diseases, Vol. 13, Issue 9
DOI: 10.1016/S1473-3099(13)70190-7

Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes
journal, May 1986

Studier, F. William; Moffatt, Barbara A.
Journal of Molecular Biology, Vol. 189, Issue 1, p. 113-130
DOI: 10.1016/0022-2836(86)90385-2

Structures of aminoarabinose transferase ArnT suggest a molecular basis for lipid A glycosylation
journal, February 2016

Petrou, V. I.; Herrera, C. M.; Schultz, K. M.
Science, Vol. 351, Issue 6273
DOI: 10.1126/science.aad1172

ThreaDom: extracting protein domain boundary information from multiple threading alignments
journal, June 2013

Xue, Zhidong; Xu, Dong; Wang, Yan
Bioinformatics, Vol. 29, Issue 13
DOI: 10.1093/bioinformatics/btt209

Plasmid-Mediated Colistin-Resistant Escherichia coli in Bacteremia in Switzerland
journal, March 2016

Nordmann, Patrice; Lienhard, Reto; Kieffer, Nicolas
Clinical Infectious Diseases, Vol. 62, Issue 10
DOI: 10.1093/cid/ciw124

I-TASSER: a unified platform for automated protein structure and function prediction
journal, March 2010

Roy, Ambrish; Kucukural, Alper; Zhang, Yang
Nature Protocols, Vol. 5, Issue 4
DOI: 10.1038/nprot.2010.5

REFMAC 5 dictionary: organization of prior chemical knowledge and guidelines for its use
journal, November 2004

Vagin, Alexei A.; Steiner, Roberto A.; Lebedev, Andrey A.
Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12
DOI: 10.1107/S0907444904023510

Towards automated crystallographic structure refinement with phenix.refine
journal, March 2012

Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Echols, Nathaniel
Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4
DOI: 10.1107/S0907444912001308

Enzymatic Mechanisms of Phosphate and Sulfate Transfer
journal, August 2006

Cleland, W. Wallace; Hengge, Alvan C.
Chemical Reviews, Vol. 106, Issue 8
DOI: 10.1021/cr050287o

Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions
journal, November 2004

Krissinel, E.; Henrick, K.
Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12
DOI: 10.1107/S0907444904026460

Methods used in the structure determination of bovine mitochondrial F1 ATPase
journal, January 1996

Abrahams, J. P.; Leslie, A. G. W.
Acta Crystallographica Section D Biological Crystallography, Vol. 52, Issue 1
DOI: 10.1107/S0907444995008754

Scaling and assessment of data quality
journal, December 2005

Evans, Philip
Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 1, p. 72-82
DOI: 10.1107/S0907444905036693

The I-TASSER Suite: protein structure and function prediction
journal, December 2014

Yang, Jianyi; Yan, Renxiang; Roy, Ambrish
Nature Methods, Vol. 12, Issue 1
DOI: 10.1038/nmeth.3213

Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study
journal, February 2016

Liu, Yi-Yun; Wang, Yang; Walsh, Timothy R.
The Lancet Infectious Diseases, Vol. 16, Issue 2
DOI: 10.1016/S1473-3099(15)00424-7

I-TASSER server for protein 3D structure prediction
journal, January 2008

Zhang, Yang
BMC Bioinformatics, Vol. 9, Issue 1
DOI: 10.1186/1471-2105-9-40

UCSF Chimera?A visualization system for exploratory research and analysis
journal, January 2004

Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C.
Journal of Computational Chemistry, Vol. 25, Issue 13
DOI: 10.1002/jcc.20084

Multivariate phase combination improves automated crystallographic model building
journal, June 2010

Skubák, Pavol; Waterreus, Willem-Jan; Pannu, Navraj S.
Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 7
DOI: 10.1107/S0907444910014642

The mechanism of the alkaline phosphatase reaction: insights from NMR, crystallography and site-specific mutagenesis
journal, November 1999

Holtz, Kathleen M.; Kantrowitz, Evan R.
FEBS Letters, Vol. 462, Issue 1-2
DOI: 10.1016/S0014-5793(99)01448-9

Co-occurrence of extended spectrum β lactamase and MCR-1 encoding genes on plasmids
journal, March 2016

Haenni, Marisa; Poirel, Laurent; Kieffer, Nicolas
The Lancet Infectious Diseases, Vol. 16, Issue 3
DOI: 10.1016/S1473-3099(16)00007-4

Plasmid-mediated colistin resistance: an additional antibiotic resistance menace
journal, May 2016

Nordmann, P.; Poirel, L.
Clinical Microbiology and Infection, Vol. 22, Issue 5
DOI: 10.1016/j.cmi.2016.03.009

iMOSFLM : a new graphical interface for diffraction-image processing with MOSFLM
journal, March 2011

Battye, T. Geoff G.; Kontogiannis, Luke; Johnson, Owen
Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
DOI: 10.1107/S0907444910048675

The Buccaneer software for automated model building. 1. Tracing protein chains
journal, August 2006

Cowtan, Kevin
Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 9
DOI: 10.1107/S0907444906022116

A short history of SHELX
journal, December 2007

Sheldrick, George M.
Acta Crystallographica Section A Foundations of Crystallography, Vol. 64, Issue 1, p. 112-122
DOI: 10.1107/S0108767307043930

An Inner Membrane Enzyme in Salmonella and Escherichia coli That Transfers 4-Amino-4-deoxy-l-arabinose to Lipid A : INDUCTION IN POLYMYXIN-RESISTANT MUTANTS AND ROLE OF A NOVEL LIPID-LINKED DONOR
journal, September 2001

Trent, M. Stephen; Ribeiro, Anthony A.; Lin, Shanhua
Journal of Biological Chemistry, Vol. 276, Issue 46
DOI: 10.1074/jbc.M106961200

The Structure of the Neisserial Lipooligosaccharide Phosphoethanolamine Transferase A (LptA) Required for Resistance to Polymyxin
journal, September 2013

Wanty, Christopher; Anandan, Anandhi; Piek, Susannah
Journal of Molecular Biology, Vol. 425, Issue 18
DOI: 10.1016/j.jmb.2013.06.029

MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009

Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J.
Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1
DOI: 10.1107/S0907444909042073

Automatic protein structure solution from weak X-ray data
journal, November 2013

Skubák, Pavol; Pannu, Navraj S.
Nature Communications, Vol. 4, Issue 1
DOI: 10.1038/ncomms3777

The PmrA-Regulated pmrC Gene Mediates Phosphoethanolamine Modification of Lipid A and Polymyxin Resistance in Salmonella enterica
journal, June 2004

Lee, H.; Hsu, F. -F.; Turk, J.
Journal of Bacteriology, Vol. 186, Issue 13
DOI: 10.1128/JB.186.13.4124-4133.2004

REFMAC 5 for the refinement of macromolecular crystal structures
journal, March 2011

Murshudov, Garib N.; Skubák, Pavol; Lebedev, Andrey A.
Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
DOI: 10.1107/S0907444911001314

Predicting transmembrane protein topology with a hidden markov model: application to complete genomes11Edited by F. Cohen
journal, January 2001

Krogh, Anders; Larsson, Björn; von Heijne, Gunnar
Journal of Molecular Biology, Vol. 305, Issue 3
DOI: 10.1006/jmbi.2000.4315

PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
DOI: 10.1107/S0907444909052925

Emergence of the mcr-1 colistin resistance gene in carbapenem-resistant Enterobacteriaceae
journal, March 2016

Du, Hong; Chen, Liang; Tang, Yi-Wei
The Lancet Infectious Diseases, Vol. 16, Issue 3
DOI: 10.1016/S1473-3099(16)00056-6

Colistin: The Revival of Polymyxins for the Management of Multidrug-Resistant Gram-Negative Bacterial Infections
journal, May 2005

Falagas, M. E.; Kasiakou, S. K.; Saravolatz, L. D.
Clinical Infectious Diseases, Vol. 40, Issue 9
DOI: 10.1086/429323

Crystallographic study of the phosphoethanolamine transferase EptC required for polymyxin resistance and motility in Campylobacter jejuni
journal, September 2014

Fage, Christopher D.; Brown, Dusty B.; Boll, Joseph M.
Acta Crystallographica Section D Biological Crystallography, Vol. 70, Issue 10
DOI: 10.1107/S1399004714017623

Experimental phasing with SHELXC / D / E : combining chain tracing with density modification
journal, March 2010

Sheldrick, George M.
Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
DOI: 10.1107/S0907444909038360

Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria
journal, November 2014

Olaitan, Abiola O.; Morand, Serge; Rolain, Jean-Marc
Frontiers in Microbiology, Vol. 5
DOI: 10.3389/fmicb.2014.00643

Resistance to polymyxins: Mechanisms, frequency and treatment options
journal, August 2010

Falagas, Matthew E.; Rafailidis, Petros I.; Matthaiou, Dimitrios K.
Drug Resistance Updates, Vol. 13, Issue 4-5
DOI: 10.1016/j.drup.2010.05.002

The PDB_REDO server for macromolecular structure model optimization
journal, May 2014

Joosten, Robbie P.; Long, Fei; Murshudov, Garib N.
IUCrJ, Vol. 1, Issue 4
DOI: 10.1107/S2052252514009324

Plasmid-mediated carbapenem and colistin resistance in a clinical isolate of Escherichia coli
journal, March 2016

Poirel, Laurent; Kieffer, Nicolas; Liassine, Nadia
The Lancet Infectious Diseases, Vol. 16, Issue 3
DOI: 10.1016/S1473-3099(16)00006-2

Enzymatic Mechanisms of Phosphate and Sulfate Transfer
journal, October 2006

Cleland, W. Wallace; Hengge, Alvan C.
ChemInform, Vol. 37, Issue 44
DOI: 10.1002/chin.200644271

Characterization of a Bacillus megaterium strain with metal bioremediation potential and in silico discovery of novel cadmium binding motifs in the regulator, CadC
journal, March 2021

Kumari, Weerasingha Mudiyanselage Nilmini H.; Thiruchittampalam, Shalini; Weerasinghe, Mahinagoda Siril Samantha
Applied Microbiology and Biotechnology, Vol. 105, Issue 6
DOI: 10.1007/s00253-021-11193-2

Exploring the gas access routes in a [NiFeSe] hydrogenase using crystals pressurized with krypton and oxygen
journal, August 2020

Zacarias, Sónia; Temporão, Adriana; Carpentier, Philippe
JBIC Journal of Biological Inorganic Chemistry, Vol. 25, Issue 6
DOI: 10.1007/s00775-020-01814-y

Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation
journal, February 2021

Tillu, Vikas A.; Rae, James; Gao, Ya
Nature Communications, Vol. 12, Issue 1
DOI: 10.1038/s41467-021-21035-4

Overview of the CCP4 suite and current developments.
text, January 2011

Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D.
Apollo - University of Cambridge Repository
DOI: 10.17863/cam.52322

PHENIX: a comprehensive Python-based system for macromolecular structure solution.
text, January 2010

Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
Apollo - University of Cambridge Repository
DOI: 10.17863/cam.45787

Works referencing / citing this record:

Definition of a Family of Nonmobile Colistin Resistance (NMCR‐1) Determinants Suggests Aquatic Reservoirs for MCR‐4
journal, April 2019

Zhang, Huimin; Wei, Wenhui; Huang, Man
Advanced Science
DOI: 10.1002/advs.201900038

Mcr colistin resistance gene: a systematic review of current diagnostics and detection methods
journal, July 2018

Osei Sekyere, John
MicrobiologyOpen, Vol. 8, Issue 4
DOI: 10.1002/mbo3.682

Structural and functional insights into MCR-2 mediated colistin resistance
journal, September 2018

Wang, Xudong; Lu, Qiong; Qi, Jianxun
Science China Life Sciences, Vol. 61, Issue 11
DOI: 10.1007/s11427-018-9363-4

Development of novel antibodies for detection of mobile colistin-resistant bacteria contaminated in meats
journal, November 2018

He, Xiaohua; Mavrici, Daniela; Patfield, Stephanie
Scientific Reports, Vol. 8, Issue 1
DOI: 10.1038/s41598-018-34764-2

Synthesis of DNA-guided silver nanoparticles on a graphene oxide surface: enhancing the antibacterial effect and the wound healing activity
journal, January 2018

Tong, Chunyi; Zou, Wei; Ning, Weimin
RSC Advances, Vol. 8, Issue 49
DOI: 10.1039/c8ra04933e

Synthesis of silver nanoparticle-decorated hydroxyapatite (HA@Ag) poriferous nanocomposites and the study of their antibacterial activities
journal, January 2018

Ni, Zhihui; Gu, Xiuxian; He, Yali
RSC Advances, Vol. 8, Issue 73
DOI: 10.1039/c8ra08148d

Structure of a lipid A phosphoethanolamine transferase suggests how conformational changes govern substrate binding
journal, February 2017

Anandan, Anandhi; Evans, Genevieve L.; Condic-Jurkic, Karmen
Proceedings of the National Academy of Sciences, Vol. 114, Issue 9
DOI: 10.1073/pnas.1612927114

Mechanistic insights into transferable polymyxin resistance among gut bacteria
journal, February 2018

Xu, Yongchang; Lin, Jingxia; Cui, Tao
Journal of Biological Chemistry, Vol. 293, Issue 12
DOI: 10.1074/jbc.ra117.000924

Can octapeptin antibiotics combat extensively drug-resistant (XDR) bacteria?
journal, June 2018

Blaskovich, Mark A. T.; Pitt, Miranda E.; Elliott, Alysha G.
Expert Review of Anti-infective Therapy, Vol. 16, Issue 6
DOI: 10.1080/14787210.2018.1483240

Structure and function of lipid A–modifying enzymes
journal, September 2019

Anandan, Anandhi; Vrielink, Alice
Annals of the New York Academy of Sciences, Vol. 1459, Issue 1
DOI: 10.1111/nyas.14244

MCR-1.6, a New MCR Variant Carried by an IncP Plasmid in a Colistin-Resistant Salmonella enterica Serovar Typhimurium Isolate from a Healthy Individual
journal, March 2017

Lu, Xin; Hu, Yongfei; Luo, Ming
Antimicrobial Agents and Chemotherapy, Vol. 61, Issue 5
DOI: 10.1128/aac.02632-16

Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes
journal, March 2017

Poirel, Laurent; Jayol, Aurélie; Nordmann, Patrice
Clinical Microbiology Reviews, Vol. 30, Issue 2
DOI: 10.1128/cmr.00064-16

Characterization of Two Novel Lipopolysaccharide Phosphoethanolamine Transferases in Pasteurella multocida and Their Role in Resistance to Cathelicidin-2
journal, September 2017

Harper, Marina; Wright, Amy; St. Michael, Frank
Infection and Immunity, Vol. 85, Issue 11
DOI: 10.1128/iai.00557-17

Detection of Colistin-Resistant MCR-1-Positive Escherichia coli by Use of Assays Based on Inhibition by EDTA and Zeta Potential
journal, October 2017

Esposito, Fernanda; Fernandes, Miriam R.; Lopes, Ralf
Journal of Clinical Microbiology, Vol. 55, Issue 12
DOI: 10.1128/jcm.00835-17

Development and Multicentric Validation of a Lateral Flow Immunoassay for Rapid Detection of MCR-1-Producing Enterobacteriaceae
journal, March 2019

Volland, Hervé; Dortet, Laurent; Bernabeu, Sandrine
Journal of Clinical Microbiology, Vol. 57, Issue 5
DOI: 10.1128/jcm.01454-18

An Evolutionarily Conserved Mechanism for Intrinsic and Transferable Polymyxin Resistance
journal, April 2018

Xu, Yongchang; Wei, Wenhui; Lei, Sheng
mBio, Vol. 9, Issue 2
DOI: 10.1128/mbio.02317-17

Development of New Tools to Detect Colistin-Resistance among Enterobacteriaceae Strains
journal, December 2018

Bardet, Lucie; Rolain, Jean-Marc
Canadian Journal of Infectious Diseases and Medical Microbiology, Vol. 2018
DOI: 10.1155/2018/3095249

Expanding landscapes of the diversified mcr-1-bearing plasmid reservoirs
journal, July 2017

Wang, Qingjing; Sun, Jian; Li, Jun
Microbiome, Vol. 5, Issue 1
DOI: 10.1186/s40168-017-0288-0

Defining ICR-Mo, an intrinsic colistin resistance determinant from Moraxella osloensis
journal, May 2018

Wei, Wenhui; Srinivas, Swaminath; Lin, Jingxia
PLOS Genetics, Vol. 14, Issue 5
DOI: 10.1371/journal.pgen.1007389

Molecular characteristics of mcr-1-carrying plasmids and new mcr-1 variant recovered from polyclonal clinical Escherichia coli from Argentina and Canada
journal, July 2017

Tijet, Nathalie; Faccone, Diego; Rapoport, Melina
PLOS ONE, Vol. 12, Issue 7
DOI: 10.1371/journal.pone.0180347

Crystal Structure of the Catalytic Domain of MCR-1 (cMCR-1) in Complex with d-Xylose
journal, April 2018

Liu, Zhao-Xin; Han, Zhenggang; Yu, Xiao-Li
Crystals, Vol. 8, Issue 4
DOI: 10.3390/cryst8040172

Design, Synthesis and Biological Evaluation of 1-Phenyl-2-(phenylamino) Ethanone Derivatives as Novel MCR-1 Inhibitors
journal, July 2019

Lan, Xiu-juan; Yan, Hai-tao; Lin, Feng
Molecules, Vol. 24, Issue 15
DOI: 10.3390/molecules24152719

Comprehensive proteomic and metabolomic profiling of mcr-1-mediated colistin resistance in Escherichia coli
journal, June 2019

Li, Hui; Wang, Yingyu; Meng, Qingshi
International Journal of Antimicrobial Agents, Vol. 53, Issue 6
DOI: 10.1016/j.ijantimicag.2019.02.014

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Structures of aminoarabinose transferase ArnT suggest a molecular basis for lipid A glycosylation

Journal Article Petrou, Vasileios I. ; Herrera, Carmen M. ; Schultz, Kathryn M. ; ... - Science

Polymyxins are antibiotics used in the last line of defense to combat multidrug-resistant infections by Gram-negative bacteria. Polymyxin resistance arises through charge modification of the bacterial outer membrane with the attachment of the cationic sugar 4-amino-4-deoxy-L-arabinose to lipid A, a reaction catalyzed by the integral membrane lipid-to-lipid glycosyltransferase 4-amino-4-deoxy-L-arabinose transferase (ArnT). In this article, we report crystal structures of ArnT from Cupriavidus metallidurans, alone and in complex with the lipid carrier undecaprenyl phosphate, at 2.8 and 3.2 angstrom resolution, respectively. The structures show cavities for both lipidic substrates, which converge at the active site. A structural rearrangement occurs on undecaprenylmore »« less
Cited by 48
https://doi.org/10.1126/science.aad1172

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Structure of the essential inner membrane lipopolysaccharide–PbgA complex

Journal Article Clairfeuille, Thomas ; Buchholz, Kerry R. ; Li, Qingling ; ... - Nature (London)

Lipopolysaccharide (LPS) resides in the outer membrane of Gram-negative bacteria where it is responsible for barrier function. LPS can cause death as a result of septic shock, and its lipid A core is the target of polymyxin antibiotics. Despite the clinical importance of polymyxins and the emergence of multidrug resistant strains, our understanding of the bacterial factors that regulate LPS biogenesis is incomplete. Here we characterize the inner membrane protein PbgA and report that its depletion attenuates the virulence of Escherichia coli by reducing levels of LPS and outer membrane integrity. In contrast to previous claims that PbgA functions asmore »« less
Cited by 1
https://doi.org/10.1038/s41586-020-2597-x

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Structural insights into lipoprotein N-acylation by Escherichia coli apolipoprotein N-acyltransferase

Journal Article Noland, Cameron L. ; Kattke, Michele D. ; Diao, Jingyu ; ... - Proceedings of the National Academy of Sciences of the United States of America

Gram-negative bacteria express a diverse array of lipoproteins that are essential for various aspects of cell growth and virulence, including nutrient uptake, signal transduction, adhesion, conjugation, sporulation, and outer membrane protein folding. Lipoprotein maturation requires the sequential activity of three enzymes that are embedded in the cytoplasmic membrane. First, phosphatidylglycerol:prolipoprotein diacylglyceryl transferase (Lgt) recognizes a conserved lipobox motif within the prolipoprotein signal sequence and catalyzes the addition of diacylglycerol to an invariant cysteine. The signal sequence is then cleaved by signal peptidase II (LspA) to give an N-terminal S-diacylglyceryl cysteine. Finally, apolipoprotein N-acyltransferase (Lnt) catalyzes the transfer of the sn-1-acylmore »« less
Cited by 20
https://doi.org/10.1073/pnas.1707813114

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