Clinical Variants of New Delhi Metallo-β-Lactamase Are Evolving To Overcome Zinc Scarcity

Stewart, Alesha C.; Bethel, Christopher R.; VanPelt, Jamie; Bergstrom, Alex; Cheng, Zishuo; Miller, Callie G.; Williams, Cameron; Poth, Robert; Morris, Matthew; Lahey, Olivia; Nix, Jay C.; Tierney, David L.; Page, Richard C.; Crowder, Michael W.; Bonomo, Robert A.; Fast, Walter

doi:10.1021/acsinfecdis.7b00128

Title: Clinical Variants of New Delhi Metallo-β-Lactamase Are Evolving To Overcome Zinc Scarcity

Journal Article · Sat Sep 30 00:00:00 EDT 2017 · ACS Infectious Diseases

DOI:https://doi.org/10.1021/acsinfecdis.7b00128· OSTI ID:1426739

Stewart, Alesha C. ^[1]; Bethel, Christopher R. ^[2]; VanPelt, Jamie ^[3]; Bergstrom, Alex ^[3]; Cheng, Zishuo ^[3]; Miller, Callie G. ^[3]; Williams, Cameron ^[3]; Poth, Robert ^[3]; Morris, Matthew ^[3]; Lahey, Olivia ^[3]; Nix, Jay C. ^[4]; Tierney, David L. ^[3];

^[3];

^[5];

^[1]

Univ. of Texas, Austin, TX (United States). Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, and the LaMontagne Center for Infectious Disease
Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH (United States). Research Services
Miami University, Oxford, OH (United States). Department of Chemistry and Biochemistry
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biology Consortium, Beamline 4.2.2, Advanced Light Source
Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH (United States). Research Services ; Departments of Medicine, Pharmacology, Molecular Biology and Microbiology, Biochemistry, Proteomics and Bioinformatics, and the CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology, Cleveland, OH (United States)

Use and misuse of antibiotics have driven the evolution of serine β-lactamases to better recognize new generations of β-lactam drugs, but the selective pressures driving evolution of metallo-β-lactamases are less clear. Here in this paper, we present evidence that New Delhi metallo-β-lactamase (NDM) is evolving to overcome the selective pressure of zinc(II) scarcity. Studies of NDM-1, NDM-4 (M154L), and NDM-12 (M154L, G222D) demonstrate that the point mutant M154L, contained in 50% of clinical NDM variants, selectively enhances resistance to the penam ampicillin at low zinc(II) concentrations relevant to infection sites. Each of the clinical variants is shown to be progressively more thermostable and to bind zinc(II) more tightly than NDM-1, but a selective enhancement of penam turnover at low zinc(II) concentrations indicates that most of the improvement derives from catalysis rather than stability. X-ray crystallography of NDM-4 and NDM-12, as well as bioinorganic spectroscopy of dizinc(II), zinc(II)/cobalt(II), and dicobalt(II) metalloforms probe the mechanism of enhanced resistance and reveal perturbations of the dinuclear metal cluster that underlie improved catalysis. Lastly, these studies support the proposal that zinc(II) scarcity, rather than changes in antibiotic structure, is driving the evolution of new NDM variants in clinical settings.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231; AC03-76SF00098

OSTI ID:: 1426739

Journal Information:: ACS Infectious Diseases, Vol. 3, Issue 12; ISSN 2373-8227

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 38 works

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References (60)

Characterization of a New Metallo- -Lactamase Gene, blaNDM-1, and a Novel Erythromycin Esterase Gene Carried on a Unique Genetic Structure in Klebsiella pneumoniae Sequence Type 14 from India Yong, D.; Toleman, M. A.; Giske, C. G. Antimicrobial Agents and Chemotherapy, Vol. 53, Issue 12 https://doi.org/10.1128/AAC.00774-09	journal	September 2009
NDM-2 carbapenemase in Acinetobacter baumannii from Egypt Kaase, M.; Nordmann, P.; Wichelhaus, T. A. Journal of Antimicrobial Chemotherapy, Vol. 66, Issue 6 https://doi.org/10.1093/jac/dkr135	journal	March 2011
Biochemical Analysis of Metallo-β-Lactamase NDM-3 from a Multidrug-Resistant Escherichia coli Strain Isolated in Japan Tada, Tatsuya; Miyoshi-Akiyama, Tohru; Shimada, Kayo Antimicrobial Agents and Chemotherapy, Vol. 58, Issue 6 https://doi.org/10.1128/AAC.02793-13	journal	March 2014
NDM-4 Metallo-β-Lactamase with Increased Carbapenemase Activity from Escherichia coli Nordmann, Patrice; Boulanger, Anne E.; Poirel, Laurent Antimicrobial Agents and Chemotherapy, Vol. 56, Issue 4 https://doi.org/10.1128/AAC.05961-11	journal	January 2012
A Novel Variant, NDM-5, of the New Delhi Metallo-β-Lactamase in a Multidrug-Resistant Escherichia coli ST648 Isolate Recovered from a Patient in the United Kingdom Hornsey, Michael; Phee, Lynette; Wareham, David W. Antimicrobial Agents and Chemotherapy, Vol. 55, Issue 12 https://doi.org/10.1128/AAC.05108-11	journal	September 2011
Identification and molecular characterisation of New Delhi metallo-β-lactamase-1 (NDM-1)- and NDM-6-producing Enterobacteriaceae from New Zealand hospitals Williamson, Deborah A.; Sidjabat, Hanna E.; Freeman, Joshua T. International Journal of Antimicrobial Agents, Vol. 39, Issue 6 https://doi.org/10.1016/j.ijantimicag.2012.02.017	journal	June 2012
Detection of NDM-7 in Germany, a new variant of the New Delhi metallo- -lactamase with increased carbapenemase activity Gottig, S.; Hamprecht, A. G.; Christ, S. Journal of Antimicrobial Chemotherapy, Vol. 68, Issue 8 https://doi.org/10.1093/jac/dkt088	journal	April 2013
NDM-8 Metallo-β-Lactamase in a Multidrug-Resistant Escherichia coli Strain Isolated in Nepal Tada, Tatsuya; Miyoshi-Akiyama, Tohru; Dahal, Rajan K. Antimicrobial Agents and Chemotherapy, Vol. 57, Issue 5 https://doi.org/10.1128/AAC.02553-12	journal	March 2013
Novel NDM-9 metallo-β-lactamase identified from a ST107 Klebsiella pneumoniae strain isolated in China Wang, Xiaojuan; Li, Henan; Zhao, Chunjiang International Journal of Antimicrobial Agents, Vol. 44, Issue 1 https://doi.org/10.1016/j.ijantimicag.2014.04.010	journal	July 2014
Presence of a novel variant NDM-10, of the New Delhi metallo-beta-lactamase in a Klebsiella pneumoniae isolate Khajuria, Atul; Praharaj, Ashok Kumar; Kumar, Mahadevan Indian Journal of Medical Microbiology, Vol. 34, Issue 1 https://doi.org/10.4103/0255-0857.174101	journal	January 2016
NDM-12, a Novel New Delhi Metallo-β-Lactamase Variant from a Carbapenem-Resistant Escherichia coli Clinical Isolate in Nepal Tada, Tatsuya; Shrestha, Basudha; Miyoshi-Akiyama, Tohru Antimicrobial Agents and Chemotherapy, Vol. 58, Issue 10 https://doi.org/10.1128/AAC.03355-14	journal	August 2014
Identification of a Novel NDM Variant, NDM-13, from a Multidrug-Resistant Escherichia coli Clinical Isolate in Nepal Shrestha, Basudha; Tada, Tatsuya; Miyoshi-Akiyama, Tohru Antimicrobial Agents and Chemotherapy, Vol. 59, Issue 9 https://doi.org/10.1128/AAC.00332-15	journal	July 2015
A Novel New Delhi Metallo-β-Lactamase Variant, NDM-14, Isolated in a Chinese Hospital Possesses Increased Enzymatic Activity against Carbapenems Zou, Dayang; Huang, Yong; Zhao, Xiangna Antimicrobial Agents and Chemotherapy, Vol. 59, Issue 4 https://doi.org/10.1128/AAC.05168-14	journal	February 2015
Multiyear, Multinational Survey of the Incidence and Global Distribution of Metallo-β-Lactamase-Producing Enterobacteriaceae and Pseudomonas aeruginosa Kazmierczak, Krystyna M.; Rabine, Sharon; Hackel, Meredith Antimicrobial Agents and Chemotherapy, Vol. 60, Issue 2 https://doi.org/10.1128/AAC.02379-15	journal	February 2016
Plasmid-Mediated Novel bla _NDM-17 Gene Encoding a Carbapenemase with Enhanced Activity in a Sequence Type 48 Escherichia coli Strain Liu, Zhihai; Wang, Yang; Walsh, Timothy R. Antimicrobial Agents and Chemotherapy, Vol. 61, Issue 5 https://doi.org/10.1128/AAC.02233-16	journal	May 2017
B1-Metallo-β-Lactamases: Where Do We Stand? F. Mojica, Maria; A. Bonomo, Robert; Fast, Walter Current Drug Targets, Vol. 17, Issue 9 https://doi.org/10.2174/1389450116666151001105622	journal	May 2016
Epidemiological Expansion, Structural Studies, and Clinical Challenges of New β-Lactamases from Gram-Negative Bacteria Bush, Karen; Fisher, Jed F. Annual Review of Microbiology, Vol. 65, Issue 1 https://doi.org/10.1146/annurev-micro-090110-102911	journal	October 2011
The Drug-Resistant Variant P167S Expands the Substrate Profile of CTX-M β-Lactamases for Oxyimino-Cephalosporin Antibiotics by Enlarging the Active Site upon Acylation Patel, Meha P.; Hu, Liya; Stojanoski, Vlatko Biochemistry, Vol. 56, Issue 27 https://doi.org/10.1021/acs.biochem.7b00176	journal	June 2017
Biochemical characterization of New Delhi metallo-β-lactamase variants reveals differences in protein stability Makena, Anne; Brem, Jürgen; Pfeffer, Inga Journal of Antimicrobial Chemotherapy, Vol. 70, Issue 2 https://doi.org/10.1093/jac/dku403	journal	October 2014
Transition Metals and Virulence in Bacteria Palmer, Lauren D.; Skaar, Eric P. Annual Review of Genetics, Vol. 50, Issue 1 https://doi.org/10.1146/annurev-genet-120215-035146	journal	November 2016
Microbial Iron Acquisition: Marine and Terrestrial Siderophores Sandy, Moriah; Butler, Alison Chemical Reviews, Vol. 109, Issue 10 https://doi.org/10.1021/cr9002787	journal	October 2009
Nutritional immunity: transition metals at the pathogen–host interface Hood, M. Indriati; Skaar, Eric P. Nature Reviews Microbiology, Vol. 10, Issue 8 https://doi.org/10.1038/nrmicro2836	journal	July 2012
Femtomolar Sensitivity of Metalloregulatory Proteins Controlling Zinc Homeostasis Outten, C. E. Science, Vol. 292, Issue 5526 https://doi.org/10.1126/science.1060331	journal	June 2001
Zn(II) Binding to Escherichia coli 70S Ribosomes Hensley, M. Patrick; Tierney, David L.; Crowder, Michael W. Biochemistry, Vol. 50, Issue 46 https://doi.org/10.1021/bi200619w	journal	November 2011
Beyond iron: non-classical biological functions of bacterial siderophores Johnstone, Timothy C.; Nolan, Elizabeth M. Dalton Transactions, Vol. 44, Issue 14 https://doi.org/10.1039/C4DT03559C	journal	January 2015
Crystal structure of NDM-1 reveals a common β-lactam hydrolysis mechanism Zhang, HongMin; Hao, Quan The FASEB Journal, Vol. 25, Issue 8 https://doi.org/10.1096/fj.11-184036	journal	August 2011
Spectroscopic and Mechanistic Studies of Heterodimetallic Forms of Metallo-β-lactamase NDM-1 Yang, Hao; Aitha, Mahesh; Marts, Amy R. Journal of the American Chemical Society, Vol. 136, Issue 20 https://doi.org/10.1021/ja410376s	journal	May 2014
Flexible Metal Binding of the Metallo-β-lactamase Domain: Glyoxalase II Incorporates Iron, Manganese, and Zinc in Vivo ^† Schilling, Oliver; Wenzel, Nathan; Naylor, Melissa Biochemistry, Vol. 42, Issue 40 https://doi.org/10.1021/bi034672o	journal	October 2003
Metal Content of Metallo-β-lactamase L1 Is Determined by the Bioavailability of Metal Ions Hu, Zhenxin; Gunasekera, Thusitha S.; Spadafora, Lauren Biochemistry, Vol. 47, Issue 30 https://doi.org/10.1021/bi8004768	journal	July 2008
Use of ferrous iron by metallo-β-lactamases Cahill, Samuel T.; Tarhonskaya, Hanna; Rydzik, Anna M. Journal of Inorganic Biochemistry, Vol. 163 https://doi.org/10.1016/j.jinorgbio.2016.07.013	journal	October 2016
Characterization of Purified New Delhi Metallo-β-lactamase-1 Thomas, Pei W.; Zheng, Min; Wu, Shanshan Biochemistry, Vol. 50, Issue 46 https://doi.org/10.1021/bi201449r	journal	November 2011
Sputum zinc concentration and clinical outcome in older asthmatics: Asthma and sputum zinc concentrations Jayaram, Lata; Chunilal, Sanjeev; Pickering, Sandy Respirology, Vol. 16, Issue 3 https://doi.org/10.1111/j.1440-1843.2011.01932.x	journal	March 2011
The Human Urine Metabolome Bouatra, Souhaila; Aziat, Farid; Mandal, Rupasri PLoS ONE, Vol. 8, Issue 9 https://doi.org/10.1371/journal.pone.0073076	journal	September 2013
Sputum Trace Metals Are Biomarkers of Inflammatory and Suppurative Lung Disease Gray, Robert D.; Duncan, Andrew; Noble, Donald Chest, Vol. 137, Issue 3 https://doi.org/10.1378/chest.09-1047	journal	March 2010
Elevated metal concentrations in the CF airway correlate with cellular injury and disease severity Smith, Daniel J.; Anderson, Gregory J.; Bell, Scott C. Journal of Cystic Fibrosis, Vol. 13, Issue 3 https://doi.org/10.1016/j.jcf.2013.12.001	journal	May 2014
Metallo-β-lactamases withstand low Zn(II) conditions by tuning metal-ligand interactions González, Javier M.; Meini, María-Rocío; Tomatis, Pablo E. Nature Chemical Biology, Vol. 8, Issue 8 https://doi.org/10.1038/nchembio.1005	journal	June 2012
Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamase González, Lisandro J.; Bahr, Guillermo; Nakashige, Toshiki G. Nature Chemical Biology, Vol. 12, Issue 7 https://doi.org/10.1038/nchembio.2083	journal	May 2016
Carbonic anhydrase II-based metal ion sensing: Advances and new perspectives Hurst, Tamiika K.; Wang, Da; Thompson, Richard B. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1804, Issue 2 https://doi.org/10.1016/j.bbapap.2009.09.031	journal	February 2010
An altered zinc-binding site confers resistance to a covalent inactivator of New Delhi metallo-beta-lactamase-1 (NDM-1) discovered by high-throughput screening Thomas, Pei W.; Spicer, Timothy; Cammarata, Michael Bioorganic & Medicinal Chemistry, Vol. 21, Issue 11 https://doi.org/10.1016/j.bmc.2013.03.031	journal	June 2013
A chromogenic cephalosporin for β-lactamase inhibitor screening assays Yu, Sophia; Vosbeek, Amy; Corbella, Katherine Analytical Biochemistry, Vol. 428, Issue 2 https://doi.org/10.1016/j.ab.2012.06.006	journal	September 2012
Targeting metallo-carbapenemases via modulation of electronic properties of cephalosporins Yang, Hao; Young, Heather; Yu, Sophia Biochemical Journal, Vol. 464, Issue 2 https://doi.org/10.1042/BJ20140364	journal	November 2014
Substrate-activated Zinc Binding of Metallo-β-lactamases: PHYSIOLOGICAL IMPORTANCE OF THE MONONUCLEAR ENZYMES Wommer, Sandra; Rival, Sandrine; Heinz, Uwe Journal of Biological Chemistry, Vol. 277, Issue 27 https://doi.org/10.1074/jbc.M202467200	journal	April 2002
Metal Content and Localization during Turnover in B. cereus Metallo-β-lactamase Llarrull, Leticia I.; Tioni, Mariana F.; Vila, Alejandro J. Journal of the American Chemical Society, Vol. 130, Issue 47 https://doi.org/10.1021/ja801168r	journal	November 2008
Molar absorption coefficients and stability constants of metal complexes of 4-(2-pyridylazo)resorcinol (PAR): Revisiting common chelating probe for the study of metalloproteins Kocyła, Anna; Pomorski, Adam; Krężel, Artur Journal of Inorganic Biochemistry, Vol. 152 https://doi.org/10.1016/j.jinorgbio.2015.08.024	journal	November 2015
Structural Influence of Hydrophobic Core Residues on Metal Binding and Specificity in Carbonic Anhydrase II ^† ^, ^‡ Cox, J. David; Hunt, Jennifer A.; Compher, Kevin M. Biochemistry, Vol. 39, Issue 45 https://doi.org/10.1021/bi001649j	journal	November 2000
Nuclear magnetic resonance of paramagnetic metalloproteins Bertini, Ivano; Turano, Paola; Vila, Alejandro J. Chemical Reviews, Vol. 93, Issue 8 https://doi.org/10.1021/cr00024a009	journal	December 1993
Trapping and Characterization of a Reaction Intermediate in Carbapenem Hydrolysis by B. cereus Metallo-β-lactamase Tioni, Mariana F.; Llarrull, Leticia I.; Poeylaut-Palena, Andrés A. Journal of the American Chemical Society, Vol. 130, Issue 47 https://doi.org/10.1021/ja801169j	journal	November 2008
Efficacies of calcium–EDTA in combination with imipenem in a murine model of sepsis caused by Escherichia coli with NDM-1 β-lactamase Yoshizumi, Ayumi; Ishii, Yoshikazu; Kimura, Soichiro Journal of Infection and Chemotherapy, Vol. 19, Issue 5 https://doi.org/10.1007/s10156-012-0528-y	journal	January 2013
Aspergillomarasmine A overcomes metallo-β-lactamase antibiotic resistance King, Andrew M.; Reid-Yu, Sarah A.; Wang, Wenliang Nature, Vol. 510, Issue 7506 https://doi.org/10.1038/nature13445	journal	June 2014
Crystal structure of New Delhi metallo-β-lactamase reveals molecular basis for antibiotic resistance King, Dustin; Strynadka, Natalie Protein Science, Vol. 20, Issue 9 https://doi.org/10.1002/pro.697	journal	August 2011
The Role of Residue 238 of TEM-1 β-Lactamase in the Hydrolysis of Extended-spectrum Antibiotics Cantu, Carlos; Palzkill, Timothy Journal of Biological Chemistry, Vol. 273, Issue 41 https://doi.org/10.1074/jbc.273.41.26603	journal	October 1998
Early Dissemination of NDM-1- and OXA-181-Producing Enterobacteriaceae in Indian Hospitals: Report from the SENTRY Antimicrobial Surveillance Program, 2006-2007 Castanheira, Mariana; Deshpande, Lalitagauri M.; Mathai, Dilip Antimicrobial Agents and Chemotherapy, Vol. 55, Issue 3 https://doi.org/10.1128/AAC.01497-10	journal	December 2010
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
Optimal description of a protein structure in terms of multiple groups undergoing TLS motion Painter, Jay; Merritt, Ethan A. Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 4 https://doi.org/10.1107/S0907444906005270	journal	March 2006
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
Frequency-Switching Inversion-Recovery for Severely Hyperfine-Shifted NMR: Evidence of Asymmetric Electron Relaxation in High-Spin Co(II) Riley, Erin A.; Petros, Amy K.; Smith, Karen Ann Inorganic Chemistry, Vol. 45, Issue 25 https://doi.org/10.1021/ic061207h	journal	November 2006
New Delhi Metallo-β-Lactamase: Structural Insights into β-Lactam Recognition and Inhibition King, Dustin T.; Worrall, Liam J.; Gruninger, Robert Journal of the American Chemical Society, Vol. 134, Issue 28 https://doi.org/10.1021/ja303579d	journal	July 2012
Polder maps: improving OMIT maps by excluding bulk solvent Liebschner, Dorothee; Afonine, Pavel V.; Moriarty, Nigel W. Acta Crystallographica Section D Structural Biology, Vol. 73, Issue 2, p. 148-157 https://doi.org/10.1107/S2059798316018210	journal	February 2017

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