Article
Microbiology
Christophe Le Terrier, Clement Viguier, Patrice Nordmann, Alejandro J. Vila, Laurent Poirel
Summary: Taniborbactam showed excellent activity against B1 MBLs, except for SIM-1. VIM-1-like enzymes, particularly VIM-83, were less inhibited by Taniborbactam compared to VIM-2-like.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Chemistry, Multidisciplinary
Wen Bin Jin, Chen Xu, Xiao Lin Qi, Ping Zeng, Wei Gao, Ki Hon Lai, Jiachi Chiou, Edward W. C. Chan, Yun-Chung Leung, Tak Hang Chan, Kwok-Yin Wong, Sheng Chen, Kin-Fai Chan
Summary: Efficient construction of a series of trans-1,3,4-trisubstituted pyrrolidines via boric acid-catalyzed 1,3-dipolar cycloaddition for biological evaluation against NDM-1 positive carbapenem-resistant Enterobacteriaceae. Compound 10e showed low cytotoxicity, moderate NDM-1 enzyme inhibition, and potent synergistic activity against clinically isolated NDM-1 positive CRE, suggesting it as a promising starting point for carbapenem antibiotic adjuvants.
NEW JOURNAL OF CHEMISTRY
(2021)
Article
Infectious Diseases
P. Urbanowicz, R. Izdebski, A. Baraniak, D. Zabicka, W. Hryniewicz, M. Gniadkowski
Summary: This study identified the molecular and genomic background of the rapid increase of MPPA in Poland, with multi-clonal spread as the leading factor. Various novel and specific characteristics of MPPA were also revealed through the analysis.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Chemistry, Medicinal
Yue-Juan Zhang, Le Zhai, Yi Wan, Ke-Wu Yang
Summary: A series of triazolylthioacetamides were synthesized and exhibited specific inhibitory activity against IMP-1, potentially enhancing the antibacterial efficacy of cefazolin. Some compounds showed low cytotoxicity in cell assays. These findings indicate that triazolylthioacetamides could serve as effective inhibitors of metallo-beta-lactamases.
LETTERS IN DRUG DESIGN & DISCOVERY
(2021)
Article
Chemistry, Multidisciplinary
Katarzyna Palica, Manuela Voracova, Susann Skagseth, Anna Andersson Rasmussen, Lisa Allander, Madlen Hubert, Linus Sandegren, Hanna-Kirstirep Schroder Leiros, Hanna Andersson, Mate Erdelyi
Summary: Infectious diseases remain a major concern for public health in the 21st century, and the development of antimicrobial resistance by microbes is a significant problem. The study found that phosphonamidate compounds have the potential to become a new generation of antibiotic therapeutics to combat metallo-beta-lactamase-resistant bacteria.
Article
Microbiology
Magdalena Zalacain, Clarisse Lozano, Agustina Llanos, Nicolas Sprynski, Thomas Valmont, Cyntia De Piano, David Davies, Simon Leiris, Carole Sable, Adeline Ledoux, Ian Morrissey, Marc Lemonnier, Martin Everett
Summary: The global dissemination of metallo-beta-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE) is a serious public health concern, with NDM (New Delhi MBL) being a major cause of carbapenem therapy failures and limited treatment options due to additional resistance determinants carried on promiscuous plasmids encoding the NDM gene. ANT2681, a specific MBL inhibitor, shows potent activity against NDM enzymes and offers a potential new therapeutic option to treat serious infections caused by NDM-CRE.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Chemistry, Multidisciplinary
Jurgen Brem, Tharindi Panduwawala, Jon Ulf Hansen, Joanne Hewitt, Edgars Liepins, Pawel Donets, Laura Espina, Alistair J. M. Farley, Kirill Shubin, Gonzalo Gomez Campillos, Paula Kiuru, Shifali Shishodia, Daniel Krahn, Robert K. Lesniak, Juliane Schmidt (Adrian), Karina Calvopina, Maria-Carmen Turrientes, Madeline E. Kavanagh, Dmitrijs Lubriks, Philip Hinchliffe, Gareth W. Langley, Ali F. Aboklaish, Anders Eneroth, Maria Backlund, Andrei G. Baran, Elisabet Nielsen, Michael Speake, Janis Kuka, John Robinson, Solveiga Grinberga, Lindsay Robinson, Michael A. McDonough, Anna M. Rydzik, Thomas M. Leissing, Juan Carlos Jimenez-Castellanos, Matthew B. Avison, Solange Da Silva Pinto, Andrew D. Pannifer, Marina Martjuga, Emma Widlake, Martins Priede, Iva Hopkins Navratilova, Marek Gniadkowski, Anna Karin Belfrage, Peter Brandt, Jari Yli-Kauhaluoma, Eric Bacque, Malcolm G. P. Page, Fredrik Bjorkling, Jonathan M. Tyrrell, James Spencer, Pauline A. Lang, Pawel Baranczewski, Rafael Canton, Stuart P. McElroy, Philip S. Jones, Fernando Baquero, Edgars Suna, Angus Morrison, Timothy R. Walsh, Christopher J. Schofield
Summary: The discovery of a potent new class of MBL inhibitor, InCs, restores carbapenem activity against multidrug-resistant bacteria with low resistance frequency. In combination with meropenem, InCs show strong in vivo efficacy in mouse infection models.
Article
Biochemistry & Molecular Biology
Akari Ikeda, Yoshiki Ikegaya, Masako Honsho, Hidehito Matsui, Kenichi Nonaka, Takahiro Ishii, Yukihiro Asami, Hideaki Hanaki, Tomoyasu Hirose, Toshiaki Sunazuka
Summary: 3Z,5E-Octa-3,5-diene-1,3,4-tricarboxylic acid-3,4-anhydride (ODTAA, 1) was isolated from Paecilomyces sp. FKI-6801 for its selective IMP-1 MBL inhibitory activity. The total synthesis of 1 was achieved from commercially available compound in 9 steps with 28% overall yield. Introduction of catechol to the maleic anhydride of 1 improved the IC50 towards IMP-1 MBL and the inhibitory activity against IMP-1 MBL-producing P. aeruginosa. Treatment of the maleic anhydride scaffold with amine revealed the beta-carbonyl-alpha,beta-unsaturated carboxylic acid moiety as a pharmacophore for IMP-1 MBL inhibition.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Nenad Macesic, Jane Hawkey, Ben Vezina, Jessica A. Wisniewski, Hugh Cottingham, Luke V. Blakeway, Taylor Harshegyi, Katherine Pragastis, Gnei Zweena Badoordeen, Amanda Dennison, Denis W. Spelman, Adam W. J. Jenney, Anton Y. Peleg
Summary: Infections caused by metallo-beta-lactamase-producing organisms (MBLs) are a global health threat. This study analysed the evolution and transmission dynamics of the bla(IMP-4) gene over two decades in a hospital, providing a framework for understanding the endemicity and spread of MBLs.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Liqiang Hu, Huixin Yang, Tao Yu, Fangfang Chen, Runqiu Liu, Shuyuan Xue, Shuangzhan Zhang, Wuyu Mao, Changge Ji, Hao Wang, Hexin Xie
Summary: This study demonstrates the effectiveness of stereochemically altered cephalosporins as potent inhibitors against NDM-1, a major cause of antibiotic resistance. The findings provide a new approach to combat antibiotic resistance.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Luana La Piana, Valentina Viaggi, Luigi Principe, Stefano Di Bella, Francesco Luzzaro, Maurizio Viale, Nadia Bertola, Graziella Vecchio
Summary: Bacteria have developed resistance mechanisms against common antibiotics, with zinc-dependent metallo-beta-lactamase producing bacteria posing a growing threat. Zinc chelators have been studied as inhibitors to restore antibiotic susceptibility, showing promising results in experimental studies with various synthetic polypyridyl ligands.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2021)
Article
Infectious Diseases
Nobuyoshi Mori, Tatsuya Tada, Satoshi Oshiro, Kyoko Kuwahara-Arai, Teruo Kirikae, Yuki Uehara
Summary: This study described a patient infected with three species of CPE carrying an identical transferrable IncL/M plasmid. The research found that these three species of CPE in the patient could transfer plasmids to each other, with Serratia marcescens able to transmit the plasmid to Enterobacter cloacae and Klebsiella aerogenes.
BMC INFECTIOUS DISEASES
(2021)
Article
Multidisciplinary Sciences
M. Wilamowski, D. A. Sherrell, Y. Kim, A. Lavens, R. W. Henning, K. Lazarski, A. Shigemoto, M. Endres, N. Maltseva, G. Babnigg, S. C. Burdette, V. Srajer, A. Joachimiak
Summary: Serial x-ray crystallography can reveal binding events and chemical conversions during enzymatic reactions. This study used time-resolved serial synchrotron crystallography to analyze the structure, binding, and cleavage of moxalactam antibiotic in L1 metallo-beta-lactamase from Stenotrophomonas maltophilia.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Fangfang Chen, Mengmeng Bai, Wentian Liu, Hongtao Kong, Tingting Zhang, Hong Yao, En Zhang, Juan Du, Shangshang Qin
Summary: Metallo-beta-lactamases (MBLs) are a significant public health concern due to limited treatment options, and there is currently no available MBL inhibitor in clinical practice. This study synthesized a series of H(2)dpa derivatives and evaluated their inhibitory activity against clinically relevant MBLs, demonstrating potent synergistic activity and restored efficacy against MBL-producing Enterobacterales and Pseudomonas aeruginosa. Compounds 5b and 5c were found to be non-competitive MBL inhibitors, showing increased survival rates in sepsis mice models caused by NDM-1-positive strains. The results suggest that these compounds containing pentadentate-chelating ligands are promising for further study.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Infectious Diseases
Tushar Kumar Dey, Johanna Frida Lindahl, Ake Lundkvist, Delia Grace, Ram Pratim Deka, Rajeswari Shome, Samiran Bandyopadhyay, Naresh Kumar Goyal, Garima Sharma, Bibek Ranjan Shome
Summary: This study investigated the prevalence of beta-lactamase-producing Enterobacteriaceae in milk samples from two Indian states, revealing the presence of various prevalent beta-lactamase genes. The findings underscore the potential risk of antimicrobial-resistant bacteria in dairy products and the need for comprehensive approaches to accurately assess antibiotic resistance.
Article
Chemistry, Medicinal
Alexander Bergstrom, Andrew Katko, Zach Adkins, Jessica Hill, Zishuo Cheng, Mia Burnett, Hao Yang, Mahesh Aitha, M. Rachel Mehaffey, Jennifer S. Brodbelt, Kamaleddin H. M. E. Tehrani, Nathaniel I. Martin, Robert A. Bonomo, Richard C. Page, David L. Tierney, Walter Fast, Gerard D. Wright, Michael W. Crowder
ACS INFECTIOUS DISEASES
(2018)
Article
Chemistry, Multidisciplinary
Amanda S. Byer, Hao Yang, Elizabeth C. McDaniel, Venkatesan Kathiresan, Stella Impano, Adrien Pagnier, Hope Watts, Carly Denler, Anna L. Vagstad, Jorn Piel, Kaitlin S. Duschene, Eric M. Shepard, Thomas P. Shields, Lincoln G. Scott, Edward A. Lilla, Kenichi Yokoyama, William E. Broderick, Brian M. Hoffman, Joan B. Broderick
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2018)
Article
Chemistry, Inorganic & Nuclear
Hao Yang, Jonathan Rittle, Amy R. Marts, Jonas C. Peters, Brian M. Hoffman
INORGANIC CHEMISTRY
(2018)
Article
Chemistry, Multidisciplinary
Hao Yang, Elizabeth C. McDaniel, Stella Impano, Amanda S. Byer, Richard J. Jodts, Kenichi Yokoyama, William E. Broderick, Joan B. Broderick, Brian M. Hoffman
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2019)
Article
Chemistry, Multidisciplinary
Hao Yang, Stella Impano, Eric M. Shepard, Christopher D. James, William E. Broderick, Joan B. Broderick, Brian M. Hoffman
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2019)
Article
Chemistry, Multidisciplinary
Adrien Pagnier, Hao Yang, Richard J. Jodts, Christopher D. James, Eric M. Shepard, Stella Impano, William E. Broderick, Brian M. Hoffman, Joan B. Broderick
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2020)
Article
Chemistry, Multidisciplinary
Stella Impano, Hao Yang, Eric M. Shepard, Ryan Swimley, Adrien Pagnier, William E. Broderick, Brian M. Hoffman, Joan B. Broderick
Summary: Research demonstrates that S-adenosyl-l-ethionine (SAE) can serve as an alternative to SAM in supporting the enzymatic turnover of HydG and forming organometallic intermediates. Photolysis of SAE-bound HydG results in the formation of an ethyl radical that can be stored at low temperatures for extended periods. The ethyl radical, when heated above 77 K, adds to the [4Fe-4S](2+) cluster, generating an ethyl-[4Fe-4S](3+) organometallic species.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Stella Impano, Hao Yang, Richard J. Jodts, Adrien Pagnier, Ryan Swimley, Elizabeth C. McDaniel, Eric M. Shepard, William E. Broderick, Joan B. Broderick, Brian M. Hoffman
Summary: Research has found that typical RS enzymes exhibit two types of S-C bond cleavage under light-induced conditions, depending on ribose conformation rather than the position of the sulfonium center relative to the [4Fe-4S] cluster. Additionally, the cleavage of the S-C bond results in selective cleavage, leading to the generation of radicals.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Juan A. Valdez-Moreira, Daniel M. Beagan, Hao Yang, Joshua Telser, Brian M. Hoffman, Maren Pink, Veronica Carta, Jeremy M. Smith
Summary: The study characterized a thermally stable iron(III) oxo complex and analyzed its structure, spectroscopic, and computational properties. The complex has an unusually short iron-oxygen bond length and is able to perform hydrocarbon oxidations.
ACS CENTRAL SCIENCE
(2021)
Article
Physics, Atomic, Molecular & Chemical
Abigail L. Schroeter, Hao Yang, Christopher D. James, Brian M. Hoffman, Peter E. Doan
Summary: The study characterizes the kinetics of EDTA transfer from Calcium(II) to Copper(II) in imidazole buffers near neutral pH, using stopped-flow absorption spectroscopy and as a tool for calibrating freeze-quench time in a rapid freeze-quench apparatus. The results provide a precise and accurate method for determining t(Q) and are more preferable than using toxic azide solutions for calibration.
APPLIED MAGNETIC RESONANCE
(2022)
Article
Chemistry, Multidisciplinary
Adrien Pagnier, Batuhan Balci, Eric M. Shepard, Hao Yang, Douglas M. Warui, Stella Impano, Squire J. Booker, Brian M. Hoffman, William E. Broderick, Joan B. Broderick
Summary: This study reports the successful maturation of [FeFe]-hydrogenase using a fully defined system without the need for cell lysate. It reveals an essential role for a protein in the glycine cleavage system in hydrogenase maturation and the synthesis of the DTMA ligand. Additionally, it demonstrates that ammonia is the source of the bridgehead nitrogen of DTMA.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Maike N. Lundahl, Raymond Sarksian, Hao Yang, Richard J. Jodts, Adrien Pagnier, Donald F. Smith, Martin A. Mosquera, Wilfred A. van der Donk, Brian M. Hoffman, William E. Broderick, Joan B. Broderick
Summary: Using freeze-quench techniques and electron paramagnetic resonance (EPR) spectroscopy, the reaction pathway of an adenosylation reaction catalyzed by the radical SAM enzyme is studied. The results provide snapshots of the process, revealing the formation of organic intermediate Omega and the generation of 5'-deoxyadenosyl radical and adenosylated peptide radical. These findings help to understand the mechanism of the reaction.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Zhi-Yong Yang, Emilio Jimenez-Vicente, Hayden Kallas, Dmitriy A. Lukoyanov, Hao Yang, Julia S. Martin del Campo, Dennis R. Dean, Brian M. Hoffman, Lance C. Seefeldt
Summary: In this study, the electronic structure of the FeV-cofactor was investigated using genetic, biochemical, and spectroscopic techniques. The findings suggest that the resting state of the FeV-cofactor may be diamagnetic or non-Kramers integer-spin, rather than previously believed to be in a Kramers state. Furthermore, a new rhombic S = 1/2 EPR signal was observed during high-flux turnover, indicating a different assignment for the electronic structure of the FeV-cofactor's resting state.
Article
Multidisciplinary Sciences
Jorge L. Martinez, Sean A. Lutz, Hao Yang, Jiaze Xie, Joshua Telser, Brian M. Hoffman, Veronica Carta, Maren Pink, Yaroslav Losovyj, Jeremy M. Smith
Meeting Abstract
Chemistry, Multidisciplinary
Elizabeth McDaniel, Hao Yang, Amanda Byer, William Broderick, Kenichi Yokoyama, Brian Hoffman, Joan Broderick
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
(2019)