Journal ArticleDOI
Metallo-β-lactamases in the Age of Multidrug Resistance: From Structure and Mechanism to Evolution, Dissemination, and Inhibitor Design.
TLDR
In this article, a review of the active site and catalytic mechanism of Metallo-β-lactamases (MBLs) is presented, and the success of MBLs in conferring resistance to carbapenems, penicillins, and cephalosporins.Abstract:
Antimicrobial resistance is one of the major problems in current practical medicine. The spread of genes coding for resistance determinants among bacteria challenges the use of approved antibiotics, narrowing the options for treatment. Resistance to carbapenems, last resort antibiotics, is a major concern. Metallo-β-lactamases (MBLs) hydrolyze carbapenems, penicillins, and cephalosporins, becoming central to this problem. These enzymes diverge with respect to serine-β-lactamases by exhibiting a different fold, active site, and catalytic features. Elucidating their catalytic mechanism has been a big challenge in the field that has limited the development of useful inhibitors. This review covers exhaustively the details of the active-site chemistries, the diversity of MBL alleles, the catalytic mechanism against different substrates, and how this information has helped developing inhibitors. We also discuss here different aspects critical to understand the success of MBLs in conferring resistance: the molecular determinants of their dissemination, their cell physiology, from the biogenesis to the processing involved in the transit to the periplasm, and the uptake of the Zn(II) ions upon metal starvation conditions, such as those encountered during an infection. In this regard, the chemical, biochemical and microbiological aspects provide an integrative view of the current knowledge of MBLs.read more
Citations
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Journal ArticleDOI
Development of peptide-based metallo-β-lactamase inhibitors as new strategy to combat antimicrobial resistance: A Mini-review.
TL;DR: How traditional computational tools such as in silico screening and molecular docking, along with new methods such as deep learning and machine learning, enable design of peptide-based inhibitors of MBLs designs more accurate and efficient are discussed.
Journal ArticleDOI
Structural Insights for Core Scaffold and Substrate Specificity of B1, B2, and B3 Metallo-β-Lactamases
Yeon Kyoung Yun,Sang Chan Han,Yoon Sik Park,Hyunjae Park,Dogyeong Kim,Ye-Seul Kim,Yong-Jae Kwon,Sumin Kim,Jung Hun Lee,Jeong Ho Jeon,Sang Hee Lee,Lin-Woo Kang +11 more
TL;DR: In this article , the core scaffold, the zinc-coordinating residues in the active site, and the substrate-binding pocket of metallo-β-lactamases are compared.
Journal ArticleDOI
Novel Antimicrobial Agents for Gram-Negative Pathogens
Marios Karvouniaris,Maria-Panagiota Almyroudi,Mohd H. Abdul-Aziz,Stijn Blot,Elisabeth Paramythiotou,E. Tsigou,Despoina Koulenti +6 more
TL;DR: A review of the characteristics of the above-mentioned antimicrobials, their pharmacokinetic/pharmacodynamic properties and the current clinical data is presented in this paper , where the authors critically discuss the characteristics and characteristics of these agents.
Journal ArticleDOI
Two‐Step Validation Approach for Tools To Study the DNA Repair Enzyme SNM1A
Ellen M Fay,Ailish Newton,Mark Christopher Berney,Afaf H. El-Sagheer,Tom Brown,Joanna F. McGouran +5 more
TL;DR: In this paper , a two-step validation approach was used to evaluate the suitability of metal-binding groups for targeting DNA damage-repair metalloenzymes using model enzyme SNM1A.
Journal ArticleDOI
Design, Synthesis, and Biological Evaluation of New 1H-Imidazole-2-Carboxylic Acid Derivatives as Metallo-β-Lactamase Inhibitors.
Rong Li,Huilin Su,Wei Chen,Yu-Hang Yan,Cong Zhou,Luo Mou,Huanming Yang,Shan Qian,Zhouyu Wang,Lingling Yang,Guo-Bo Li +10 more
TL;DR: In this article , structural optimization of 1H-imidazole-2-carboxylic acid and substituents was performed to combat metallo-β-lactamases (MBLs) resistant to antimicrobial resistance.
References
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Journal ArticleDOI
Loop-mediated isothermal amplification of DNA
Tsugunori Notomi,Hiroto Okayama,Harumi Otawara-shi Masubuchi,Toshihiro Yonekawa,Keiko Watanabe,Nobuyuki Amino,Tetsu Hase +6 more
TL;DR: A novel method that amplifies DNA with high specificity, efficiency and rapidity under isothermal conditions that employs a DNA polymerase and a set of four specially designed primers that recognize a total of six distinct sequences on the target DNA.
Journal ArticleDOI
Molecular Basis of Bacterial Outer Membrane Permeability Revisited
TL;DR: This review summarizes the development in the field since the previous review and begins to understand how this bilayer of the outer membrane can retard the entry of lipophilic compounds, owing to increasing knowledge about the chemistry of lipopolysaccharide from diverse organisms and the way in which lipopoly Saccharide structure is modified by environmental conditions.
Journal ArticleDOI
SignalP 5.0 improves signal peptide predictions using deep neural networks
Jose Juan Almagro Armenteros,Konstantinos D. Tsirigos,Casper Kaae Sønderby,Thomas Nordahl Petersen,Ole Winther,Ole Winther,Søren Brunak,Søren Brunak,Gunnar von Heijne,Gunnar von Heijne,Henrik Nielsen +10 more
TL;DR: A deep neural network-based approach that improves SP prediction across all domains of life and distinguishes between three types of prokaryotic SPs is presented.
Journal ArticleDOI
A functional classification scheme for beta-lactamases and its correlation with molecular structure.
TL;DR: These enzymes are the major cause of bacterial resistance to b-lactam antibiotics and have been the subject of extensive microbiological, biochemical, and genetic investigations.
Journal ArticleDOI
Characterization of a New Metallo-β-Lactamase Gene, blaNDM-1, and a Novel Erythromycin Esterase Gene Carried on a Unique Genetic Structure in Klebsiella pneumoniae Sequence Type 14 from India
Dongeun Yong,Mark Toleman,Christian G. Giske,Hyun Sun Cho,Kristina Sundman,Kyungwon Lee,Timothy R. Walsh +6 more
TL;DR: A Swedish patient of Indian origin traveled to New Delhi, India, and acquired a urinary tract infection caused by a carbapenem-resistant Klebsiella pneumoniae strain that typed to the sequence type 14 complex, showing broad resistance carried on these plasmids.