Article
Biochemistry & Molecular Biology
Vidhu Agarwal, Tara Chand Yadav, Akhilesh Tiwari, Pritish Varadwaj
Summary: Antimicrobial resistance is a growing global health challenge. Bacterial infections have developed resistance against beta-lactam antibiotics through various mechanisms, including the production of novel beta-lactamase enzymes. These bacteria have also developed resistance against beta-lactamase inhibitors. Investigating the role of important residues in altering and expanding the spectrum activity of these enzymes is necessary to understand beta-lactamase-mediated resistance.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Ilona van Alen, Aleksandra Chikunova, Danny B. van Zanten, Amber A. de Block, Monika Timmer, Steffen Brunle, Marcellus Ubbink
Summary: Conserved residues are usually essential for protein function, but mutations in highly conserved residues of BlaC did not significantly affect the enzyme. One mutation, D179N, even increased ceftazidime resistance while maintaining good activity against penicillins. Crystal structures of BlaC D179N revealed minor structural changes compared to wild-type BlaC, and introducing this mutation in other beta-lactamases resulted in decreased antibiotic resistance. The importance of the interaction with Arg164 explains why Asp179 is not essential in BlaC.
Article
Biochemistry & Molecular Biology
Aleksandra Chikunova, Marcellus Ubbink
Summary: Evolution minimizes the number of highly conserved amino acid residues in proteins to ensure evolutionary robustness and adaptability. This study analyzes the roles of all highly conserved, non-catalytic residues in class A beta-lactamase and reveals their importance in fine-tuning the active site structure, maintaining protein folding and stability.
Article
Biochemistry & Molecular Biology
Wanki Yoo, Ying Wang, Sangeun Jeon, Han-Woo Kim, Ly Thi Huong Luu Le, Kyeong Kyu Kim, T. Doohun Kim
Summary: A novel bifunctional enzyme called LgLacI was cloned from Lactococcus garvieae. LgLacI is capable of hydrolyzing various beta-lactam-containing antibiotics and synthesizing biodiesels. The catalytic properties of LgLacI were explored using multiple biochemical methods, and its ability to hydrolyze both esters and beta-lactam antibiotics was confirmed.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Microbiology
Hongyan Luo, Mengru Li, Zhishuang Yang, Dekang Zhu, Pei Li
Summary: A novel chromosomally-located beta-lactamase gene, bla(RASA-1), was identified in Riemerella anatipestifer RA-CH-1. The encoded RASA-1 is a class A extended-spectrum beta-lactamase (ESBL) that confers broad resistance to beta-lactams.
VETERINARY MICROBIOLOGY
(2022)
Article
Infectious Diseases
Camille Gonzalez, Herve Volland, Saoussen Oueslati, Lea Niol, Camille Legrand, Laura Francius, Arnaud Chalin, Anais Vogel, Stephanie Simon, Thierry Naas
Summary: A LFIA prototype has been developed and evaluated for the rapid and reliable detection of GES-type beta-lactamases. The method is efficient, rapid, and easy to implement, making it suitable for confirmation of GES-type beta-lactamases in clinical microbiology laboratories.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Infectious Diseases
Scott A. Becka, Elise T. Zeiser, John J. LiPuma, Krisztina M. Papp-Wallace
Summary: This study evaluated the antimicrobial activity of Tebipenem against multiple strains of Enterobacterales pathogens. The results showed that all strains of Burkholderia cepacia complex (Bcc) and Burkholderia gladioli tested were resistant to Tebipenem. Further experiments revealed that the resistance may be related to the inducible beta-lactamases PenA and AmpC produced by these strains.
Article
Microbiology
Liam A. Wilson, Esmee G. Knaven, Marc T. Morris, Marcelo Monteiro Pedroso, Christopher J. Schofield, Thomas B. Brueck, Mikael Boden, David W. Waite, Philip Hugenholtz, Luke Guddat, Gerhard Schenk
Summary: The study investigates a fourth variant of metallo-beta-lactamase, SIE-1, which shows higher activity towards cephalosporins. The unusual preference of SIE-1 for cephalosporins and its presence in a widespread environmental organism suggest the potential for increased MBL-mediated beta-lactam resistance. Including SIE-1 in MBL inhibitor design studies could expand the therapeutic scope of much needed antiresistance drugs.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Hongyan Luo, Dekang Zhu, Mengru Li, Yunhan Tang, Wenyu Zhang, Haoju Wang, Pei Li
Summary: Whole-genome sequencing of Riemerella anatipestifer isolate RCAD0122 identified a novel ESBL gene, bla(RAA-1), which encoded a class A extended-spectrum beta-lactamase with low sequence identity to known beta-lactamases. The purified RAA-1 showed ESBL-like hydrolysis activity, and the gene could be transferred to a homologous strain through natural transformation. However, epidemiological study revealed the gene is not currently prevalent.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Alessandra Piccirilli, Alberto Antonelli, Marco Maria D'Andrea, Sabrina Cherubini, Mariagrazia Perilli, Gian Maria Rossolini
Summary: The MOX lineage of beta-lactamases includes enzymes encoded by genes mobilized from the chromosomes of Aeromonas spp. to plasmids. MOX-9, a novel sublineage of MOX enzymes, shows a strong preference for cephalosporin substrates with some differences in biochemical characteristics compared to other MOX enzymes.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Alessandra Piccirilli, Sabrina Cherubini, Giuseppe Celenza, Gian Maria Rossolini, Fabrizia Brisdelli, Bernardetta Segatore, Luigi Principe, Francesco Luzzaro, Lilia Andriani, Gianfranco Amicosante, Mariagrazia Perilli
Summary: KPC-53 enzyme is a natural variant of KPC with a duplication of L167E168 residues, which results in decreased stability and significant reductions in activity against beta-lactam antibiotics, particularly carbapenems. The enzyme is susceptible to tazobactam and clavulanic acid but remains resistant to avibactam. Molecular modeling shows that the duplication in KPC-53 alters the interactions between residues involved in catalysis, impacting enzyme flexibility and activity.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
M. Trent Kemp, Derek A. Nichols, Xiujun Zhang, Kyle Defrees, Insung Na, Adam R. Renslo, Yu Chen
Summary: The study characterized the function of the Asp233-Asp246 pair in Class A beta-lactamases using CTX-M-14 beta-lactamase. The D233N mutation led to decreased activity depending on the substrate, while also reducing the binding of a reversible inhibitor. Structural analysis revealed changes in loop movement and hydrogen bond loss, highlighting the importance of the aspartate pair in substrate hydrolysis and suggesting increased protein flexibility as a means to evolve drug resistance.
Article
Chemistry, Multidisciplinary
Matthijs J. van Haren, Kamaleddin H. M. E. Tehrani, Ioli Kotsogianni, Nicola Wade, Nora C. Bruchle, Vida Mashayekhi, Nathaniel I. Martin
Summary: The increasing prevalence of metallo-beta-lactamase (MBL)-expressing bacteria is a worrying trend in antibiotic resistance. Studies have shown that zinc ions, which are essential for the hydrolytic activity of MBLs, can be targeted for inhibition. Researchers have developed a series of cephalosporin prodrugs that exhibit potent activity against MBLs and can act synergistically with specific antibiotics.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Biochemical Research Methods
Vitaly G. Grigorenko, Tatiana E. Petrova, Ciaran Carolan, Maya Yu Rubtsova, Igor Uporov, Joana Pereira, Grzegorz Chojnowski, Valeriya R. Samygina, Victor S. Lamzin, Alexey M. Egorov
Summary: This study presents novel crystal structures of the native beta-lactamase TEM-171 and its complexes with the inhibitor tazobactam. The results provide valuable insights for the rational design of new beta-lactamase inhibitors.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2022)
Review
Cell Biology
Ping-Chieh Pao, Li-Huei Tsai
Summary: Cdk5 is a proline-directed serine/threonine protein kinase that regulates various cellular processes in neurons, and its dysregulation can compromise normal brain function. Researchers have been focusing on the mechanisms and effects of Cdk5 on the nervous system for nearly three decades, with recent findings highlighting its role in neuronal/synaptic functions. Evidence suggests that aberrant Cdk5 activity is a common theme observed in many neurodegenerative diseases.
JOURNAL OF BIOMEDICAL SCIENCE
(2021)
Article
Chemistry, Organic
Mijoon Lee, Tomas Ruci, Dusan Hesek, Allen G. Oliver, Jed F. Fisher, Shahriar Mobashery
JOURNAL OF ORGANIC CHEMISTRY
(2015)
Article
Chemistry, Multidisciplinary
Jennifer Fishovitz, Negin Taghizadeh, Jed F. Fisher, Mayland Chang, Shahriar Mobashery
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2015)
Article
Chemistry, Medicinal
Erika Leemans, Kiran V. Mahasenan, Malika Kumarasiri, Edward Spink, Derong Ding, Peter I. O'Daniel, Marc A. Boudreau, Elena Lastochkin, Sebastian A. Testero, Takao Yamaguchi, Mijoon Lee, Dusan Hesek, Jed F. Fisher, Mayland Chang, Shahriar Mobashery
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2016)
Article
Chemistry, Organic
Julia M. Clay, Dusan Hesek, Allen G. Oliver, Mijoon Lee, Jed F. Fisher
JOURNAL OF ORGANIC CHEMISTRY
(2016)
Article
Biochemistry & Molecular Biology
Teresa Dominguez-Gil, Mijoon Lee, Ivan Acebron-Avalos, Kiran V. Mahasenan, Dusan Hesek, David A. Dik, Byungjin Byun, Elena Lastochkin, Jed F. Fisher, Shahriar Mobashery, Juan A. Hermoso
Review
Biochemistry & Molecular Biology
Jed F. Fisher, Shahriar Mobashery
Article
Medicine, Research & Experimental
Jed F. Fisher, Shahriar Mobashery
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
(2016)
Article
Chemistry, Medicinal
Shusuke Tomoshige, David A. Dik, Masaaki Akabane-Nakata, Chinedu S. Madukoma, Jed F. Fisher, Joshua D. Shrout, Shahriar Mobashery
ACS INFECTIOUS DISEASES
(2018)
Correction
Biochemistry & Molecular Biology
Jed F. Fisher, Shahriar Mobashery
BIOORGANIC CHEMISTRY
(2014)
Article
Chemistry, Multidisciplinary
Mijoon Lee, Dusan Hesek, Bias Blazquez, Elena Lastochkin, Bill Boggess, Jed F. Fisher, Shahriar Mobashery
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2015)
Article
Biochemistry & Molecular Biology
David A. Dik, Choon Kim, Chinedu S. Madukoma, Jed F. Fisher, Joshua D. Shrout, Shahriar Mobashery
ACS CHEMICAL BIOLOGY
(2020)
Review
Chemistry, Multidisciplinary
Jed F. Fisher, Shahriar Mobashery
Summary: The diversity of unicellular bacteria can rival or even exceed that of multicellular eukaryotes in terms of shape, food, metabolism, and ecological niche. The relationship between bacteria that occupy the ecological niche of eukaryotes and eukaryotes is often symbiotic or balanced, but some bacteria, like Staphylococcus aureus, seek advantage in this relationship. Over time, S. aureus has developed resistance mechanisms against beta-lactam antibiotics, requiring the development of new generations of these antibiotics to counteract this resistance.
Review
Chemistry, Medicinal
Jed F. F. Fisher, Shahriar Mobashery
Summary: This essay discusses the discovery of beta-lactam antibiotics and their transformation of modern medicine, while also pointing out the scarcity of beta-lactam compounds in marine organisms and their potential similarity to quorum sensing molecules. The author proposes the exploration of this similarity to discover new structures and enzyme targets for interesting biological activities.
Article
Biochemistry & Molecular Biology
Luis F. Avila-Cobian, Hidekazu Hoshino, Mark E. Horsman, Van T. Nguyen, Yuanyuan Qian, Rhona Feltzer, Choon Kim, Daniel D. Hu, Matthew M. Champion, Jed F. Fisher, Shahriar Mobashery
Summary: This study reveals the localization and interactome of RlpA enzyme in Pseudomonas aeruginosa during cell division. Through the incorporation of non-canonical amino acids and photoaffinity capture, it is confirmed that RlpA enzyme mainly exists in the bacterial divisome. These methods provide new means for the localization study of bacterial proteins.
Article
Chemistry, Multidisciplinary
Mijoon Lee, Dusan Hesek, Jaroslav Zajicek, Jed F. Fisher, Shahriar Mobashery
CHEMICAL COMMUNICATIONS
(2017)