Article
Multidisciplinary Sciences
Carmina Micelli, Yunfei Dai, Nicole Raustad, Ralph R. Isberg, Christopher G. Dowson, Adrian J. Lloyd, Edward Geisinger, Allister Crow, David I. Roper
Summary: Acinetobacter baumannii is a gram-negative bacterial pathogen that causes challenging nosocomial infections. The study reveals the molecular details of cell wall elongation inhibition upon zinc starvation in A. baumannii. The findings offer a perspective for dual inhibition of zinc-dependent peptidoglycan synthases and metallo-beta-lactamases by metal-chelating agents.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Microbiology
Shannon G. Murphy, Andrew N. Murtha, Ziyi Zhao, Laura Alvarez, Peter Diebold, Jung-Ho Shin, Michael S. VanNieuwenhze, Felipe Cava, Tobias Doerr
Summary: In Vibrio cholerae, endopeptidases are essential for proper cell elongation and division, while aPBPs become crucial for maintaining structural integrity during endopeptidase insufficiency, and the Rod system remains active but contributes minimally to cell expansion under these conditions.
Article
Infectious Diseases
Jinglan Wang, Laura Alvarez, Silvia Bulgheresi, Felipe Cava, Tanneke den Blaauwen
Summary: Peptidoglycan is crucial for bacterial survival and cell shape maintenance. Research on the gamma proteobacterium Candidatus Thiosymbion oneisti reveals its unique PG composition with high peptide cross-linkage and short glycan chains, as well as the involvement of endopeptidase PBP4 in septum formation. PBP4 shows different beta-lactam selectivity and potential allosteric binding site, suggesting a role in PG cleavage during longitudinal cell division and adaptation to a symbiotic lifestyle.
Article
Biochemistry & Molecular Biology
Jordan Delisle, Baptiste Cordier, Stephane Audebert, Matthieu Pophillat, Caroline Cluzel, Leon Espinosa, Christophe Grangeasse, Anne Galinier, Thierry Doan
Summary: Research indicates that TseB may be a novel regulator of PBPs, interacting with PBP2A to play a crucial role in cell wall elongation and spore germination.
MOLECULAR MICROBIOLOGY
(2021)
Article
Microbiology
Caroline Midonet, Sean Bisset, Irina Shlosman, Felipe Cava, David Z. Rudner, Thomas G. Bernhardt
Summary: The peptidoglycan layer protects bacteria and defines their shape. How class A penicillin-binding proteins (aPBPs) are controlled in Gram-positive bacteria is unclear. MacP, a regulator in Streptococcus pneumoniae, promotes PG polymerization by altering the TM-polymerase domain interface in PBP2a. Proper aPBP regulation is important for cell morphogenesis.
Article
Microbiology
Katarzyna Wacnik, Vincenzo A. Rao, Xinyue Chen, Lucia Lafage, Manuel Pazos, Simon Booth, Waldemar Vollmer, Jamie K. Hobbs, Richard J. Lewis, Simon J. Foster
Summary: Bacterial cell wall peptidoglycan synthesis is essential for bacterial growth and division and is targeted by clinically important antibiotics. Staphylococcus aureus, a human pathogen, has only two essential penicillin-binding proteins (PBPs) that are required for growth and division. Our recent studies have revealed a complex peptidoglycan architecture in S. aureus during division. PBP1 plays multiple essential roles in cell division, both as an enzyme and as a regulator.
Article
Microbiology
Katie N. Kang, Misha I. Kazi, Jacob Biboy, Joe Gray, Hannah Bovermann, Jessie Ausman, Cara C. Boutte, Waldemar Vollmer, Joseph M. Boll
Summary: The absence of PBP1A results in septation defects and cell chaining in Acinetobacter baumannii, supporting the isolation of colistin-resistant LOS- strains. Only isolates producing multiple septa are able to develop resistance. Defects in PBP1A glycosyltransferase activity and LD-transpeptidase activity play a role in remodeling the cell envelope to support colistin-resistant LOS- A. baumannii.
Article
Multidisciplinary Sciences
Brooke M. Britton, Remy A. Yovanno, Sara F. Costa, Joshua McCausland, Albert Y. Lau, Jie Xiao, Zach Hensel
Summary: In this study, the structure and dynamics of the E. coli divisome core complex were investigated using various techniques including structure prediction, molecular dynamics simulation, single-molecule imaging, and mutagenesis. The interactions and roles of proteins FtsW, FtsI, FtsQ, FtsL, FtsB, and FtsN in the complex were explored. The findings provide insights into the mechanism of cell wall synthesis activation by FtsN through modulating interactions between FtsI and FtsW.
NATURE COMMUNICATIONS
(2023)
Article
Engineering, Environmental
Wonjae Kim, Minkyung Kim, Woojun Park
Summary: Lysine toxicity is observed in certain bacterial cells, but the molecular mechanisms behind this phenomenon are still unclear. Cyanobacteria like Microcystis aeruginosa cannot effectively transport and degrade lysine, resulting in its accumulation. The competitive uptake of lysine with arginine or ornithine and the substitution of lysine in the cell wall inhibit transpeptidation, causing irreversible damage to the photosynthetic system and membrane integrity, leading to the death of slow-growing cyanobacteria.
JOURNAL OF HAZARDOUS MATERIALS
(2023)
Article
Microbiology
Cassandra Lenoir, Anais Pelletier, Sylvie Manuse, Hugo Millat, Adrien Ducret, Anne Galinier, Thierry Doan, Christophe Grangeasse
Summary: This study characterizes the regulatory function of the previously unknown protein Spr1400 in controlling the activity and localization of two important Penicillin-binding proteins (PBPs), PBP1a and PBP2b, in Streptococcus pneumoniae. The research utilizes a combination of techniques including genetic manipulation, protein biochemistry, and microscopy imaging to demonstrate that Spr1400 interacts with PBPs and influences their dynamics during the cell cycle. These findings highlight the importance of Spr1400 as a spatio-temporal regulator of PBP1a and PBP2b in pneumococcal morphogenesis.
Review
Microbiology
Patricia D. A. Rohs, Thomas G. Bernhardt
Summary: The peptidoglycan cell wall plays a crucial role in bacterial growth and division, with its assembly and division mechanisms being key targets for antibiotic therapies. Understanding how the cell wall is built can lead to the development of new treatments for drug-resistant bacterial infections.
ANNUAL REVIEW OF MICROBIOLOGY, VOL 75, 2021
(2021)
Article
Plant Sciences
Ying Chang, Ning Tang, Min Zhang
Summary: This study provides molecular evidence for the link between chloroplast division and PG biosynthesis in P. patens, suggesting that PG biosynthesis is required for the constriction of the chloroplast division apparatus.
Review
Chemistry, Multidisciplinary
Sujeet Kumar, Aurelio Mollo, Daniel Kahne, Natividad Ruiz
Summary: This review summarizes recent major discoveries in peptidoglycan (PG) biogenesis, with a focus on the translocation of Lipid II and the SEDs glycosyltransferases. These findings may lead to the development of new antibiotics to combat bacterial resistance.
Article
Biology
Victor M. Hernandez-Rocamora, Natalia Baranova, Katharina Peters, Eefjan Breukink, Martin Loose, Waldemar Vollmer
Summary: Peptidoglycan is a crucial part of the bacterial cell envelope, and the Class A penicillin-binding proteins are essential enzymes involved in its synthesis. Researchers have developed a new assay to study the mechanisms of these enzymes in a lipid-bilayer environment, opening up possibilities for new directions in peptidoglycan synthesis research.
Article
Multidisciplinary Sciences
Marios F. Sardis, Jessica L. Bohrhunter, Neil G. Greene, Thomas G. Bernhardt
Summary: Bacterial cells are surrounded by cell walls made of the heteropolymer peptidoglycan (PG), with penicillin-binding proteins (aPBPs) playing key roles in building the PG network. Research has shown that the lipoprotein LpoA has a significant impact on the activity of PBP1a in cells and is crucial for glycan synthesis activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Manuel Banzhaf, Hamish C. L. Yau, Jolanda Verheul, Adam Lodge, George Kritikos, Andre Mateus, Baptiste Cordier, Ann Kristin Hov, Frank Stein, Morgane Wartel, Manuel Pazos, Alexandra S. Solovyova, Eefjan Breukink, Sven van Teeffelen, Mikhail M. Savitski, Tanneke den Blaauwen, Athanasios Typas, Waldemar Vollmer
Article
Chemistry, Multidisciplinary
Matej Sova, Rok Frlan, Stanislav Gobec, Zdenko Casar
Article
Chemistry, Medicinal
Ursa Pecar Fonovic, Damijan Knez, Martina Hrast, Nace Zidar, Matic Proj, Stanislav Gobec, Janko Kos
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Kaja Rozman, Evan M. Alexander, Eva Ogorevc, Kristof Bozovicar, Izidor Sosic, Courtney C. Aldrich, Stanislav Gobec
Article
Chemistry, Medicinal
Tim Van de Walle, Marina Briand, Ana Mitrovic, Izidor Sosic, Stanislav Gobec, Janko Kos, Leentje Persoons, Dirk Daelemans, Steven De Jonghe, Zorica Ubiparip, Tom Desmet, Kristof Van Hecke, Sven Mangelinckx, Matthias D'hooghe
Article
Biology
Victor M. Hernandez-Rocamora, Natalia Baranova, Katharina Peters, Eefjan Breukink, Martin Loose, Waldemar Vollmer
Summary: Peptidoglycan is a crucial part of the bacterial cell envelope, and the Class A penicillin-binding proteins are essential enzymes involved in its synthesis. Researchers have developed a new assay to study the mechanisms of these enzymes in a lipid-bilayer environment, opening up possibilities for new directions in peptidoglycan synthesis research.
Article
Biochemistry & Molecular Biology
Martin van Eijk, Albert van Dijk, Cornelis K. van Der Ent, Hubertus G. M. Arets, Eefjan Breukink, Nico van Os, Roy Adrichem, Sven van Der Water, Rita Lino Gomez, Maartje Kristensen, Martin Hessing, Shehrazade Jekhmane, Markus Weingarth, Ruud A. W. Veldhuizen, Edwin J. A. Veldhuizen, Henk P. Haagsman
Summary: PepBiotics, a novel class of antimicrobial peptides, showed promising antibacterial properties against CF-related respiratory pathogens, with CR-163 demonstrating the most potential for treatment. These observations highlight the therapeutic potential of PepBiotics against CF-related bacterial respiratory infections.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Article
Biochemistry & Molecular Biology
Tjasa Mazej, Damijan Knez, Anze Meden, Stanislav Gobec, Matej Sova
Summary: The study successfully synthesized three dual-acting compounds inhibiting two enzymes related to the pathobiology of Alzheimer's disease by introducing a carbamate moiety on the structure of an in-house irreversible monoamine oxidase B (MAO-B) inhibitor, with compound 15 demonstrating the best balanced inhibition effect.
Article
Microbiology
Xinghong Zhao, Xiaoqi Wang, Rhythm Shukla, Raj Kumar, Markus Weingarth, Eefjan Breukink, Oscar P. Kuipers
Summary: The study identified and characterized a novel antimicrobial candidate, brevibacillin 2V, from Brevibacillus laterosporus DSM 25, which exhibited strong antimicrobial activity against Gram-positive bacterial pathogens and low cytotoxicity to eukaryotic cells compared to other NRPs of the same family. Brevibacillin 2V showed good stability in human plasma and has the potential to be developed as a promising antibiotic with low hemolytic activity and cytotoxicity.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Microbiology
Xinghong Zhao, Xiaoqi Wang, Rhythm Shukla, Raj Kumar, Markus Weingarth, Eefjan Breukink, Oscar P. Kuipers
Summary: Lipo-tridecapeptides are effective against Gram-positive pathogens, but often exhibit high hemolytic activity and cytotoxicity, limiting their potential as antibiotics. However, a novel lipo-tridecapeptide, brevibacillin 2V, shows low hemolytic activity and cytotoxicity, and acts as a bactericidal agent against MRSA by binding to and permeabilizing the bacterial membrane. This study provides insight into the antimicrobial mode of action of brevibacillin 2V, aiding in its development as an alternative antimicrobial agent.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Katarina Grabrijan, Nika Strasek, Stanislav Gobec
Summary: Monocyclic ss-lactams have a wide range of biological activities, including antibacterial, anticancer, and cholesterol absorption inhibitory activities. This study presents an optimized synthesis method for orthogonally protected 3-amino-4-substituted monocyclic ss-lactams and investigates challenging deprotection methods. The results provide valuable insights into the synthesis and modification of monocyclic ss-lactams with potential pharmacological activities.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Bernarda Majc, Anamarija Habic, Metka Novak, Ana Rotter, Andrej Porcnik, Jernej Mlakar, Vera Zupunski, Ursa Pecar Fonovic, Damijan Knez, Nace Zidar, Stanislav Gobec, Janko Kos, Tamara Lah Turnsek, Anja Pislar, Barbara Breznik
Summary: This study found that cathepsin X is upregulated in human GBM tissues and localized in GBM cells, tumor-associated macrophages, and microglia. Selective cathepsin X inhibitors can decrease the viability of GBM cells and are colocalized with gamma-enolase, suggesting that cathepsin X is involved in GBM progression and could be a potential therapeutic target.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Ying Li, Adrien Boes, Yuanyuan Cui, Shan Zhao, Qingzhen Liao, Han Gong, Eefjan Breukink, Joe Lutkenhaus, Mohammed Terrak, Shishen Du
Summary: The study identified dominant-negative mutations in FtsW, a SEDS protein critical for septal PG synthesis, which likely constitute the active site of FtsW. These mutations block septal PG synthesis without affecting FtsW localization or activity.
Article
Cell Biology
Levente Kollar, Martina Gobec, Matic Proj, Lara Smrdel, Damijan Knez, Timea Imre, Agnes Gomory, Laszlo Petri, Peter Abranyi-Balogh, Dorottya Csanyi, Gyoergy G. Ferenczy, Stanislav Gobec, Izidor Sosic, Gyoergy M. Keseru
Summary: Constitutive- and immunoproteasomes are vital components of the protein homeostasis system. Selective inhibition of immunoproteasomes shows promise for treating various diseases, and two series of compounds targeting proteasomes have been described in this study. The compounds exhibit significant inhibitory activities against specific subunits of the proteasomes, highlighting their potential for developing selective immunoproteasome inhibitors or compounds targeting multiple subunits.
Article
Chemistry, Medicinal
Peter Abranyi-Balogh, Aaron Keeley, Gyorgy G. Ferenczy, Laszlo Petri, Timea Imre, Katarina Grabrijan, Martina Hrast, Damijan Knez, Janez Ilas, Stanislav Gobec, Gyorgy M. Keseru
Summary: The second generation of heterocyclic electrophiles, the quaternized analogue of the heterocyclic covalent fragment library, showed improved reactivity and MurA inhibitory potency. Quantum chemical reaction barrier calculations, GSH reactivity assay, and thrombin counter screen were used to explain the improved reactivity and selectivity of the N-methylated heterocycles and compare the two generations of heterocyclic electrophiles.
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)