Review
Microbiology
Manon Lang, Andre Carvalho, Zeynep Baharoglu, Didier Mazel
Summary: This review aims to consolidate existing and recent knowledge about the uptake of aminoglycosides (AGs), explore the connection between AG-dependent bacterial stress and drug uptake, and present new strategies to enhance AG uptake for more efficient antibiotic therapies, with a focus on the connection between sugar transport and AG potentiation.
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS
(2023)
Article
Multidisciplinary Sciences
Kumar Sachin Singh, Rishabh Sharma, Poli Adi Narayana Reddy, Prashanthi Vonteddu, Madeline Good, Anjana Sundarrajan, Hyeree Choi, Kar Muthumani, Andrew Kossenkov, Aaron R. Goldman, Hsin-Yao Tang, Maxim Totrov, Joel Cassel, Maureen E. Murphy, Rajasekharan Somasundaram, Meenhard Herlyn, Joseph M. Salvino, Farokh Dotiwala
Summary: Isoprenoids are essential for maintaining cellular functions and IspH is a crucial enzyme in their synthesis pathway. Through structure-guided design, a class of IspH inhibitors with nanomolar potency were identified, showing efficacy against multidrug-resistant bacteria while being relatively non-toxic to mammalian cells. These prodrugs also induce expansion and activation of human V gamma 9V delta 2 T cells, suggesting a potential strategy to limit antibiotic-resistant bacterial populations.
Review
Microbiology
Claire Maher, Karl A. Hassan
Summary: Gram-negative bacteria are resistant to antibiotics due to their cell envelope's permeability barrier. Understanding the role of different components in the envelope is crucial for developing new broad-spectrum antibiotics.
Article
Infectious Diseases
Antonella Migliaccio, Maria Stabile, Maria Bagattini, Maria Triassi, Rita Berisio, Eliana De Gregorio, Raffaele Zarrilli
Summary: Resveratrol can reverse tolerance and restore susceptibility to CHX and BZK in the majority of microorganisms causing HAI. The efflux pump inhibitor reduced the MIC and MBC of CHX and BZK in most strains, while resveratrol dose-dependently decreased the MIC and MBC of the biocides.
Review
Immunology
Jing Zhang, Ling Chen, Yang Yang, Xiao Liu, Yuan Yuan, Shi-rong Song, Yue Zhao, Jian Mao
Summary: The purpose of this study was to compare the clinical and laboratory characteristics of late-onset sepsis (LOS) caused by Gram-negative and Gram-positive bacteria in preterm neonates and evaluate the diagnostic accuracy of biomarkers. The results showed that LOS caused by Gram-negative bacteria in preterm neonates had higher levels of CRP and lower platelet counts. Therefore, platelet count and CRP values may be useful biomarkers to differentiate sepsis caused by Gram-negative and Gram-positive bacteria in preterm neonates.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Infectious Diseases
Laurent Dortet, Claudia Niccolai, Niels Pfennigwerth, Stefanie Frisch, Camille Gonzalez, Alberto Antonelli, Tommaso Giani, Robert Hoenings, Soeren Gatermann, Gian Maria Rossolini, Thierry Naas
Summary: In this study, the clinical performance of Bruker's UMIC (R) Cefiderocol method for determining the minimum inhibitory concentration (MIC) of Cefiderocol in clinically relevant bacteria was assessed. The results showed good agreement between the UMIC (R) Cefiderocol method and the reference method, indicating its suitability for determining Cefiderocol MIC values.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Chemistry, Medicinal
Azza Troudi, Jean Marie Pages, Jean Michel Brunelx
Summary: The outer membrane of Gram-negative bacteria serves as an efficient barrier against external harmful compounds and plays a crucial role in preventing the entry of antimicrobial agents. Current antibiotics mainly target intracellular components, requiring translocation across membranes. A better understanding of Lipid A synthesis and membrane assembly could lead to the development of new antibacterial drugs against microbial resistance.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Microbiology
Alicia Macias-Valcayo, John-Jairo Aguilera-Correa, Antonio Broncano, Raul Parron, Alvaro Aunon, Joaquin Garcia-Canete, Antonio Blanco, Jaime Esteban
Summary: This study analyzed a large number of isolates of Gram-negative bacilli that cause prosthetic joint infection. The study includes biofilm development and antimicrobial susceptibility testing of both planktonic and sessile bacteria. The results obtained support the clinical knowledge about the treatment of these bacteria when biofilms are involved.
MICROBIOLOGY SPECTRUM
(2022)
Review
Fisheries
Hien Van Doan, Mehdi Soltani, Einar Ringo
Summary: Gram-positive probiotic bacteria have been shown to be effective in preventing disease outbreaks in aquaculture by producing bioactive compounds that can inhibit potential pathogenic Gram-negative bacteria. They can also enhance host immune-physiological functions and improve disease resistance. Further research is needed to optimize probiotic dosages and understand the in vivo effects of Gram-positive probiotics.
Article
Multidisciplinary Sciences
Aliya Fazal, Sajida Ara, Muhammad Tayab Ishaq, Kalsoom Sughra
Summary: The study focuses on the green synthesis of copper oxide nanoparticles using vegetable peels, with an ecofriendly approach and low fabrication temperature. It also explores the antibacterial efficacy of the nanoparticles, showing a more significant biocidal effect on Gram-negative bacteria compared to Gram-positive bacteria. The research highlights the potential of utilizing biowaste for the production of useful products.
ARABIAN JOURNAL FOR SCIENCE AND ENGINEERING
(2022)
Review
Immunology
Jia Wang, Kun Xiong, Qu Pan, Weifeng He, Yanguang Cong
Summary: Bacteria require scarce nutrients like iron and nickel for growth, which are competitively absorbed from the environment by Gram-negative bacteria through the secretion of chelators. TonB-dependent transporters play a crucial role in mediating the transport of these nutrients into bacterial cells, making them excellent candidates for vaccine development. Researchers have recently explored the potential application of a large number of TBDTs in immune control of corresponding pathogens.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Guocheng Xie, Sijia Gao, Jinzhao Ou, Meng Zhu, Man Wu, Xiaoyan Ju, Zhuang Li, Ye Tian, Zhongwei Niu
Summary: By conjugating peptides onto tobacco mosaic virus, the resulting nanoparticles show significantly enhanced antibacterial effects against Gram-negative bacteria. The high osmotic pressure and reactive oxygen species generated by the peptide-TMV cause the death of Escherichia coli, while also downregulating biofilm-related genes to inhibit biofilm formation. This study opens up new possibilities for combating Gram-negative bacteria-related infections.
Article
Biotechnology & Applied Microbiology
Bing Wei, Yingmin Ma
Summary: The combination delivery of nanomedicine GF9 and streptomycin demonstrated a better effect on overall survival, anti-inflammatory, and anti-bacterial functions in sepsis.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Immunology
Wei-Feng Wang, Xiao-Yong Xie, Kang Chen, Xiu-Li Chen, Wei-Lin Zhu, Huan-Ling Wang
Summary: The Chinese horseshoe crab relies on its innate immune system for pathogen defense, but the specific mechanisms underlying its abilities to distinguish and defend against invading microbes are still unclear. Through high-throughput sequencing and bioinformatics analysis, this study identified key signaling pathways activated in the Chinese horseshoe crab's hemolymph in response to Gram-negative bacteria, shedding light on the ancient original innate immune mechanism.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Frank Mickoleit, Cornelia Joerke, Stefan Geimer, Denis S. Maier, Jorg P. Muller, Johanna Demut, Christine Graefe, Dirk Schuler, Joachim H. Clement
Summary: Magnetosomes are biogenic, magnetic nanoparticles synthesized by magnetotactic bacteria, showing high crystallinity, strong magnetization, and uniform shape and size, making them promising alternatives for various applications in biotechnology and biomedicine. Studies have demonstrated concentration-dependent biocompatibility of isolated magnetosomes for different cell lines, affecting cell proliferation but not viability, with strong magnetosome-cell interactions allowing for magnetic cell sorting.
NANOSCALE ADVANCES
(2021)
Article
Chemistry, Multidisciplinary
Claire Cheyenne Jimidar, Joerg Grunenberg, Bianka Karge, Hazel Leanne Sarah Fuchs, Mark Broenstrup, Philipp Klahn
Summary: This article discusses the development of a novel amino trimethyl lock system for the release of fluorophores, which was successfully applied for imaging H2S in human cells in vitro.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Virology
Henrike P. Ahsendorf, Ulrike S. Diesterbeck, Sven-Kevin Hotop, Michael Winkler, Mark Broenstrup, Claus-Peter Czerny
Summary: A human single-chain fragment variable (scFv) library was constructed and an anti-F13 scFv was isolated and characterized. The antigenic binding sites of the scFv were determined. The study suggests that constructing recombinant immunoglobulin libraries is a promising strategy for studying host-pathogen interactions.
Article
Chemistry, Multidisciplinary
Carsten Peukert, Sachin Popat Gholap, Ori Green, Lukas Pinkert, Joop van den Heuvel, Marco van Ham, Doron Shabat, Mark Broenstrup
Summary: Conjugating siderophore moieties with enzyme-activatable dioxetanes resulted in trifunctional probes with high signal-to-background ratios, allowing for sensitive and selective detection of bacteria. The efficient iron transport capability into bacteria was confirmed through a growth recovery assay, highlighting the potential applications of these probes in bacterial detection.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Microbiology
Sebastian Suerbaum, Nina Coombs, Lubna Patel, Dimitri Pscheniza, Katharina Rox, Christine Falk, Achim D. Gruber, Olivia Kershaw, Patrick Chhatwal, Mark Broenstrup, Ursula Bilitewski, Christine Josenhans
Summary: This study developed a novel screening system for inhibitors of H. pylori motility and flagellar assembly, and identified numerous novel antibacterial and anti-motility compounds (antimotilins). One of the antimotilin compounds showed good efficacy in reducing bacterial colonization in a mouse model, indicating its potential as a therapy against H. pylori infection.
Article
Chemistry, Medicinal
Sarah Fritsch, Veronique Gasser, Carsten Peukert, Lukas Pinkert, Lauriane Kuhn, Quentin Perraud, Vincent Normant, Mark Broenstrup, Isabelle J. Schalk
Summary: This study demonstrates that synthetic siderophore mimetics MECAM and DOTAM can transport iron into Pseudomonas aeruginosa cells via specific outer membrane transporters. MECAM induces the expression of pfeA gene, while the conjugate 3 increases the expression of both pfeA and ampc genes. DOTAM does not induce the expression of pirA gene but upregulates the expression of zinc transporters cntO and PA0781. Iron uptake experiments show that MECAM and DOTAM are as efficient as the natural siderophore enterobactin.
ACS INFECTIOUS DISEASES
(2022)
Article
Chemistry, Medicinal
Carsten Peukert, Veronique Gasser, Till Orth, Sarah Fritsch, Vincent Normant, Olivier Cunrath, Isabelle J. Schalk, Mark Broenstrup
Summary: This study identifies the inner membrane protein TonB as a novel target in antimicrobial therapy and demonstrates a cellular suicide mechanism where a transporter imports its own inhibitor. Three conjugates of TonB box peptides and synthetic siderophores inhibit the growth of Pseudomonas aeruginosa cells without producing their own siderophores. The transporters responsible for the uptake of these compounds were identified as PfeA and PirA.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Carsten Peukert, Katharina Rox, Bianka Karge, Sven-Kevin Hotop, Mark Broenstrup
Summary: The rise of antimicrobial resistance, especially in Gram-negative bacteria, requires new diagnostics and antibiotics. Researchers conjugated potent antibiotics with catechol siderophores to enhance their uptake into bacteria. However, the transfer to the cytosol was insufficient, limiting the antibiotic efficacy.
ACS INFECTIOUS DISEASES
(2023)
Article
Chemistry, Medicinal
Yi-Hui Lai, Raimo Franke, Lukas Pinkert, Heike Overwin, Mark Broenstrup
Summary: A study found that a siderophore-antibiotic conjugate, which targets the bacterial iron transport system, can effectively inhibit E. coli but also leads to regrowth at high concentrations, known as the "Eagle effect." Transcriptome and untargeted metabolome analysis revealed that the Eagle effect not only causes paradoxical growth but also induces unique gene expression and metabolite profiles.
ACS INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Yingwen Wu, Ben G. E. Zoller, Mohamed Ashraf Mostafa Kamal, Sven-Kevin Hotop, Claus-Michael Lehr, Mark Broenstrup, Petra Dersch, Martin Empting
Summary: Polymicrobial infections can cause acute and chronic diseases in the gastrointestinal and respiratory tracts. This study aims to modulate microbial communities by targeting the posttranscriptional regulator system called carbon storage regulator A (CsrA). A luciferase reporter gene assay combined with a qPCR expression gene assay has been successfully developed to evaluate the cellular effects of CsrA-regulated mechanisms. The assay enables the monitoring of downstream targets of CsrA and the evaluation of non-bactericidal/non-bacteriostatic compounds targeting CsrA/RsmA.
Article
Chemistry, Medicinal
Lunan Jian, Robert Zscherp, Ulrike Beutling, Xiaofei Shen, Shiyang Xu, Xia Zhang, Mark Broenstrup, Philipp Klahn, Qingxiang Sun
Summary: In this study, four aminoratjadone derivatives were synthesized and two of them, KL1 and KL2, were found to be noncovalent CRM1 inhibitors. The compounds underwent spontaneous hydrolysis in aqueous buffers and the resulting products showed higher activity against CRM1. High-resolution crystal structures revealed the binding mode of these compounds to CRM1 and explained the structure-activity relationships. In cells, KL1 and KL2 localized CRM1 in the nuclear periphery and led to depletion of nuclear CRM1, thereby inhibiting the nuclear export and growth of colorectal cancer cells at submicromolar concentrations. This work lays the foundation for further development of aminoratjadone-based noncovalent CRM1 inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Microbiology
Esteban Charria-Giron, Yasmina Marin-Felix, Ulrike Beutling, Raimo Franke, Mark Broenstrup, Aida M. Vasco-Palacios, Nelson H. Caicedo, Frank Surup
Summary: This study systematically investigated the secondary metabolite production of a previously undescribed species of Diaporthe from medicinal plants and discovered several compounds, confirming phomol as the main antimicrobial component. Additionally, novel butenolides unrelated to phomol were identified. The study emphasizes the importance of correct interpretation of untargeted metabolomics approaches and encourages further exploration of endophytic fungi from traditional medicinal plants for the discovery of new natural products.
MICROBIOLOGY SPECTRUM
(2023)
Article
Chemistry, Multidisciplinary
Julia Friederich, Chunfa Xu, Patrick Raunft, Hazel L. S. Fuchs, Mark Broenstrup
Summary: We describe a chemically triggered click-to-release system that combines the trimethyl lock (TML) lactonization with the bioorthogonal inverse electron demand Diels-Alder (IEDDA) reaction of a vinyl ether and a tetrazine. The IEDDA reaction was found to be rate-limiting in the three-step sequence. The reaction rates could be enhanced by increasing the electrophilicity of the tetrazine, while maintaining reactivity and stability. The system was successfully demonstrated with the release of an anticancer drug from a vinyl-modified TML.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Carsten Peukert, Anna C. Vetter, Hazel L. S. Fuchs, Kirsten Harmrolfs, Bianka Karge, Marc Stadler, Mark Bronstrup
Summary: The study aimed to enhance the potency of existing antibiotics against antibiotic-resistant Gram-negative bacteria. By utilizing the microbial iron transport machinery, covalent modifications were made to improve drug translocation across the cell membrane. Cleavable linkers were designed to release the antibiotic inside the bacteria and unperturbed target binding. The conjugates showed increased antibiotic activity against multidrug-resistant E. coli compared to free rifamycin, suggesting the potential of this approach to boost the effectiveness of existing antibiotics.
Article
Chemistry, Multidisciplinary
Jan W. Schwitalla, Ngoc-Thao-Hien Le, Soohyun Um, Felix Schalk, Mark Bronstrup, Martin Baunach, Christine Beemelmanns
Summary: After analyzing the cryptic mdk cluster region and performing transcriptomic studies, a Streptomyces BAC vector containing the mdk gene sequence was constructed and used for heterologous expression in different Streptomyces strains. The expressed mdk cluster produced a novel compound called seongomycin, which exhibited antibacterial, antiproliferative, and antiviral activities. The core structure of maduralactomycin A was also revised using a computational approach.
Article
Chemistry, Medicinal
Mark S. Cooper, Linlin Zhang, Mohamed Ibrahim, Kaixuan Zhang, Xinyuanyuan Sun, Judith Roeske, Matthias Goehl, Mark Broenstrup, Justin K. Cowell, Lucie Sauerhering, Stephan Becker, Laura Vangeel, Dirk Jochmans, Johan Neyts, Katharina Rox, Graham P. Marsh, Hannah J. Maple, Rolf Hilgenfeld
Summary: This article discusses the potential application of inhibitors targeting the main protease (Mpro) of SARS-CoV-2 in COVID-19 treatment. The study found that 13b-K is an effective inhibitor and shows promise for further development as an antiviral treatment for COVID-19.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)