Article
Biochemistry & Molecular Biology
Matthew Thomas Doyle, Harris David Bernstein
Summary: The study found that the beta-barrel assembly machine (BAM) subunit BamA not only catalyzes the integration of beta-barrel proteins, but also functions as a polypeptide export channel, facilitating the traversal of virulence factor structures through its beta-barrel lumen. This discovery establishes a new function for BamA and unifies the divergent functions of BamA and other Omp85 superfamily transporters.
Article
Biochemistry & Molecular Biology
Shashanka Aroli, Eui-Jeon Woo, Balasubramanian Gopal, Umesh Varshney
Summary: UdgX removes uracil from uracil-containing DNA and forms a covalent bond with the resulting AP-DNA. It is structurally similar to family-4 UDGs (F4-UDGs) but unique in possessing a flexible R-loop (105KRRIH109). Mutations in UdgX reveal the role of specific amino acids in its enzymatic activity and substrate binding.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Christopher Ruis, Aaron Weimann, Gerry Tonkin-Hill, Arun Prasad Pandurangan, Marta Matuszewska, Gemma G. R. Murray, Roger C. Levesque, Tom L. Blundell, R. Andres Floto, Julian Parkhill
Summary: The study reveals that mutagens and defects in DNA repair can generate context-specific mutational signatures in bacteria, similar to the findings in cancer cells. By reconstructing mutational spectra and analyzing bacterial lineages, the researchers identified mutational patterns associated with DNA repair defects and niche-specific mutagens. These mutational signatures were found to be influenced by both bacterial phylogeny and replication niche. The results suggest that mutational spectra can be used to infer transmission routes for bacterial pathogens.
NATURE COMMUNICATIONS
(2023)
Article
Infectious Diseases
Shazad Mushtaq, Anna Vickers, Nicholas Ellaby, Neil Woodford, David M. Livermore
Summary: The study found that the risk of mutational resistance to aztreonam/avibactam appears smaller than for ceftazidime/avibactam. Asn346 substitutions in AmpC enzymes may remain a risk for resistance.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Chemistry, Multidisciplinary
Charles Burridge, Christopher A. Waudby, Tomasz Wlodarski, Anais M. E. Cassaignau, Lisa D. Cabrita, John Christodoulou
Summary: This study used solution-state NMR spectroscopy to measure transverse proton relaxation rates for methyl groups in folded ribosome-nascent chain complexes, revealing interactions between the nascent chain and ribosome surface driven predominantly by electrostatics. By observing changes in these interactions as subsequent domain emerges, the impact on free energy landscapes associated with co-translational folding process can be deduced.
Article
Multidisciplinary Sciences
Alaksh Choudhury, Benoit Gachet, Zoya Dixit, Roland Faure, Ryan T. Gill, Olivier Tenaillon
Summary: Mutations in RNA polymerase can promote growth or maintenance by altering molecular functions, and these mutations can cluster in two modules. Combining mutations from both modules enhances adaptive evolution.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Shogo Ozaki, Dengyu Wang, Yasutaka Wakasugi, Naoto Itani, Tsutomu Katayama
Summary: In this study, the researchers demonstrated the important role of DciA in maintaining DNA replication forks using the model bacterium Caulobacter crescentus. They found that DciA promotes loading of DnaB onto single-stranded DNA through conformational changes in the DnaB hexamer, ensuring proper progression of the replication fork.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Philipp Wendering, Marius Arend, Zahra Razaghi-Moghadam, Zoran Nikoloski
Summary: Turnover numbers of enzymes are a key property that can improve the prediction accuracy of cellular phenotypes in metabolic modeling. However, in vitro and in vivo turnover numbers alone do not lead to accurate predictions of condition-specific growth rates of E. coli and S. cerevisiae, especially when considering protein abundances. By correcting turnover numbers using proteomics and physiological data, we demonstrate improved predictions of condition-specific growth rates. Our approach provides a means to correct turnover numbers and catalog kcatomes of other organisms.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Marc A. Beal, Matthew J. Meier, Angela Dykes, Carole L. Yauk, Iain B. Lambert, Francesco Marchetti
Summary: This study provides a comprehensive and detailed map of amino acid residues affecting the structure and catalytic activity of the beta-gal enzyme, based on the analysis of lacZ mutations.
Article
Multidisciplinary Sciences
Francois Bertaux, Sebastian Sosa-Carrillo, Viktoriia Gross, Achille Fraisse, Chetan Aditya, Mariela Furstenheim, Gregory Batt
Summary: Small-scale, low-cost bioreactors are gaining popularity in quantitative systems and synthetic biology. In this study, the authors present ReacSight, a strategy that enhances bioreactor arrays by connecting them with sensitive measurement devices using low-cost pipetting robots. They demonstrate the capabilities of ReacSight in yeast, including real-time optogenetic control of gene expression, exploration of nutrient scarcity effects on fitness and cellular stress, and dynamic control of a two-strain consortium's composition.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Axel von Kamp, Steffen Klamt
Summary: In this study, a method is presented to modify the stoichiometry of the biomass reaction in order to make the flux balance analysis problem feasible and improve the accuracy of the model. Realistic flux measurements of E.coli are used to demonstrate the value of this approach, highlighting the overestimation of growth-associated maintenance (GAM) demand of ATP in recent genome-scale models.
Article
Multidisciplinary Sciences
Helena Massana-Cid, Claudio Maggi, Giacomo Frangipane, Roberto Di Leonardo
Summary: Optical feedback can be used to confine and gather bacteria, forming dense high-activity regions. This method is general and scalable, making it versatile for microengineering applications and studying non-equilibrium phenomena in active systems.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Camille Mumm, Melissa L. Drexel, Torrin L. McDonald, Adam G. Diehl, Jessica A. Switzenberg, Alan P. Boyle
Summary: Recombinant plasmid vectors are versatile tools that have facilitated discoveries in various fields. However, errors can be introduced during the process of creating recombinant DNA, making sequence validation essential. While Sanger sequencing is the current standard for plasmid validation, it has limitations in sequencing complex secondary structures and scaling for full-plasmid sequencing. This article introduces OnRamp, an alternative method that combines the advantages of high-throughput sequencing and Sanger sequencing by leveraging nanopore's long-read sequencing technology. It provides customized wet-lab protocols and an analysis pipeline for plasmid preparation and data processing, aiming to make long-read sequencing more accessible for routine plasmid validation.
Article
Biochemistry & Molecular Biology
Chantal K. Guegler, Michael T. Laub
Summary: Research has found that toxin-antitoxin system toxIN can protect E. coli against bacteriophages, with ToxN being activated following T4 infection to inhibit phage development by cleaving viral mRNAs. Transcriptional shutoff is crucial for ToxN activation, but toxIN does not provide strong protection against T7 phage, indicating a critical trade-off in blocking host transcription.
Article
Infectious Diseases
Meng-Ke Zhang, Meng-Yao Zhang, Shuo-Bo Liu, Ying-Ying Yang, Ya-Jun Zhai, Dan-Dan He, Hua Wu, Yu-Shan Pan, Jian-Hua Liu, Li Yuan, Gong-Zheng Hu
Summary: This study revealed that the double deletion of cpxR and tolC significantly increases the susceptibility of S. Typhimurium to colistin. The molecular mechanisms underlying this phenomenon were elucidated through transcriptomic analysis.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Microbiology
Anja Pavlin, Gregor Bajc, Nadine Fornelos, Douglas F. Browning, Matej Butala
Summary: We previously identified a 50-residue bacteriophage protein, gp7, which interacts with and modulates the function of the LexA transcription factor from Bacillus thuringiensis. Our data indicates that the small DdrR protein from A. baumannii likely coordinates the SOS response and prophage processes by also interacting with LexA superfamily members. The discovery of DdrR's role in DNA damage response and prophage induction in A. baumannii could have significant implications for understanding and combating the threat posed by this bacterium in healthcare settings.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Joanne Hothersall, Sandie Lai, Nan Zhang, Rita E. Godfrey, Patcharawarin Ruanto, Sarah Bischoff, Colin Robinson, Tim W. Overton, Stephen J. W. Busby, Douglas F. Browning
Summary: This article describes a vector system controlled by the nitrate-responsive transcription activator protein in Escherichia coli for high-level controlled recombinant protein production. The use of nitrate allows for a simplified and cost-effective approach, as it is a cheap and abundant inorganic ion. The study demonstrates the expression of target proteins to high levels using this system and shows that inexpensive garden products can be used for controlled protein production due to the high nitrate levels present in commercial fertilizers.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Article
Marine & Freshwater Biology
Margot K. Vermeylen, Toby G. Knowles, Heather W. Barron
Summary: The study reveals an increasing trend of Karenia brevis red tides along Florida's coast, potentially caused by anthropogenic eutrophication, which results in an increased number of affected wildlife. Moreover, water discharges from the Okeechobee waterway are significantly correlated with K. brevis densities. Different species groups exhibit significant correlations with K. brevis cell counts, particularly the double-crested cormorants.
Article
Microbiology
Gabriela Boelter, Jack A. Bryant, Hannah Doherty, Peter Wotherspoon, Dema Alodaini, Xuyu Ma, Micheal B. Alao, Patrick J. Moynihan, Danesh Moradigaravand, Monika Glinkowska, Timothy J. Knowles, Ian R. Henderson, Manuel Banzhaf
Summary: Bacterial amidases are important for cell separation, and their activity needs to be precisely controlled. Recent studies suggested that the outer membrane lipoprotein DolP could be a regulator of amidases, but this study showed that DolP does not directly regulate amidase function. However, DolP may impact cell separation through other mechanisms.
Article
Multidisciplinary Sciences
Gideon Mamou, Federico Corona, Ruth Cohen-Khait, Nicholas G. Housden, Vivian Yeung, Dawei Sun, Pooja Sridhar, Manuel Pazos, Timothy J. Knowles, Colin Kleanthous, Waldemar Vollmer
Summary: The spatiotemporal organization of outer membrane proteins (OMPs) in Gram-negative bacteria is modulated by the presence of mature peptidoglycan, which inhibits OMP foldase activity and promotes preferential insertion of OMPs at division sites. This coordination between OMP biogenesis and peptidoglycan maturation represents a potential vulnerability that could be targeted in future antibiotic design.
Article
Multidisciplinary Sciences
Michael Overduin, Troy A. Kervin, Anh Tran
Summary: Membrane recognition by viral spike proteins plays a critical role in virus infection. This study investigates the binding of different spike protein variants, including those from SARS-CoV-2 and related viruses, to host cell membranes. The results show that these variants exhibit increased membrane binding tendencies over time, with mutations in the spike head region, particularly in variant BA.1, affecting the affinity to cell membranes. Comparison of multiple structures reveals a progressive model of membrane docking, where spike protein trimers transition from perpendicular to tilted positions, facilitating viral particle adhesion to host cell membranes and potential engagement with ACE2 receptors. Enhanced membrane interactions in variants explain their unique cell fusion capacities and the transmission of COVID-19.
Review
Agriculture, Dairy & Animal Science
K. A. Fletcher, G. Limon, L. J. Whatford, A. Grist, T. G. Knowles, T. J. Gibson
Summary: This systematic review found a lack of consistent guidance on equine slaughter globally, along with a shortage of research on equine welfare during the slaughter process, particularly concerning donkeys and mules in low-income countries. The need to urgently develop an evidence base to improve guidance in this area was highlighted.
Article
Biology
Maryam Jama, Marawan Ahmed, Anna Jutla, Carson Wiethan, Jitendra Kumar, Tae Chul Moon, Frederick West, Michael Overduin, Khaled H. Barakat
Summary: This study utilized computational tools to screen over 6 million compounds and identified three potent allosteric inhibitors of SHP2. The binding affinities of these inhibitors to SHP2 were measured and found to be in the nanomolar range, suggesting their potential as improved allosteric inhibitors of SHP2.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Virology
Michael Overduin, Rakesh K. K. Bhat, Troy A. A. Kervin
Summary: Variants of the Omicron subvariants of SARS-CoV-2 exhibit strong membrane binding abilities and can evade antibodies from vaccinations and previous infections. Despite differences around mutated sites, they all maintain elevated membrane binding propensities and exhibit both closed and open states. These findings provide predictive criteria for future pandemic waves and strategies for combating multiple variants.
Article
Immunology
Maryam Shojaei, Amir Shamshirian, James Monkman, Laura Grice, Minh Tran, Chin Wee Tan, Siok Min Teo, Gustavo Rodrigues Rossi, Timothy R. McCulloch, Marek Nalos, Maedeh Raei, Alireza Razavi, Roya Ghasemian, Mobina Gheibi, Fatemeh Roozbeh, Peter D. Sly, Kirsten M. Spann, Keng Yih Chew, Yanshan Zhu, Yao Xia, Timothy J. Wells, Alexandra Cristina Senegaglia, Carmen Lucia Kuniyoshi, Claudio Luciano Franck, Anna Flavia Ribeiro dos Santos, Lucia de Noronha, Sepideh Motamen, Reza Valadan, Omolbanin Amjadi, Rajan Gogna, Esha Madan, Reza Alizadeh-Navaei, Liliana Lamperti, Felipe Zuniga, Estefania Nova-Lamperti, Gonzalo Labarca, Ben Knippenberg, Velma Herwanto, Ya Wang, Amy Phu, Tracy Chew, Timothy Kwan, Karan Kim, Sally Teoh, Tiana M. Pelaia, Win Sen Kuan, Yvette Jee, Jon Iredell, Ken O'Byrne, John F. Fraser, Melissa J. Davis, Gabrielle T. Belz, Majid E. Warkiani, Carlos Salomon Gallo, Fernando Souza-Fonseca-Guimaraes, Quan Nguyen, Anthony Mclean, Arutha Kulasinghe, Kirsty R. Short, Benjamin Tang
Summary: This study found that the IFI27 gene is associated with COVID-19 infection and that its expression levels in the respiratory tract and blood are correlated with viral load and infection severity. IFI27 gene family biomarkers may supplement conventional diagnostic tools in future virus pandemics.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Genetics & Heredity
Douglas F. Browning, Jon L. Hobman, Stephen J. W. Busby
Summary: Escherichia coli K-12, isolated 100 years ago, has become an invaluable model organism in molecular biology research. However, due to extensive laboratory manipulation, ancestral K-12 strains have undergone genetic changes. By sequencing the genomes of WG1 and EMG2 strains, considered to be the progenitors of many laboratory strains, it was found that they still carry genetic elements but have also undergone laboratory-based evolution. This raises the question of whether E. coli K-12 is a sufficiently robust model organism for 21st century microbiology.
MICROBIAL GENOMICS
(2023)
Review
Biotechnology & Applied Microbiology
Mark S. Butler, Ian R. Henderson, Robert J. Capon, Mark A. T. Blaskovich
Summary: The global need for new antibacterial drugs to combat drug-resistant bacterial infections is receiving significant attention, leading to numerous funding, policy, and legislative initiatives to support antibacterial research and development. This review assesses the impact of these programs by analyzing the clinical development of various types of antibacterial drugs and the number of drug approvals in recent years. The findings show an increasing number of early-stage candidates and a presence of novel antibacterial compounds, particularly targeting Gram-negative bacteria.
JOURNAL OF ANTIBIOTICS
(2023)
Article
Chemistry, Multidisciplinary
James S. Craig, Larry Melidis, Hugo D. Williams, Samuel J. Dettmer, Alexandra A. Heidecker, Philipp J. Altmann, Shengyang Guan, Callum Campbell, Douglas F. Browning, Roland K. O. Sigel, Silke Johannsen, Ross T. Egan, Brech Aikman, Angela Casini, Alexander Pothig, Michael J. Hannon
Summary: Holliday 4-way junctions are important for DNA processes. Metallo-supramolecular pillarplexes can interact with open DNA junction cavities. They can bind 3-way junctions but disrupt base pairing, while they can bind and increase binding sites of 4-way junctions. This offers possibilities for biological and synthetic nucleic acid nanostructures.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Genetics & Heredity
Emily C. A. F. Goodall, Camila Azevedo A. Antunes, Jens Moeller, Vartul R. Sangal, Von Vergel L. Torres, Jessica Gray, Adam F. Cunningham, Paul A. Hoskisson, Andreas Burkovski, Ian R. Henderson
Summary: This study constructed the densest library of mutants for any Corynebacterium species and identified the essential genome of Corynebacterium diphtheriae. The identification of highly conserved genes and species-specific genes provides a basis for the future development of therapeutic options. Additionally, the study discovered uncharacterized proteins in the proteome that are also represented in the vaccine, which could be potential targets for antimicrobial and vaccine development.
Article
Biochemistry & Molecular Biology
Anh Tran, Troy A. Kervin, Michael Overduin
Summary: This study investigates the mechanism of interaction between the spike protein of SARS-CoV-2 and host cell membranes. Multiple binding sites between the spike protein and membranes are identified, which play a role in viral fusion, entry, assembly, and egress processes, as well as ACE2 receptor recognition. Antibodies targeting the spike protein block the membrane docking process that precedes ACE2 recognition.
CURRENT RESEARCH IN STRUCTURAL BIOLOGY
(2022)