Article
Chemistry, Medicinal
Damian L. Stachura, Stephanie Nguyen, Steven W. Polyak, Blagojce Jovcevski, John B. Bruning, Andrew D. Abell
Summary: In this study, the synthesis and assay of N1-diphenylmethyl triazole-based analogues were reported, which showed potent inhibitory activity against Staphylococcus aureus. The findings have important clinical implications for combating blood-based infections caused by Staphylococcus aureus.
ACS INFECTIOUS DISEASES
(2022)
Article
Chemistry, Medicinal
Damian L. Stachura, Stephanie Nguyen, Steven W. Polyak, Blagojce Jovcevski, John B. Bruning, Andrew D. Abell
Summary: The rise of multidrug-resistant bacteria has created an urgent need for new antibiotics, and one potential target is the enzyme biotin protein ligase (BPL). In this study, a new series of inhibitors of Staphylococcus aureus BPL (SaBPL) were designed, synthesized, and tested. Two particular compounds, triazoles 13 and 14, showed strong inhibition against SaBPL with Ki values of 10 +/- 2 and 30 +/- 6 nM, respectively, likely through hydrogen bonding interactions with amino acid residues S128 and N212 of SaBPL.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Review
Microbiology
Chaiyos Sirithanakorn, John E. Cronan
Summary: Biotin is a crucial enzyme cofactor required for metabolism in all domains of life, with bacterial biotin synthesis being a prime target for new therapeutic agents due to humans lacking a biotin synthetic pathway. The biotin synthetic pathway can be divided into early and late segments, and recent discoveries have shed light on new enzymes and pathways in different bacteria.
FEMS MICROBIOLOGY REVIEWS
(2021)
Article
Chemistry, Physical
Riya Samanta, Neel Sanghvi, Dorothy Beckett, Silvina Matysiak
Summary: Despite extensive research, the molecular basis of allostery remains unknown. This study compares allosteric and non-allosteric members of a protein family to uncover the distinguishing features that enable allostery in the Class II biotin protein ligases. Experimental, computational network, and bioinformatics analyses are used to reveal distinct residue community architectures, interactions, and coevolving residue networks in the two protein families, highlighting the importance of divergent local residue community network structures and inter-community interactions in enabling allostery.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Yevgeniy A. Gerassimovich, Samantha J. Miladinovski-Bangall, Kaitlin M. Bridges, Linkel Boateng, Lauren E. Ball, Homayoun Valafar, Anita Nag
Summary: The study identified multiple dynamic interactions of nsp1 with cellular proteins, including ribosomal proteins, pre-mRNA processing proteins, and stress granule-associated proteins. It was found that the interactions with transcription termination factors are primarily governed by the C-terminal region of nsp1.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Review
Cell Biology
Orhi Barroso-Gomila, Veronica Muratore, Laura Merino-Cacho, Jose Antonio Rodriguez, Rosa Barrio, James D. Sutherland
Summary: Post-translational modifications by ubiquitin and ubiquitin-like family members play a crucial role in regulating cellular protein homeostasis. The ubiquitin code encompasses the diverse family of modifications that lead to specific outcomes for substrates. Studying these modifications is challenging, but biotin-based methods facilitate the isolation and identification of substrates, modification sites, and the enzymes involved.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemical Research Methods
Shimon M. Rosenthal, Tvisha Misra, Hala Abdouni, Tess C. Branon, Alice Y. Ting, Ian C. Scott, Anne-Claude Gingras
Summary: Researchers adapted proximity labeling for protein discovery in zebrafish, developing in vivo TurbolD and mini-Turbo labeling techniques. By providing biotin directly in the egg water, they demonstrated successful biotinylation of prey proteins after 12 hours, enabling time-resolved analysis of development.
MOLECULAR & CELLULAR PROTEOMICS
(2021)
Article
Biochemistry & Molecular Biology
Liviu Cengher, Adhar C. Manna, Junho Cho, Jomkuan Theprungsirikul, Katherine Sessions, William Rigby, Ambrose L. Cheung
Summary: This study demonstrates that Teg49 in Staphylococcus aureus is an important regulatory sRNA that modulates resistance to myeloperoxidase-mediated killing by human neutrophils by regulating the expression of multiple genes distinct from sarA.
MOLECULAR MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xuejiao Song, Sarah K. Henke, John E. Cronan
Summary: This study investigates the functionality and mechanisms of action of two homologs of biotin protein ligase, BplA and BirA'. In vivo and in vitro assays show that BplA is functional, while BirA' acts as a biotin sensor involved in regulating biotin transport transcriptionally. Further evidence suggests an interaction between BplA and BirA' in vivo.
MOLECULAR MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Brianna K. Unda, Leon Chalil, Sehyoun Yoon, Savannah Kilpatrick, Courtney Irwin, Sansi Xing, Nadeem Murtaza, Anran Cheng, Chad Brown, Alexandria Afonso, Elizabeth McCready, Gabriel M. Ronen, Jennifer Howe, Aurelie Caye-Eude, Alain Verloes, Brad W. Doble, Laurence Faivre, Antonio Vitobello, Stephen W. Scherer, Yu Lu, Peter Penzes, Karun K. Singh
Summary: Copy number variations (CNVs) are associated with psychiatric and neurodevelopmental disorders (NDDs), and the underlying disease mechanisms for most CNVs are unknown. In this study, a 15q13.3 microdeletion mouse model and patient iPSC-derived neurons were used to investigate the developmental defects caused by the CNV. By targeting the 15q13.3 CNV genetic driver OTUD7A, the study revealed a critical OTUD7A-Ankyrin pathway in neuronal development and dysfunction in the 15q13.3 microdeletion syndrome.
MOLECULAR PSYCHIATRY
(2023)
Article
Infectious Diseases
Ying Jian, Tianming Li, Lin Zhao, Na Zhao, Yao Liu, Huiying Lv, Ya'nan Wang, Qian Liu, Min Li
Summary: Deletion in blaR1 resulted in oxacillin susceptibility in OS-MRSA, while loss of the bla regulator restored oxacillin resistance. The bla system plays a crucial role in regulating oxacillin susceptibility in OS-MRSA isolates.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Review
Chemistry, Multidisciplinary
Ciaran P. Seath, Aaron D. Trowbridge, Tom W. Muir, David W. C. MacMillan
Summary: Biomolecular interactions are crucial for cellular processes, with a focus on protein-protein interactions playing a key role in cellular signaling pathways. Recent advancements in creating reactive intermediates that cross-link neighboring proteins have provided insights into the biomolecular makeup of cellular environments, accelerating the understanding of PPIs and their impact on cellular physiology.
CHEMICAL SOCIETY REVIEWS
(2021)
Article
Infectious Diseases
Shizhou Wu, Junqi Zhang, Qi Peng, Yunjie Liu, Lei Lei, Hui Zhang
Summary: Antibiotic resistance, particularly in MRSA infections, is a serious global health concern with significant social and financial consequences. The YycFG two-component signal transduction system in Staphylococcus aureus is crucial for bacterial viability and plays a key role in cell membrane metabolism, cell wall synthesis, and biofilm formation. Inhibition of the YycFG pathway shows promise as a potential target for managing MRSA-induced infections by reducing biofilm formation and bacterial pathogenicity.
Article
Plant Sciences
Xiying Wu, Guang-Lei Ma, Hao-Wei Chen, Ze-Yu Zhao, Zi-Ping Zhu, Juan Xiong, Guo-Xun Yang, Jin-Feng Hu
Summary: This study investigated the antibacterial and antibiofilm activities of Euphorbia humifusa and identified compounds that exhibited strong inhibitory effects against Staphylococcus aureus. These compounds disrupted cell integrity, increased membrane permeability, and down-regulated biofilm-related gene expression. These findings provide support for the traditional use of Euphorbia humifusa in the treatment of furuncles and carbuncles and highlight its potential as a source for producing promising antibiofilm alternatives against Staphylococcus aureus.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Biochemical Research Methods
Benjamin S. Johnson, Lexie Chafin, Daniela Farkas, Jessica Adair, Ajit Elhance, Laszlo Farkas, Joseph S. Bednash, James D. Londino
Summary: This study modified the structure of BioID2 to create a smaller and more efficient biotin ligase called MicroID2. Compared to other biotin ligases, MicroID2 demonstrated higher labeling activity and lower background labeling. Additionally, a mutant of MicroID2 called lbMi-croID2 was developed for experiments requiring precise temporal control of labeling. Finally, the utility of MicroID2 in mass spectrometry experiments was demonstrated.
MOLECULAR & CELLULAR PROTEOMICS
(2022)
Article
Microbiology
Thomas A. Russo, Ulrike Carlino-MacDonald, Cassandra L. Alvarado, Connor J. Davies, Oscar Barnes, Grishma Trivedi, Parijat Mathur, Alan Hutson, Felise G. Adams, Maoge Zang, Alice Ascari, Bart A. Eijkelkamp
Summary: This study explores new classes of antimicrobials for carbapenem-resistant Acinetobacter baumannii and identifies penicillin binding protein 7/8 (PBP 7/8) as a high-value drug target. Experimental results demonstrate the essential role of PBP 7/8 in the growth and survival of A. baumannii.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Review
Pharmacology & Pharmacy
Varsha Naidu, Amelia Bartczak, Anthony J. Brzoska, Peter Lewis, Bart A. Eijkelkamp, Ian T. Paulsen, Liam D. H. Elbourne, Karl A. Hassan
Summary: This study investigated the origins and evolution of the AdeABC, AdeFGH, and AdeIJK efflux pumps in the Acinetobacter genus. The results showed that AdeIJK has been present in Acinetobacter genomes since the beginning of this genus, while AdeABC and AdeFGH were found in less than half of the species and showed some lineage specificity. The organization and genetic contexts of adeABC loci varied extensively, suggesting frequent recombination events. The presence of regulatory systems associated with the pumps was almost always observed in the genomes of species encoding the pumps. Mutations in the repressor gene adeN were selected by antibiotic exposure, indicating antibiotic-driven evolution of the AdeABC pump.
DRUG RESISTANCE UPDATES
(2023)
Article
Biochemistry & Molecular Biology
Alexander J. Anderson, Jordan J. Crameri, Ching-Seng Ang, Tess R. Malcolm, Yilin Kang, Megan J. Baker, Catherine S. Palmer, Alice J. Sharpe, Luke E. Formosa, Katherine Ganio, Michael J. Baker, Christopher A. McDevitt, Michael T. Ryan, Megan J. Maher, Diana Stojanovski
Summary: Human Tim8a and Tim8b proteins are involved in the assembly of cytochrome c oxidase (Complex IV). They interact with intermediate-assembly subcomplexes of Complex IV and are proposed to be auxiliary assembly factors in the formation of the Complex IV S3 subcomplex. The importance of human cells encoding two Tim8 proteins and their precise molecular function(s) are still unclear.
Article
Biochemistry & Molecular Biology
Tina H. Dao, Amy Iverson, Stephanie L. Neville, Michael D. L. Johnson, Christopher A. McDevitt, Jason W. Rosch
Summary: Maintenance of intracellular metal homeostasis is crucial for bacterial pathogens during interaction with host niches. Streptococci, despite lacking copper-utilizing proteins, can accumulate significant levels of copper. Loss of copper-specific exporter CopA in Streptococcus pyogenes strain HSC5 leads to increased copper sensitivity, reduced viability during stationary phase cultivation, and attenuation during murine soft-tissue infection.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Claudia A. Blindauer, Christopher A. McDevitt
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Ram P. Maharjan, Geraldine J. Sullivan, Felise G. Adams, Bhumika S. Shah, Jane Hawkey, Natasha Delgado, Lucie Semenec, Hue Dinh, Liping Li, Francesca L. Short, Julian Parkhill, Ian T. Paulsen, Lars Barquist, Bart A. Eijkelkamp, Amy K. Cain
Summary: Using functional genomics, we have identified the transcriptional regulator DksA as a master regulator for broad stress protection and virulence in Acinetobacter baumannii. DksA controls various aspects such as ribosomal protein expression, metabolism, mutation rates, desiccation, antibiotic resistance, and host colonization. This study lays the groundwork for understanding the role of DksA as a major regulator in stress response and virulence in this important pathogen.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Microbiology
Charlie Higgs, Lamali Sadeesh Kumar, Kerrie Stevens, Janet Strachan, Tony Korman, Kristy Horan, Diane Daniel, Madeline Russell, Christopher A. Mcdevitt, Norelle L. Sherry, Timothy P. Stinear, Benjamin P. Howden, Claire L. Gorrie
Summary: Streptococcus pneumoniae is an important human pathogen, and non-invasive isolates may serve as a source of invasive isolates and reservoirs of antimicrobial resistance (AMR) determinants. By comparing the genomes and antibiotic resistance profiles of invasive and non-invasive isolates, we found that non-invasive isolates exhibited higher levels of resistance to multiple antibiotics and certain sub-populations with high levels of AMR were overrepresented in the non-invasive population.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Chemistry, Inorganic & Nuclear
Jacob A. Rowan, Stacey E. Rudd, Katherine Ganio, Christopher A. McDevitt, Jonathan M. White, Paul S. Donnelly
Summary: This research investigates the potential of using acyclic tetrapyrrolic 2,2'-bisdipyrrins as ligands to prepare charge-neutral, lipophilic, cell-permeable, redox active complexes with positron-emitting copper-64. The synthesis and characterization of a series of tetrapyrrolic 2,2'-bisdipyrrin copper(II) complexes are reported, and the electrochemical properties of the complexes are investigated. The copper(II) complexes are cell-permeable in A431 mammalian cells and can be radiolabeled with copper-64 at room temperature.
INORGANIC CHEMISTRY
(2023)
Article
Microbiology
Liam K. R. Sharkey, Romain Guerillot, Calum J. Walsh, Adrianna M. Turner, Jean Y. H. Lee, Stephanie L. Neville, Stephan Klatt, Sarah L. Baines, Sacha J. Pidot, Fernando J. Rossello, Torsten Seemann, Hamish E. G. Mcwilliam, Ellie Cho, Glen P. Carter, Benjamin P. Howden, Christopher A. Mcdevitt, Abderrahman Hachani, Timothy P. Stinear, Ian R. Monk
Summary: This study provides insights into the functionality of the WalKR regulon in Staphylococcus aureus, highlighting its crucial role in cell wall homeostasis, purine biosynthesis, protein biosynthesis, and DNA replication. These findings underscore the potential of WalKR as a target for novel anti-staphylococcal therapeutics.
Article
Chemistry, Medicinal
Maytham Hussein, Rafah Allobawi, Jinxin Zhao, Heidi Yu, Stephanie L. Neville, Jonathan Wilksch, Labell J. M. Wong, Mark Baker, Christopher A. McDevitt, Gauri G. Rao, Jian Li, Tony Velkov
Summary: This study employed integrated metabolomics and transcriptomics methods to investigate the molecular mechanisms of ceftazidime/avibactam against a pan-drug-resistant K. pneumoniae clinical isolate. The study found that ceftazidime/avibactam induced time-dependent perturbations in the bacterium's metabolome and transcriptome, with notable effects at 6 hours. Ceftazidime/avibactam affected cell envelope biogenesis and central carbon metabolism, providing insights into the antibacterial and resistance mechanisms of the antibiotic.
ACS INFECTIOUS DISEASES
(2023)
Article
Chemistry, Medicinal
Alice Ascari, Jack K. Waters, Renato Morona, Bart A. Eijkelkamp
Summary: Shigella flexneri, the primary causative agent of worldwide shigellosis, employs adaptations through the expression of VL-Oag LPS to resist antimicrobial FAs, while becoming susceptible to DOC stress. This study highlights the significance of maintaining appropriate regulation of cell envelope constituents, particularly VL-Oag LPS, for S. flexneri to adapt to diverse stresses during infection.
ACS INFECTIOUS DISEASES
(2023)
Meeting Abstract
Biophysics
Hugo MacDermott-Opeskin, Katie A. Wilson, Bart Eijkelkamp, Megan L. O'Mara
BIOPHYSICAL JOURNAL
(2023)
Article
Microbiology
Alice Ascari, Sonja Froelich, Maoge Zang, Elizabeth N. H. Tran, Danny W. Wilson, Renato Morona, Bart A. Eijkelkamp
Summary: This study reveals that Shigella flexneri undergoes changes in cell envelope composition and surface-associated glycolipids during infection, affecting its interaction with host fatty acids and maintaining virulence. It also demonstrates that S. flexneri induces major host lipid remodeling and suggests that fatty acid supplementation can influence the persistence and magnitude of infection.
JOURNAL OF BACTERIOLOGY
(2023)
Article
Biochemical Research Methods
Raquel Gonzalez de Vega, David Clases, Bliss A. Cunningham, Katherine Ganio, Stephanie L. Neville, Christopher A. McDevitt, Philip A. Doble
Summary: This study investigates the interplay between d-block metal ions and their associated biomolecules in response to invading pathogens. By using elemental techniques, the researchers were able to quantify both the distribution of trace elements and the abundance of specific transport proteins. The findings demonstrate the potential of a single instrumental platform for multiplex analyses, which can be applied to investigate complex elemental interactions and aid in the development of new therapeutic approaches.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Article
Microbiology
David M. P. De Oliveira, Brian M. Forde, Minh-Duy Phan, Bernhard Steiner, Bing Zhang, Johannes Zuegg, Ibrahim M. El-Deeb, Gen Li, Nadia Keller, Stephan Brouwer, Nichaela Harbison-Price, Amanda J. Cork, Michelle J. Bauer, Saleh F. Alquethamy, Scott A. Beatson, Jason A. Roberts, David L. Paterson, Alastair G. McEwan, Mark A. T. Blaskovich, Mark A. Schembri, Christopher A. McDevitt, Mark von Itzstein, Mark J. Walker
Summary: The study found that the combination of PBT2 and zinc with tetracycline class antibiotics can effectively combat multidrug-resistant A. baumannii, potentially serving as a treatment for overcoming strain resistance.