Article
Biochemistry & Molecular Biology
Francesco Bisiak, Adriana Chrenkova, Sheng-Da Zhang, Jannik N. Pedersen, Daniel E. Otzen, Yong E. Zhang, Ditlev E. Brodersen
Summary: The bacterial stringent response involves metabolic reprogramming to increase long-term survivability under stress conditions. The production and degradation of alarmones, modified nucleotides that affect cellular pathways, depend on enzymes from the RelA/SpoT family. Crystal structures of small alarmone hydrolases (SAHs) from two bacteria show that structural differences in substrate access and dimer conformations regulate their activity.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Immunology
Grace Kago, Charles L. Turnbough Jr, Juan Carlos Salazar, Shelley M. Payne
Summary: This study reveals the importance of (p)ppGpp synthesis in the virulence and adaptation of Shigella flexneri. Disrupting (p)ppGpp synthesis diminishes the expression of key virulence genes, reduces bacterial invasion and intercellular spread. The study also highlights the role of (p)ppGpp in maintaining the infection and spread of S. flexneri in the intracellular environment.
INFECTION AND IMMUNITY
(2023)
Article
Biochemistry & Molecular Biology
Wieland Steinchen, Shehryar Ahmad, Martina Valentini, Kira Eilers, Mohamad Majkini, Florian Altegoer, Marcus Lechner, Alain Filloux, John C. Whitney, Gert Bange
Summary: The study reveals that the P. aeruginosa SAH enzyme can hydrolyze (p)ppGpp and (p)ppApp in a strictly manganese-dependent manner, and its enzymatic activity is required for biofilm formation. Moreover, the hydrolysis of (p)ppApp by SAH provides protection against the T6SS.
MOLECULAR MICROBIOLOGY
(2021)
Article
Microbiology
Can Huang, Jiao Meng, Wenqian Li, Jingyu Chen
Summary: This study investigated the role of stringent response in Yersinia enterocolitica, a typical foodborne pathogen, and found that (p)ppGpp and DksA have synergistic and independent roles in regulating gene expression and phenotypes of Y. enterocolitica. Gene expression analysis revealed that (p)ppGpp and DksA deficiency reduced the transcription of flagellar synthesis genes and biofilm synthesis genes, which could potentially contribute to changes in motility and biofilm formation.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Augusto Cesar Hunt-Serracin, Misha Kazi, Joseph M. Boll, Cara C. Boutte
Summary: The stringent factor Rel in Mycobacterium abscessus (Mab), a nontuberculous mycobacterial pathogen, does not play a significant role in (p)ppGpp synthesis and does not provide survival advantages in stress conditions or antibiotic treatment. However, it is involved in regulating expression of anabolism and growth genes in the stationary phase. This study suggests the presence of an unannotated (p)ppGpp synthetase in Mab.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rosa Luisa Ambrosio, Catalina Ana Rossello, Doralicia Casares, Gianna Palmieri, Aniello Anastasio, Pablo Escriba
Summary: Since the misuse of antibiotics has led to drug resistance, the search for alternative antimicrobial substances has become crucial. Antimicrobial peptide 1018-K6 has shown significant bactericidal and antibiofilm activity against various pathogenic bacteria, including antibiotic-resistant strains.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Yudai Tabuchi, Takahito Watanabe, Riku Katsuki, Yuji Ito, Masumi Taki
Summary: A covalent binder for a target protein was obtained by screening a peptide library on the T7 phage, with activation of the warhead only in the specific microenvironment created between the target protein and an appropriate peptide during the selection process.
CHEMICAL COMMUNICATIONS
(2021)
Article
Nanoscience & Nanotechnology
Song- Han, Deborah A. Sarkes, Margaret M. Hurley, Rebecca Renberg, Can Huang, Yuwen Li, Justin P. Jahnke, James J. Sumner, Dimitra N. Stratis-Cullum, Arum Han
Summary: Discovery of microorganisms and their relevant surface peptides that specifically bind to target materials can be achieved through iterative biopanning-based screening. Recently, microfluidics-based biopanning methods have been developed to overcome the limitations of conventional methods. In this work, a magnetophoretic microfluidic biopanning platform was developed to isolate microorganisms that bind to gold, and successful screening of bacterial peptide display library and soil microbes was demonstrated.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Microbiology
David K. O'Brien, Wilson J. Ribot, Donald J. Chabot, Angelo Scorpio, Steven A. Tobery, Tanya M. Jelacic, Zhibin Wu, Arthur M. Friedlander
Summary: The capsule of Bacillus anthracis plays a protective role in preventing the antimicrobial activity of cationic AMPs, which contributes to immune evasion and virulence.
Review
Biochemistry & Molecular Biology
Jay Yang, Yudai Tabuchi, Riku Katsuki, Masumi Taki
Summary: Monoclonal antibody therapies have made significant impact in various areas, but they have limitations. Peptides and nucleic acid aptamers have been proposed as alternatives, but their short in vivo half-life is a limitation. Covalent drugs, which form permanent bonds with target proteins, could overcome this limitation, but their potential side effects have slowed their acceptance. The TCI platform is broadening to include larger biomolecules with desirable properties, and this review discusses the development of TCI made of bio-oligomers/polymers obtained by rational design and combinatorial screening. The authors hope to highlight the TCI platform as a realistic replacement for antibodies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Orthopedics
Yuanli Li, Junlan Nie, Changgong Deng, Hong Li
Summary: This study found that P-15 peptide can mitigate chondrocyte damage and osteoarthritis progression by inhibiting cell death and modulating the SFPQ-Akt-RUNX2 pathway, offering an opportunity to develop new strategies for the treatment of osteoarthritis.
JOURNAL OF ORTHOPAEDIC SURGERY AND RESEARCH
(2023)
Article
Cell & Tissue Engineering
Hao Chen, Yaodong Zhou, Qirong Dong
Summary: In this study, the intermolecular recognition and interaction between BMP proteins and the BRI receptor were systematically examined. The results showed that the BRI-binding site consists of three hotspot regions and the binding affinity can be improved by cyclization strategy.
CELLULAR AND MOLECULAR BIOENGINEERING
(2022)
Article
Biochemistry & Molecular Biology
Che Wang, Lili Huang, Ruojin Li, Ying Wang, Xiaoxue Wu, Dejing Shang
Summary: The cationic anticancer peptide L-K6 showed MDR reversal potential by inhibiting P-gP function in DOX-resistant breast cancer cells, leading to increased intracellular accumulation of DOX and a promising synergistic anticancer activity against MDR cancer.
INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS
(2021)
Article
Microbiology
Mariliis Hinnu, Marta Putrins, Karin Kogermann, Dirk Bumann, Tanel Tenson
Summary: This study demonstrates that the decrease in the minimum inhibitory concentration (MIC) of azithromycin triggered by bicarbonate is solely attributed to the alkalization caused by insufficiently buffered media, and bicarbonate is unlikely to alter the activity of efflux pumps.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Aleksandr Ianevski, Ronja M. Simonsen, Vegard Myhre, Tanel Tenson, Valentyn Oksenych, Magnar Bjoras, Denis E. Kainov
Summary: Viruses can cause outbreaks in humans and have economic and health burdens. Broad-spectrum antivirals (BSAs) and BSA-containing drug combinations (BCCs) are immediate therapeutic options for virus identification and vaccine development. DrugVirus.info 2.0 provides an integrative portal for exploration and analysis of BSAs and BCCs, expanding the database and functionality for antiviral drug development.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Aleksandr Ianevski, Rouan Yao, Ronja M. Simonsen, Vegard Myhre, Erlend Ravlo, Gerda D. Kaynova, Eva Zusinaite, Judith M. White, Stephen J. Polyak, Valentyn Oksenych, Marc P. Windisch, Qiuwei Pan, Egle Lastauskiene, Astra Vitkauskiene, Algimantas Matukevicius, Tanel Tenson, Magnar Bjoras, Denis E. Kainov
Summary: This article reviews druggable virus-host interactions, mechanisms of action, immunomodulatory properties, delivery routes, and interactions of broad-spectrum antivirals (BSAs) with other antivirals. It suggests expanding the indications of BSAs and developing new pan- and cross-viral mono- and combinational therapies. The article also introduces a new scoring algorithm to prioritize the development of promising BSAs and BSA-containing drug cocktails (BCCs) during the critical period between the identification of a new virus and the development of specific treatments.
Article
Dermatology
Helen Vaher, Kristiina Kingo, Peep Kolberg, Martin Pook, Liisi Raam, Anet Laanesoo, Anu Remm, Tanel Tenson, Kaur Alasoo, Ulrich Mrowietz, Stephan Weidinger, Kulli Kingo, Ana Rebane
Summary: The study confirms the alteration in expression of IL-1 family cytokines and inflammasome-related genes in the development of atopic dermatitis (AD), and a positive relationship between NLRP1 and IL1B or IL18 mRNA levels. It also demonstrates increased expression of NLRP1 and PYCARD proteins, and increased caspase-1 activity in the skin of AD patients. Additionally, genetic associations with AD and the involvement of various immune cell types are predicted. In keratinocytes, colonization with Staphylococcus aureus results in increased secretion of IL-1b and IL-18, which is inhibited by siRNA silencing of NLRP1. These findings suggest that S. aureus colonization may activate the NLRP1 inflammasome in keratinocytes, leading to the secretion of IL-1b and IL-18, and contributing to the pathogenesis of AD, particularly in the presence of genetic variations in the IL-18 pathway.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Medicine, Research & Experimental
Kairi Lorenz, Liis Preem, Kadi Sagor, Marta Putrins, Tanel Tenson, Karin Kogermann
Summary: Increasing evidence suggests that chronic wounds are associated with bacterial biofilms. New wound care products are being developed to inhibit biofilm formation and treat existing ones. In order to analyze these new antibacterial drug delivery systems, standardized assays and appropriate tools and models are needed. This study demonstrates that optimized in vitro and ex vivo wound infection and biofilm models provide a convenient approach for testing the antibacterial and antibiofilm properties of novel wound dressings. The results can be used to design more effective wound care products and screen different formulations and active substances.
MOLECULAR PHARMACEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Hedvig Tamman, Karin Ernits, Mohammad Roghanian, Andres Ainelo, Christina Julius, Anthony Perrier, Ariel Talavera, Hanna Ainelo, Remy Dugauquier, Safia Zedek, Aurelien Thureau, Javier Perez, Gipsi Lima-Mendez, Regis Hallez, Gemma C. Atkinson, Vasili Hauryliuk, Abel Garcia-Pino
Summary: Stringent factors regulate bacterial cell reprogramming by increasing the level of (p)ppGpp. This study presents the crystal structure of the hydrolase-only SpoT from Acinetobacter baumannii and reveals the intramolecular regulation mechanism of 'long'-stringent factors. The Core subdomain plays a key role in determining the specialization of long RelA-SpoT homologs towards synthesis or hydrolysis.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Andres Ainelo, Julien Caballero-Montes, Ondrej Bulvas, Karin Ernits, Kyo Coppieters't Wallant, Hiraku Takada, Sophie Z. Craig, Gabriel Mazzucchelli, Safia Zedek, Iva Pichova, Gemma C. Atkinson, Ariel Talavera, Chloe Martens, Vasili Hauryliuk, Abel Garcia-Pino
Summary: In this study, the crystal structure of the DarB2:RelNTD2 complex was determined to uncover how DarB interacts with the SYNTH domain of Rel to stimulate (p)ppGpp synthesis directly. Binding to c-di-AMP rigidifies DarB, imposing an entropic penalty that precludes DarB-mediated control of Rel during normal growth. These experiments provide insights into the allosteric regulation mechanism of Rel stringent factors independent of amino acid starvation.
Article
Biochemistry & Molecular Biology
Nozomu Obana, Hiraku Takada, Caillan Crowe-McAuliffe, Mizuki Iwamoto, Artyom A. Egorov, Kelvin J. Y. Wu, Shinobu Chiba, Victoriia Murina, Helge Paternoga, Ben I. C. Tresco, Nobuhiko Nomura, Andrew G. Myers, Gemma C. Atkinson, Daniel N. Wilson, Vasili Hauryliuk
Summary: This study investigates genome-encoded antibiotic resistance ABC proteins from different bacteria and discovers their resistance spectrum and mechanisms, which are important for understanding the diversity of intrinsic antibiotic resistance in bacteria.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Engineering, Environmental
Veljo Kisand, Peeter Laas, Kadi Palmik-Das, Kristel Panksep, Helen Tammert, Leena Albreht, Hille Allemann, Lauri Liepkalns, Katri Vooro, Christian Ritz, Vasili Hauryliuk, Tanel Tenson
Summary: Taking advantage of Estonia's small size and population, a wastewater-based epidemiology approach was used to monitor the spread of SARS-CoV-2, with weekly nation-wide updates released. Results showed that the concentration of the virus in wastewater correlated with the number of COVID-19 infections in the population, and the increase in virus concentration preceded the increase in positive cases by approximately 1.25 weeks (9 days). The surveillance system in Estonia helped inform public health policies and interventions during the COVID-19 pandemic.
Article
Biochemistry & Molecular Biology
Taavi Pall, Hannes Luidalepp, Tanel Tenson, Ulo Maivali
Summary: We evaluated the quality of inferential statistics in the field of differential expression profiling using high-throughput sequencing (HT-seq) by analyzing datasets submitted to the NCBI GEO data repository from 2008 to 2020. Our findings indicate widespread bias and unreliability of statistical methods used to analyze HT-seq data. Only a small percentage of experiments resulted in expected p-value distributions, and many experiments showed indications of differential expression despite assumptions that most genes are not differentially expressed. The choice of differential expression analysis program also influenced the observed patterns.
Article
Microbiology
Anna Maria Giuliodori, Riccardo Belardinelli, Melodie Duval, Raffaella Garofalo, Emma Schenckbecher, Vasili Hauryliuk, Eric Ennifar, Stefano Marzi
Summary: Escherichia coli CspA is an RNA binding protein that stimulates translation, including its own, during cold-shock. It specifically promotes the translation of cspA mRNA at low temperature by interacting with the folded conformation less accessible to the ribosome without inducing large structural rearrangements. This interaction allows the progression of ribosomes during the transition from translation initiation to elongation, and a similar mechanism may be responsible for CspA-dependent translation stimulation observed with other probed mRNAs.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Janani Durairaj, Andrew M. Waterhouse, Toomas Mets, Tetiana Brodiazhenko, Minhal Abdullah, Gabriel Studer, Gerardo Tauriello, Mehmet Akdel, Antonina Andreeva, Alex Bateman, Tanel Tenson, Vasili Hauryliuk, Torsten Schwede, Joana Pereira
Summary: The AlphaFold database provides millions of predicted protein structures, covering almost all known proteins. By utilizing deep learning techniques, these structures can be accurately predicted, shedding light on the functions and roles of these proteins in biology. This study further explores the discovery of new protein families through these predicted structures.
Article
Biochemical Research Methods
Lucia Dominguez-Molina, Ariel Talavera, Albinas Cepauskas, Tatsuaki Kurata, Dannele Echemendia-Blanco, Vasili Hauryliuk, Abel Garcia-Pino
Summary: This study reports the production, biophysical analysis, and crystallization of the aTfaRel2/faRel2 operon from Coprobacillus sp. D7, which encodes a bicistronic type II toxin-antitoxin module. The structures of the antitoxin ATfaRel2, toxin FaRel2, and the ATfaRel2-FaRel2 complex were determined through crystallography. These findings provide insights into the structure and function of this TA module.
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS
(2023)
Article
Infectious Diseases
Tetiana Brodiazhenko, Kathryn Jane Turnbull, Kelvin J. Y. Wu, Hiraku Takada, Ben I. C. Tresco, Tanel Tenson, Andrew G. Myers, Vasili Hauryliuk
Summary: In this study, we found that the newly developed lincosamide iboxamycin showed high activity against Listeria monocytogenes and could overcome the resistance caused by VgaL/Lmo0919 ABCF ATPase. Iboxamycin displayed a pronounced post-antibiotic effect and showed potential as a novel antilisterial agent. However, the emergence and spread of ABCF ARE variants capable of defeating next-generation lincosamides should be closely monitored.
JAC-ANTIMICROBIAL RESISTANCE
(2022)