Article
Biochemistry & Molecular Biology
Patricia Coelho, Joana Oliveira, Iva Fernandes, Paula Araujo, Ana Rita Pereira, Paula Gameiro, Lucinda J. Bessa
Summary: Bacterial quorum sensing is a communication system that regulates various bacterial mechanisms, including biofilm formation. Targeting microbial QS is considered as an alternative strategy to combat multidrug-resistant pathogens, with phytochemicals showing potential QS interference activity. An extract and a compound of bioinspired origin were tested for their ability to inhibit biofilm formation and interfere with QS-related gene expression in Pseudomonas aeruginosa and Staphylococcus aureus. The results showed significant effects on biofilm formation and gene expression in S. aureus strains, suggesting potential therapeutic applications for these anti-QS molecules.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Yufang Li, Shijun Li, Kun Yang, Rongxiang Guo, Xin Zhu, Yanan Shi, Aixiang Huang
Summary: The study revealed the significant antibiofilm activity of a novel milk-derived antimicrobial peptide BCp12 against Staphylococcus aureus through interfering with the agr QS system, demonstrating its potential as a novel antibiofilm agent in the food industry.
JOURNAL OF APPLIED MICROBIOLOGY
(2022)
Article
Microbiology
Soyoun Park, Adam Classen, Hanny Maeva Gohou, Roberto Maldonado, Emily Kretschmann, Chloe Duvernay, Geun-Joong Kim, Jennifer Ronholm
Summary: A new plasmid-based screening method was used to identify bacteria with antagonistic activity against antibiotic-resistant Staphylococcus aureus. By creating stable recombinant plasmids carrying reporter proteins under the control of a S. aureus promoter, the study successfully identified commensal bacteria with growth-inhibiting and quorum-quenching activity. This approach offers a promising strategy for developing probiotic drugs and therapeutics for S. aureus infections in both humans and animals.
Review
Biochemistry & Molecular Biology
Bhawandeep Kaur, Jeena Gupta, Sarika Sharma, Divakar Sharma, Sandeep Sharma
Summary: Staphylococcus aureus is a common pathogen causing various infections, with Methicillin-Resistant Staphylococcus aureus (MRSA) being particularly concerning. The primary antimicrobial resistance mechanisms in S. aureus involve efflux pumps and biofilm formation, with quorum sensing and drug efflux playing crucial roles. Efflux pump inhibitors (EPIs) have been identified as a promising approach to combat bacterial resistance, by inhibiting drug efflux mechanisms and transport of quorum sensing signalling molecules.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Review
Biochemistry & Molecular Biology
Michael Otto
Summary: Staphylococcus aureus is a significant pathogen responsible for numerous infections and causing high mortality rates in hospitalized patients. The emergence of antibiotic resistance, particularly methicillin-resistant S. aureus (MRSA), has prompted the exploration of alternative anti-virulence strategies. Targeting the S. aureus accessory gene regulator (Agr) quorum-sensing system, a key regulator of virulence, has been proposed as the most common anti-virulence approach. However, there is limited in vivo evidence for the efficacy of Agr inhibition, and potential concerns regarding biofilm formation and functional implications on invasive S. aureus infections.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jovana Bakovic, Bess Yi Kun Yu, Daniel Silva, Maria Baczynska, Sew Yeu Peak-Chew, Amy Switzer, Lynn Burchell, Sivaramesh Wigneshweraraj, Muralidharan Vandanashree, Balasubramanian Gopal, Valeriy Filonenko, Mark Skehel, Ivan Gout
Summary: S. aureus AgrA is modified by covalent binding of CoA in response to oxidative or metabolic stress, leading to decreased DNA-binding activity.
Article
Biochemistry & Molecular Biology
Macauley J. Green, Ewan J. Murray, Paul Williams, Amir M. Ghaemmaghami, Jonathan W. Aylott, Philip M. Williams
Summary: Under low-shear modeled microgravity conditions, Staphylococcus aureus exhibited a colonization phenotype instead of a pathogenic one, due to reduced production of autoinducing peptide signal molecules.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Adam Benedict Turner, Erik Gerner, Rininta Firdaus, Maite Echeverz, Maria Werthen, Peter Thomsen, Sofia Almqvist, Margarita Trobos
Summary: The study investigated the impact of sodium salicylate (NaSa) on Staphylococcus aureus quorum sensing (QS), virulence production, and biofilm formation. NaSa was found to downregulate the agr QS system, leading to decreased toxin secretion and increased biofilm formation. The effect of NaSa on biofilm formation was dependent on the strain and material surface. The study suggests that NaSa could be a potential alternative or adjuvant to traditional antibiotics.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Microbiology
Norhan H. Mahdally, Riham F. George, Mona T. Kashef, Medhat Al-Ghobashy, Fathia E. Murad, Ahmed S. Attia
Summary: The development of a compound named staquorsin as an Agr inhibitor for Staphylococcus aureus showed promising results in inhibiting virulence factors without affecting bacterial viability. In in vitro and in vivo testing, the compound effectively controlled the infection and demonstrated potential as a drug candidate against S. aureus.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Microbiology
Morgan M. Severn, Michael R. Williams, Ali Shahbandi, Zoie L. Bunch, Laurie M. Lyon, Amber Nguyen, Livia S. Zaramela, Daniel A. Todd, Karsten Zengler, Nadja B. Cech, Richard L. Gallo, Alexander R. Horswill
Summary: Human skin is home to a variety of commensal bacteria, including Staphylococcus hominis, which plays an important role in preventing Staphylococcus aureus colonization and infection. It produces multiple signaling molecules that inhibit the virulence factor regulation system of S. aureus and other related species. Synthetic versions of these molecules have shown protective effects against S. aureus-associated skin injuries in animal models.
Article
Microbiology
Jeong Eun Lee, Shinwon Lee, Sohee Park, Soon O. Lee, Sun H. Lee
Summary: This study found that dysfunctional accessory gene regulator (agr) is associated with higher mortality in invasive methicillin-resistant Staphylococcus aureus infections. However, the association between agr dysfunction and mortality in methicillin-susceptible Staphylococcus aureus bacteremia (MSSA-B) was not significant. The functionality of agr in causative organisms may impact patients' outcomes in MSSA-B with moderate severity.
MICROBIOLOGY SPECTRUM
(2021)
Article
Multidisciplinary Sciences
Mohammed Y. Refai, Ahmed M. Elazzazy, Mohammed Abu-Elghait, Said Desouky, Mona O. I. Albureikan, Jiro Nakayama
Summary: This study found that Ziziphus spina-christi leaf extract (ZSCLE) inhibits the agr quorum sensing (QS) system and the phenotypic blood hemolytic activity in Staphylococcus aureus. The diethyl ether fraction was identified as the most effective inhibitor. Phytochemical analysis showed that the total extract contains a high number of flavonoids and other compounds.
ARABIAN JOURNAL FOR SCIENCE AND ENGINEERING
(2023)
Article
Food Science & Technology
Magdalena Gonet, Daniel Krowarsch, Justyna Schubert, Aleksandra Tabis, Jacek Bania
Summary: The SECepi and SELepi produced by S. epidermidis show similar resistance to proteolysis compared to their orthologues produced by S. aureus. The SELs produced by S. epidermidis are more resistant to proteolysis with trypsin, while the SECepi produced by S. epidermidis is more resistant to thermal denaturation compared to its S. aureus orthologues. These findings suggest that the enterotoxins SECepi and SELepi produced by S. epidermidis may pose a food safety risk comparable to those produced by S. aureus.
FOODBORNE PATHOGENS AND DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Maan T. Khayat, Hisham A. Abbas, Tarek S. Ibrahim, Ahdab N. Khayyat, Majed Alharbi, Khaled M. Darwish, Sameh S. Elhady, El-Sayed Khafagy, Martin K. Safo, Wael A. H. Hegazy
Summary: The development of bacterial resistance to traditional antibiotics is a growing public health concern, but targeting bacterial virulence may offer a solution. Antivirulence agents that do not induce resistance could be promising for treating resistant bacterial infections. Sitagliptin, among other gliptins, shows efficient antibiofilm and antivirulence activities against Pseudomonas aeruginosa and Staphylococcus aureus, making it a potentially valuable addition to antibiotic treatments.
Article
Biotechnology & Applied Microbiology
Mohammed Y. Refai, Ahmed M. Elazzazy, Said E. Desouky, Mohammed Abu-Elghait, Eman A. Fayed, Sulaiman M. Alajel, Abdullah A. Alajlan, Mona O. Albureikan, Jiro Nakayama
Summary: Quorum sensing inhibitors (QSI) are anti-virulence agents that disarm pathogens of their virulence rather than killing them. Ambuic acid and Synerazol, two epoxide compounds, have been found to efficiently block the quorum sensing systems in Gram-positive bacteria.
Article
Obstetrics & Gynecology
Fiona K. Smith, Ijeoma Agu, Shivani Murarka, Gazala Siddiqui, Francisco J. Orejuela, Tristi W. Muir, Danielle D. Antosh
Summary: This study found that there are differences in barriers to care for patients presenting to urogynecologists in private and public healthcare settings. Patients in private settings were mainly hindered by not knowing how to see a specialist, while patients in public settings were hindered by inability to get a closer appointment time. Additionally, patients in public settings were more likely to cite lack of health care coverage as a barrier to care.
FEMALE PELVIC MEDICINE AND RECONSTRUCTIVE SURGERY
(2021)
Correction
Biochemistry & Molecular Biology
Matthew J. McBride, Nazar Mashtalir, Evan B. Winter, Hai T. Dao, Martin Filipovski, Andrew R. D'Avino, Hyuk-Soo Seo, Neil T. Umbreit, Roodolph St Pierre, Alfredo M. Valencia, Kristin Qian, Hayley J. Zullow, Jacob D. Jaffe, Sirano Dhe-Paganon, Tom W. Muir, Cigall Kadoch
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Aiwei Wu, Junhong Zhi, Tian Tian, Ali Cihan, Murat A. Cevher, Ziling Liu, Yael David, Tom W. Muir, Robert G. Roeder, Ming Yu
Summary: The study showed that DOT1L depletion in erythroleukemic cells does not affect the elongation rate of RNA polymerase II, but plays a significant role in transcription initiation by regulating the recruitment of transcription factor IID along with ENL. This is achieved by enhancing H2Bub1 levels and limiting the recruitment of the SAGA complex. These findings provide new insights into the role of the DOT1L complex in transcriptional regulation and its implications for MLLr leukemias.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Nazar Mashtalir, Hai T. Dao, Akshay Sankar, Hengyuan Liu, Aaron J. Corin, John D. Bagert, Eva J. Ge, Andrew R. D'Avino, Martin Filipovski, Brittany C. Michel, Geoffrey P. Dann, Tom W. Muir, Cigall Kadoch
Summary: This study identified the effects of chromatin features on mSWI/SNF activities and interactions, as well as the combinatorial contributions of complex module components, reader domains, and nucleosome engagement properties to the localization of complexes.
Review
Biochemistry & Molecular Biology
Antony J. Burton, Ghaith M. Hamza, Andrew X. Zhang, Tom W. Muir
Summary: Protein-protein interactions in the nucleus are crucial for transcriptional regulation and genomic stability, with epigenetic proteins being identified as key therapeutic targets for diseases. Recent advances in chemical biology and mass spectrometry techniques have greatly improved our understanding of histone-mediated protein interactions.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Article
Chemistry, Multidisciplinary
Hai T. Dao, Hengyuan Liu, Nazar Mashtalir, Cigall Kadoch, Tom W. Muir
Summary: This study reports a strategy for controlling the orientation of asymmetric nucleosomes and hexasomes, providing an efficient method for studying gene regulation. By using truncated DNA templates and DNA ligation, the researchers successfully prepared desymmetrized mononucleosomes and oligonucleosomes with varied DNA sequences and histone compositions. Using this technology, they investigated the impact of asymmetry on chromatin remodeling and found that cancer-associated histone mutations can cause aberrant chromatin structure.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Bradley J. Lukasak, Robert E. Thompson, Michelle M. Mitchener, Vanessa J. Feng, John D. Bagert, Tom W. Muir
Summary: In this study, the SpyCatcher/SpyTag system was used to assemble desymmetrized nucleoprotein complexes. This method allows for the generation of nucleosomes with asymmetric modifications and facilitates the investigation of the effects of nucleosome asymmetry on chromatin remodeling processes and histone enzyme activity.
ACS CENTRAL SCIENCE
(2022)
Article
Microbiology
Negar Shahsavari, Boyuan Wang, Yu Imai, Miho Mori, Sangkeun Son, Libang Liang, Nils Boehringer, Sylvie Manuse, Michael F. Gates, Madeleine Morrissette, Rachel Corsetti, Josh L. Espinoza, Chris L. Dupont, Michael T. Laub, Kim Lewis
Summary: Drug-resistant Gram-negative bacteria pose a major challenge to antimicrobial treatments. This study focused on Photorhabdus, a gut symbiont of entomopathogenic nematodes, and discovered a novel antibiotic called ADG that selectively targets E. coli. ADG functions as a prodrug and inhibits transcription and cell division by interfering with GTP-dependent targets. This finding expands our understanding of prodrugs and provides potential solutions to antimicrobial resistance.
Article
Ecology
David Ding, Anna G. Green, Boyuan Wang, Thuy-Lan Vo Lite, Eli N. Weinstein, Debora S. Marks, Michael T. Laub
Summary: Neutral mutations in proteins can influence future mutational possibilities and functions. In a study of a bacterial toxin-antitoxin system, researchers identified enabling mutations that allow the toxin to tolerate mutations in the antitoxin. These enabling mutations expand mutational paths and have implications for protein design and evolutionary forecasting.
NATURE ECOLOGY & EVOLUTION
(2022)
Article
Multidisciplinary Sciences
Yang Liu, Xiaofeng Qi, Linda Donnelly, Nadia Elghobashi-Meinhardt, Tao Long, Rich W. Zhou, Yingyuan Sun, Boyuan Wang, Xiaochun Li
Summary: Wnt signalling plays a critical role in embryonic development and adult tissue homeostasis, and its dysregulation is associated with cancer. This study reveals the structure of human PORCN and provides insights into the mechanism of Wnt acylation, advancing the development of PORCN inhibitors for cancer treatment.
Article
Multidisciplinary Sciences
Aishan Zhao, Steven P. Bodine, Qian Xie, Boyuan Wang, Geeta Ram, Richard P. Novick, Tom W. Muir
Summary: This study reveals the involvement of membrane protease regulator of agr QS (MroQ) in the production of autoinducing peptide (AIP) in Staphylococcus aureus. It also uncovers the different roles of MroQ in different agr specificity groups, enhancing our understanding of the agr response and Staphylococcus aureus virulence.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Multidisciplinary
Giridhar Sekar, Adam J. Stevens, Anahita Z. Mostafavi, Pulikallu Sashi, Tom W. Muir, David Cowburn
Summary: Split intein-mediated protein trans-splicing (PTS) is a widely used method in chemical biology and biotechnology for traceless and specific protein ligation. The efficiency of PTS can be limited by external residues flanking the intein. In this study, a recently developed atypically split intein (Cat) was further modified to enhance its PTS activity in the presence of unfavorable N-extein residues. The mechanism behind the enhanced activity was explored using nuclear magnetic resonance spectroscopy and molecular dynamics simulations, highlighting the contribution of a conserved histidine residue. This enhanced extein tolerance of Cat* expands the applicability of atypically split inteins and reveals common principles of extein dependence.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Biochemistry & Molecular Biology
Michelle M. Mitchener, Tom W. Muir
Summary: Research over the past decade has revealed a new layer of epigenetic dysregulation, uncovering the association between somatic missense mutations in histones and human pathologies, especially cancer. While some of these mutations are believed to be key drivers of cancer, the effects of the majority of them on disease onset and progression are still unclear. Studies have shown that even at low dosage, histone mutants can corrupt chromatin states, providing insights into the intricate mechanisms of epigenetic control.
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)