Article
Biology
Paul Lambey, Omolade Otun, Xiaojing Cong, Francois Hoh, Luc Brunel, Pascal Verdie, Claire M. Grison, Fanny Peysson, Sylvain Jeannot, Thierry Durroux, Cherine Bechara, Sebastien Granier, Cedric Leyrat
Summary: The study characterized the interaction of LukE with chemokine receptors ACKR1, CCR2, and CCR5, revealing the location of receptor sulfotyrosine binding sites in the toxins. This work provides new insights into chemokine receptor recognition by leukotoxins and suggests that the conserved sulfotyrosine binding pocket could be a target for future drug development.
Article
Microbiology
Isabel Guthridge, Simon Smith, Matthew Law, Enzo Binotto, Josh Hanson
Summary: Lincosamides, particularly when used as a predominant therapy, show potential efficacy in the treatment of MRSA bacteremia, especially in young, clinically stable patients with few comorbidities. Patients receiving lincosamide-predominant therapy had lower in-hospital mortality and a lower incidence of renal complications compared to those receiving an alternative regimen. Prospective studies are needed to further define the optimal role of lincosamides in the treatment of MRSA bacteremia.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Bulat Fatkhullin, Alexander Golubev, Natalia Garaeva, Shamil Validov, Azat Gabdulkhakov, Marat Yusupov
Summary: The conserved protein RsfS plays a role in ribosome shutdown and cell survival during starvation, and is involved in the biogenesis of the large ribosomal subunit. In this study, the contribution of specific amino acid side chains at the interface between RsfS and uL14 in Staphylococcus aureus was investigated. The results suggest that the Y98 amino acid on RsfS surface may be a potential target for drug development and treatment of S. aureus infections.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Thu Giang Nguyen, Christina Ritter, Eva Kummer
Summary: Mitochondria contain their own genetic information and translation system. Researchers have discovered that GTPBP10 plays a role in the folding of mitochondrial ribosomal RNA during the biogenesis process, which is related to bacterial ribosome biogenesis. Unlike bacteria, mitochondria require two biogenesis factors. This study reveals the process of maturation in the human mitoribosome and the interplay between GTPBP10 and GTPBP7.
NATURE COMMUNICATIONS
(2023)
Article
Microbiology
Anna Liponska, Mee-Ngan F. Yap
Summary: Bacterial and eukaryotic hibernation factors physically block the decoding center of ribosomes to prevent translation, with Staphylococcus aureus lacking HPF showing susceptibility to ribosome degradation due to RNase R activity. HPF binding inhibits ribosome degradation by RNase R, highlighting a direct protective role of HPF in ribosome stability and the versatility of RNase R in RNA processing and decay.
Article
Infectious Diseases
Felipe Fernandez-Cuenca, Inmaculada Lopez-Hernandez, Emilia Cercenado, Carmen Conejo, Nuria Tormo, Concha Gimeno, Alvaro Pascual
Summary: The study evaluated the proficiency of microbiology laboratories in Spain in antimicrobial susceptibility testing of Staphylococcus spp. It found discrepancies and errors, particularly with gradient diffusion, EUCAST breakpoints, and certain antimicrobials, highlighting the need for improvement.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Ting Yu, Junyi Jiang, Qianxi Yu, Xin Li, Fuxing Zeng
Summary: Magnesium ions are abundant and crucial in the ribosome, and a decrease in its concentration leads to ribosome dissociation and structural distortion. This study focused on the structural distortion of the 30S subunit under different magnesium concentrations. The decoding center and h17 were found to be significantly distorted, and the requirement for magnesium ions suggests that these conformational changes may be shared across all domains of life due to magnesium deficiency.
Article
Chemistry, Multidisciplinary
Adeline Espinasse, Manibarsha Goswami, Junshu Yang, Onanong Vorasin, Yinduo Ji, Erin E. Carlson
Summary: The emergence of drug-resistant bacteria has led to the need for novel approaches and targets to combat this challenge. Bacterial two-component systems (TCSs) are important in bacterial adaptive responses and are linked to antibiotic resistance and virulence. A study developed maleimide-based compounds and evaluated them against a model histidine kinase, resulting in the identification of a molecule that decreased the lesion size caused by methicillin-resistant S. aureus skin infection by 65% in a murine model.
Article
Infectious Diseases
Bingjie Wang, Jingjing Duan, Ye Jin, Qing Zhan, Yanlei Xu, Huilin Zhao, Xinyi Wang, Lulin Rao, Yinjuan Guo, Fangyou Yu
Summary: The study identified the conserved role of mraZ in Staphylococcus aureus, highlighting its essential contribution to virulence and immune evasion. MraZ was found to regulate various virulence genes and may serve as a potential target for anti-virulence therapy.
INFECTION AND DRUG RESISTANCE
(2021)
Article
Biochemistry & Molecular Biology
Margarita Belinite, Iskander Khusainov, Heddy Soufari, Stefano Marzi, Pascale Romby, Marat Yusupov, Yaser Hashem
Summary: Cryo-electron microscopy is now a preferred method for studying protein synthesis through ribosome machinery. To achieve high-resolution structures, optimization of ribosome purification in a species-dependent manner is necessary. This study demonstrates the importance of spermidine in stabilizing the 30S ribosomal subunit by preserving favorable conformation of helix 44.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Matthias Thoms, Benjamin Lau, Jingdong Cheng, Lisa Fromm, Timo Denk, Nikola Kellner, Dirk Flemming, Paulina Fischer, Laurent Falquet, Otto Berninghausen, Roland Beckmann, Ed Hurt
Summary: The study isolated and described the conserved rixosome from Chaetomium thermophilum, which consists of two sub-modules, Rix1-Ipi3-Ipi1 and Las1-Grc3 complex. The Rix1 complex plays a key role in pre-60S particles by inserting between the 5S rRNA tip and L1-stalk, facilitating the rotation of immature 5S RNP. The other sub-module with Las1 endonuclease and Grc3 polynucleotide-kinase cleaves and phosphorylates the nearby ITS2 pre-rRNA at the pre-60S foot. Inward movement of the L1 stalk permits the Nop53 N-terminus with AIM motif to participate in completing ITS2 removal.
Article
Pharmacology & Pharmacy
Ekaterina Nefedova, Nikolay Shkil, Roberto Luna Vazquez-Gomez, Diana Garibo, Alexey Pestryakov, Nina Bogdanchikova
Summary: This study investigates the effect of silver nanoparticles on the drug resistance of Staphylococcus aureus in the treatment of mastitis. The results show that treatment with silver nanoparticles can enhance the susceptibility of S. aureus to antibiotics and reduce the duration of treatment.
Review
Immunology
Emilio G. Vozza, Michelle E. Mulcahy, Rachel M. McLoughlin
Summary: The success of Staphylococcus aureus as a human commensal and opportunistic pathogen lies in its ability to adapt to various niches within the host. Evading the host's innate immune response, S. aureus can parasitize phagocytes and manipulate the autophagy pathway to create an intracellular survival niche. Neutrophils play a critical role in S. aureus infection, with the bacterium surviving and potentially impacting host signaling pathways for its own benefit.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Gopinatha Krishnappa, Mitali Mandal, Saranya Ganesan, Sudhagar Babu, Sivaraman Padavattan, Veena Kumari Haradara Bahubali, Balasundaram Padmanabhan
Summary: Methicillin-resistant Staphylococcus aureus (MRSA) is a life-threatening human infection. Bacteriophage-encoded endolysins, such as PlyGRCS, show promise in combating bacterial infections by degrading cell walls. The crystal structure and biochemical results of PlyGRCS provide insight into its bacteriolytic activity against S. aureus and its interaction with the cold-shock protein C (CspC), which may downregulate CspC's function during bacterial infection.
Review
Biochemistry & Molecular Biology
Mario S. Valdes-Tresanco, Andrea Molina-Zapata, Alain Gonzalez Pose, Ernesto Moreno
Summary: Nanobodies, a unique class of antibody fragments, have numerous advantages and great potential in diagnostics and therapeutics. Recent advances in synthetic nanobody libraries have shown important advantages over animal-based approaches.
Article
Biochemistry & Molecular Biology
Raphael Benhamou, Shruti Choudhary, Elizabeth Lekah, Yuquan Tong, Matthew D. Disney
Summary: Studies have shown that selective molecular recognition of RNA targets by small molecules in cells is possible, with one strategy being the simultaneous binding of two or more sites within RNA with a single molecule. By informatically mining human miRNA precursors, targets amenable to small molecule targeting can be identified, with oncogenic miRNA-27a being a lead molecule that can inhibit miRNA processing in cancer cells. This demonstrates that a synergistic approach involving bioinformatics and experimental methods can define suitable targets for small molecule targeting.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Medicinal
Rebecca Elias, Pallabita Basu, Micha Fridman
Summary: This study evaluated the activity of drug hybrids combining azole antifungal drugs with COX inhibitors. Hybrids derived from ibuprofen and flurbiprofen showed stronger inhibition against Candida species compared to fluconazole and comparable to voriconazole. The hybrids with an S-configured azole pharmacophore exhibited higher potency. These hybrids exert their effects via a dual mode of action and are active against mutants lacking the target of azole drugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Tanaya Bose, Gil Fridkin, Chen Davidovich, Miri Krupkin, Nikita Dinger, Alla H. Falkovich, Yoav Peleg, Ilana Agmon, Anat Bashan, Ada Yonath
Summary: This study demonstrates that several protoribosome constructs have the ability to mediate peptide-bond formation, providing strong evidence for the hypothesis on the origin of life and the construction of ribosomes. These findings suggest that the protoribosome may serve as the missing link between the RNA dominated world and the contemporary nucleic acids/proteins life.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Raphael I. Benhamou, Blessy M. Suresh, Yuquan Tong, Wesley G. Cochran, Valerie Cavett, Simon Vezina-Dawod, Daniel Abegg, Jessica L. Childs-Disney, Alexander Adibekian, Brian M. Paegel, Matthew D. Disney
Summary: Nature evolves molecular interaction networks through persistent perturbation and selection, presenting a stark contrast to the current drug discovery process. By recapitulating nature's search paradigm in a screen of a DNA-encoded library against a library of RNA structures, high-affinity and selective ligand-RNA interactions can be identified and their cellular engagements predicted.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Genetics & Heredity
Ana Cristina Colabardini, Fang Wang, Zhiqiang Dong, Lakhansing Pardeshi, Marina Campos Rocha, Jonas Henrique Costa, Thaila Fernanda dos Reis, Alec Brown, Qais Z. Jaber, Micha Fridman, Taicia Fill, Antonis Rokas, Iran Malavazi, Koon Ho Wong, Gustavo Henrique Goldman
Summary: This study investigates the molecular mechanisms underlying heterogeneity in the response to the antifungal drug caspofungin in different Aspergillus fumigatus strains. The study found that a core transcriptional response involving genes related to cell wall remodeling, mitochondrial function, transmembrane transport, and metabolism, as well as a variable response related to secondary metabolite biosynthesis and iron homeostasis, contribute to the heterogeneity in response. Furthermore, the study highlights the role of the transcription factor CrzA in modulating the expression of genes related to CSP tolerance and SM production, impacting the CPE response in different strains.
Article
Biochemistry & Molecular Biology
Qais Z. Jaber, Dana Logviniuk, Adi Yona, Micha Fridman
Summary: Echinocandin antifungal drugs have broad-spectrum activities and excellent safety profiles by inhibiting the formation of major polysaccharides in the fungal cell wall. Fluorescent echinocandins, including caspofungin, anidulafungin, and rezafungin, maintain the same spectrum of activities as their non-fluorescent counterparts, with each drug probe showing a unique subcellular distribution pattern in live Candida yeast cells.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Dana Logviniuk, Qais Z. Jaber, Roman Dobrovetsky, Noga Kozer, Ewa Ksiezopolska, Toni Gabaldon, Shmuel Carmeli, Micha Fridman
Summary: Each year, fungal infections cause millions of deaths and affect billions of people worldwide. Echinocandins, a new class of antifungal drugs, inhibit the synthesis of fungal cell wall components. This study demonstrates the effectiveness of a chemical modification strategy to restore the efficacy of echinocandins against drug-resistant fungal pathogens.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Microbiology
Giuseppe Cimicata, Gil Fridkin, Tanaya Bose, Zohar Eyal, Yehuda Halfon, Elinor Breiner-Goldstein, Tara Fox, Ella Zimmerman, Anat Bashan, Natalia de Val, Alexander Wlodawer, Ada Yonath
Summary: This study used cryo-EM techniques to image ribosomes from Staphylococcus aureus and identified a previously unobserved conformation. The findings shed light on the mechanism and significance of the helix 68 in the protein synthesis process.
Article
Chemistry, Medicinal
Tristan Wegner, Rebecca Elias, Lena Roling, Nikita Raj, Volker Gerke, Micha Fridman, Frank Glorius
Summary: This study reports a library of novel cationic amphiphiles that exhibit tunable antifungal activity and low hemolytic activity. The use of an ergosterol-derived backbone enhances antifungal activity while increasing selectivity, which holds great potential for the development of improved amphiphilic fungicides.
ACS INFECTIOUS DISEASES
(2022)
Article
Chemistry, Multidisciplinary
Yeseul Park, Zohar Eyal, Peter Pekker, Daniel M. Chevrier, Christopher T. Lefevre, Pascal Arnoux, Jean Armengaud, Caroline L. Monteil, Assaf Gal, Mihaly Posfai, Damien Faivre
Summary: This study reports the periplasmic biomineralization of copper sulfide nanoparticles produced by the magnetotactic bacterium Desulfamplus magnetovallimortis strain BW-1. It reveals previously unknown possibilities for intracellular biomineralization and holds promise for biological metal recovery.
Review
Chemistry, Multidisciplinary
Micha Fridman, Kaori Sakurai
Summary: The increasing number of fungal infections caused by drug-resistant pathogens highlights the threat they pose to animal and human health, as well as global food security. The limited understanding of the mechanisms of antifungal agents makes it difficult to develop more effective therapies. However, the use of chemical biology approaches has provided promising concepts for the design of antifungal agents, as they have helped uncover details about their activities, detect resistance, and characterize the interactions between these agents and their targets.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Caroline E. Wagner, Miri Krupkin, Kathryn B. Smith-Dupont, Chloe M. Wu, Nicole A. Bustos, Jacob Witten, Katharina Ribbeck
Summary: Simulating native mucus with reconstituted mucin gels or commercially available polymers provides experimental advantages, but systematic comparisons are rarely reported. In this study, we compared the properties of mucus from different sources, reconstituted mucin gels, and commonly used polymers. Our results show that mucin gels replicate the mechanical response and transport behavior of native mucus, while commercially available mucins and carboxymethylcellulose exhibit significant differences. The selection of a mucus model system based on the length scale relevant to the scientific investigation or disease application is crucial.
Article
Chemistry, Multidisciplinary
Zohar Eyal, Rachael Deis, Neta Varsano, Nili Dezorella, Katya Rechav, Lothar Houben, Dvir Gur
Summary: Controlling the morphology of crystalline materials is challenging, but organisms are capable of forming crystals with distinct morphologies. Using cryo-electron tomography, researchers discovered that guanine crystals form through templated nucleation and merging of thin leaflets on preassembled scaffolds. This finding sheds light on the biological regulation of crystal morphogenesis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Emanuel M. Avrahami, Zohar Eyal, Neta Varsano, Ievgeniia Zagoriy, Julia Mahamid, Assaf Gal
Summary: This study investigates the growth process of coccolith crystals using advanced electron microscopy techniques. It reveals that the crystals grow alternately between space filling and skeletonized growth modes, with the final morphology influenced by growth arrest. The findings shed light on the delicate regulation of coccolith crystal morphology.
ADVANCED MATERIALS
(2023)
Article
Chemistry, Medicinal
Tristan Wegner, Rebecca Elias, Lena Roling, Nikita Raj, Volker Gerke, Micha Fridman, Frank Glorius
Summary: A library of cationic, steroid-based imidazolium amphiphiles with tunable antifungal activity was reported. The adoption of an ergosterol-derived backbone increased the antifungal activity and selectivity, offering a promising platform for the development of improved amphiphilic fungicides.
ACS INFECTIOUS DISEASES
(2022)
