Article
Biotechnology & Applied Microbiology
Marco Tulio Pardini Gontijo, Mateus Pereira Teles, Pedro Marcus Pereira Vidigal, Marcelo Brocchi
Summary: This study identifies new signal-anchor-release (SAR) Endolysin candidates and expands the arsenal of Endolysin candidates that might act against Gram-negative bacteria. These Endolysins are found in multiple protein families with SAR domains and are clustered into eight groups based on biochemical properties and domain presence/absence.
PROBIOTICS AND ANTIMICROBIAL PROTEINS
(2022)
Article
Infectious Diseases
Eric T. Sumrall, Marloes Hofstee, Daniel Arens, Christian Roehrig, Susanne Baertl, Dominic Gehweiler, Mathias Schmelcher, Martin J. Loessner, Stephan Zeiter, R. Geoff Richards, T. Fintan Moriarty
Summary: The study demonstrates that the addition of enzybiotics can enhance the treatment of severe MRSA ODRI by rapidly killing the bacteria and targeting biofilm formation.
Article
Microbiology
Fritz Eichenseher, Bjorn L. Herpers, Paul Badoux, Juan M. Leyva-Castillo, Raif S. Geha, Mathijs van der Zwart, James McKellar, Ferd Janssen, Bob de Rooij, Lavanja Selvakumar, Christian Roehrig, Johan Frieling, Mark Offerhaus, Martin J. Loessner, Mathias Schmelcher
Summary: In this study, two chimeric enzymes were constructed to selectively kill Staphylococcus aureus without affecting commensal skin bacteria. One of the enzymes showed higher activity in multiple in vitro assays. The formulated enzyme was effective at killing S. aureus on reconstituted human epidermis and significantly reduced bacterial numbers in a mouse model.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Feng Wang, Yao Xiao, Yao Lu, Zheng-Yu Deng, Xian-Yu Deng, Lian-Bing Lin
Summary: This study reports a lytic enzyme, P9ly, derived from a bacteriophage that can infect multidrug-resistant bacteria. P9ly can digest bacterial cell walls and exhibits bacteriolytic and bactericidal activity on different strains. The combined use of P9ly with ceftriaxone sodium improves the antibacterial effect.
FRONTIERS IN MICROBIOLOGY
(2022)
Review
Infectious Diseases
Marco Tulio Pardini Gontijo, Genesy Perez Jorge, Marcelo Brocchi
Summary: The heterologous expression of endolysin can be optimized to reduce toxicity and improve antimicrobial activity, while polyhistidine tags aid in purification and could enhance permeation when used with outer membrane permeabilizers.
Review
Biochemistry & Molecular Biology
Jose Ramos-Vivas, Maria Elexpuru-Zabaleta, Maria Luisa Samano, Alina Pascual Barrera, Tamara Y. Forbes-Hernandez, Francesca Giampieri, Maurizio Battino
Summary: Biopreservation methods such as protective bacterial cultures, antimicrobial products, plant-derived antibacterial compounds, bacteriophages, and their antibacterial enzymes are proposed to maintain the long shelf-life of food products. These alternatives to antimicrobials show great potential in reducing antibiotic use and combating antibiotic resistance in various sectors of the food industry.
Article
Biotechnology & Applied Microbiology
Yanhua Jiang, Dongqin Xu, Lianzhu Wang, Meng Qu, Fengling Li, Zhijun Tan, Lin Yao
Summary: The recombinant endolysin LysSP1 encoded by Salmonella Typhimurium lytic bacteriophage SLMP1 was obtained in this study, and EDTA was found to enhance its bactericidal activity. LysSP1 showed strong bactericidal activity against Salmonella Typhimurium, exhibited good stability, and demonstrated broad-spectrum bactericidal ability.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Article
Medicine, General & Internal
Roy H. Stevens, Hongming Zhang, Michal Kajsik, Rafal Ploski, Malgorzata Rydzanicz, Peter Sabaka, Stanislav Sutovsky
Summary: Chronic prostatitis (CP) is a common inflammatory condition of the prostate that affects 2%-10% of the world's male population. This study reports the successful use of a bacteriophage-derived muralytic enzyme to treat and resolve chronic bacterial prostatitis (CBP) in a 39 years-old patient.
FRONTIERS IN MEDICINE
(2023)
Article
Chemistry, Medicinal
Chanyoung Lee, Jinwoo Kim, Bokyung Son, Sangryeol Ryu
Summary: By swapping different domains of natural Staphylococcus endolysins, a novel chimeric endolysin ClyC was constructed, showing enhanced lytic activity against S. aureus, strong antibacterial effects in milk and blood, and effective eradication of biofilms of multidrug-resistant bacteria. The chimeric endolysin also demonstrated protection against MRSA in a mouse infection model, suggesting its potential as an antibacterial agent against multidrug-resistant S. aureus.
ACS INFECTIOUS DISEASES
(2021)
Article
Microbiology
Marzieh Asadi, Mortaza Taheri-Anganeh, Maryam Ranjbar, Seyyed Hossein Khatami, Amir Maleksabet, Zohreh Mostafavi-Pour, Younes Ghasemi, Abdolkhalegh Keshavarzi, Amir Savardashtaki
Summary: This study evaluated the antibacterial activity of a novel exolysin containing an SH3b domain against MRSA. The results showed that the chimeric exolysin LYZ2-SH3b had a more inhibitory effect on MRSA compared to LYZ2 and vancomycin.
Article
Food Science & Technology
Yeweon Choi, Eunsu Ha, Minsuk Kong, Sangryeol Ryu
Summary: Clostridium perfringens is a bacterium that causes diseases in humans and livestock. Antibiotic resistance is a growing concern, necessitating the search for alternative biocontrol agents. In this study, a C. perfringens-infecting bacteriophage and its endolysin were isolated and characterized. Through domain shuffling, a chimeric endolysin was generated with higher antimicrobial activity than the parental endolysin.
LWT-FOOD SCIENCE AND TECHNOLOGY
(2023)
Article
Microbiology
Marco Tulio Pardini Gontijo, Pedro Marcus Pereira Vidigal, Maryoris Elisa Soto Lopez, Marcelo Brocchi
Summary: The study focused on investigating the evolutionary markers of signal peptide-containing lysins to penetrate the outer membrane of Gram-negative bacteria, identifying potential candidates for the treatment of MDR bacteria.
RESEARCH IN MICROBIOLOGY
(2021)
Article
Microbiology
Chad W. Euler, Assaf Raz, Anaise Hernandez, Anna Serrano, Siyue Xu, Martin Andersson, Geng Zou, Yue Zhang, Vincent A. Fischetti, Jinquan Li
Summary: Klebsiella pneumoniae and Pseudomonas aeruginosa are leading causes of various infections, often resistant to multiple drugs. Discovering alternative antimicrobials, such as bacteriophage lysins, is crucial in combating these pathogens.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Chemistry, Medicinal
Adit B. Alreja, Sara B. Linden, Harrison R. Lee, Kinlin L. Chao, Osnat Herzberg, Daniel C. Nelson
Summary: The study reveals the molecular mechanisms of Cpl-1 and confirms the involvement of the C-terminal tail region in the formation of a dimer. Key residues that mediate Cpl-1 dimer formation are identified. These findings shed light on the mechanisms of Cpl-1 and related enzymes and can guide future engineering efforts for therapeutic development against S. pneumoniae.
ACS INFECTIOUS DISEASES
(2023)
Article
Biology
Salim Manoharadas, Mohammad Altaf, Abdulwahed Fahad Alrefaei, Naushad Ahmad, Shaik Althaf Hussain, Basel F. Al-Rayes
Summary: Researches have successfully designed an engineered antimicrobial protein to combat methicillin-resistant Staphylococcus aureus, showing strong activity. However, despite having a multimodular structure, the engineered protein failed to exhibit activity against a veterinary isolate of S. aureus.
Review
Biochemical Research Methods
Sara B. Linden, Adit B. Alreja, Daniel C. Nelson
Summary: The decline in new antibiotic candidates and the increase in antibiotic resistance have led to the development of alternative antimicrobials, such as bacteriophage-encoded endolysins. Current studies focus on the discovery, structure/function, engineering, immunogenicity, toxicity/safety, and efficacy of endolysins, with some already in human clinical trials. Streptococcal diseases primarily affect accessible mucous membranes, making them a promising target for protein therapeutics, such as targeted endolysin therapy.
CURRENT OPINION IN BIOTECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sebastian S. Broendum, Daniel E. Williams, Brooke K. Hayes, Felix Kraus, James Fodor, Ben E. Clifton, Anne Geert Volbeda, Jeroen D. C. Codee, Blake T. Riley, Nyssa Drinkwater, Kylie A. Farrow, Kirill Tsyganov, Ryan D. Heselpoth, Daniel C. Nelson, Colin J. Jackson, Ashley M. Buckle, Sheena McGowan
Summary: The study identified the polyrhamnose backbone of Group A streptococcal cell wall as the binding target of PlyC, and characterized the putative rhamnose binding groove of PlyC with critical residues. The interaction between PlyC and the cell wall may be a high avidity one rather than a high-affinity one, contributing to PlyC's remarkable lytic activity.
MOLECULAR MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Harley King, Sowmya Ajay Castro, Amol Arunrao Pohane, Cynthia M. Scholte, Vincent A. Fischetti, Natalia Korotkova, Daniel C. Nelson, Helge C. Dorfmueller
Summary: Endolysins are phage proteins that interact with bacterial cell walls through enzymatically active domains and cell wall binding domains, with the ability to lyse Gram-positive bacterial cells. They offer a potential alternative to traditional antibiotics, but research on the nature of CBDs and binding epitopes is still limited.
BIOCHEMICAL JOURNAL
(2021)
Article
Microbiology
Eric T. Sumrall, Stephan R. Schneider, Samy Boulos, Martin J. Loessner, Yang Shen
Summary: This study reveals that Listeria ivanovii interacts with phages, bacteria, and host cells, suggesting a common feature in the genus Listeria. Deletion of a unique glycosyltransferase in L ivanovii led to phage resistance and dysfunction of a major virulence factor, resulting in the strain's inability to invade host cells.
JOURNAL OF BACTERIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Andriy Kryshtafovych, John Moult, Reinhard Albrecht, Geoffrey A. Chang, Kinlin Chao, Alec Fraser, Julia Greenfield, Marcus D. Hartmann, Osnat Herzberg, Inokentijs Josts, Petr G. Leiman, Sara B. Linden, Andrei N. Lupas, Daniel C. Nelson, Steven D. Rees, Xiaoran Shang, Maria L. Sokolova, Henning Tidow
Summary: The paper discusses the successful application of computational models to assist experimental groups in solving protein structure targets, showing significant improvements in accuracy and the potential for increased synergy between computational and experimental approaches in future structure determination.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2021)
Article
Multidisciplinary Sciences
Kinlin L. Chao, Xiaoran Shang, Julia Greenfield, Sara B. Linden, Adit B. Alreja, Daniel C. Nelson, Osnat Herzberg
Summary: Four tailspike proteins enable infection of multiple bacterial hosts by the Escherichia coli O157:H7 bacteriophage CBA120. The crystal structure of one of these proteins, TSP4-N-335, reveals its trimeric nature and its role in anchoring the complex to the tail baseplate. Further analyses show that different regions of TSP4 are responsible for binding to other proteins. A 3-dimensional model of the bacteriophage CBA120 TSP complex has been developed based on these findings.
SCIENTIFIC REPORTS
(2022)
Article
Immunology
Meghna Thakur, Sandhya Bista, Shelby D. Foor, Shraboni Dutta, Xiuli Yang, Michael Ronzetti, Vipin S. Rana, Chrysoula Kitsou, Sara B. Linden, Amanda S. Altieri, Bolormaa Baljinnyam, Daniel C. Nelson, Anton Simeonov, Utpal Pal
Summary: The protein BB0323 of Borrelia burgdorferi undergoes a proteolytic maturation event mediated by the protease BbHtrA, which cleaves BB0323 between specific amino acids. Mutations at these cleavage sites affect the interaction between BB0323 and BbHtrA, leading to impaired infection ability of Borrelia burgdorferi.
INFECTION AND IMMUNITY
(2022)
Article
Microbiology
Ryan D. Heselpoth, Chad W. Euler, Vincent A. Fischetti
Summary: This study evaluates the antibacterial properties of a modified cationic peptide, PaP1, derived from the broad-acting lysin PlyPa01. PaP1 exhibits potent in vitro bactericidal activity against high priority Gram-positive and Gram-negative pathogens, including antibiotic-resistant strains. The peptide is effective against both planktonic and biofilm-state bacteria, and it is non-toxic to human cells. In addition, PaP1 enhances the potency of topical antibiotics in treating chronic wound infections in a murine model.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Infectious Diseases
Marek Adam Harhala, Katarzyna Gembara, Daniel C. Nelson, Paulina Miernikiewicz, Krystyna Dabrowska
Summary: This study evaluated the immunogenicity of PlyC, an antibacterial enzyme, in humans and mice. PlyC induced efficient IgG production in mice and interacted specifically with the PlyCA subunit. Approximately 10% of the human population showed immune reactivity to the PlyCB subunit, but no hypersensitivity reactions were observed.
Article
Biochemistry & Molecular Biology
Di Wu, Jiangtao Zhou, Yang Shen, Cristina Lupo, Qiyao Sun, Tonghui Jin, Shana J. Sturla, Hongshan Liang, Raffaele Mezzenga
Summary: A novel soft hydrogel scaffold was successfully constructed by incorporating polyphenol modules with lysozyme amyloid fibrils. This hydrogel not only showed good biocompatibility, but also exhibited superior cell adhesion efficiency, promoting cell proliferation and spreading. This study is significant for the design and development of future biomaterials.
Article
Pharmacology & Pharmacy
Yuncheng Wang, Dipesh Khanal, Adit B. Alreja, Hang Yang, Rachel Y. K. Chang, Waiting Tai, Mengyu Li, Daniel C. Nelson, Warwick J. Britton, Hak-Kim Chan
Summary: This study investigated the feasibility of producing inhalable powders of endolysins Cpl-1 and ClyJ-3 using spray drying method with excipients. The results showed that ClyJ-3 lost its bioactivity before the drying process, while Cpl-1 maintained its bioactivity in the spray-dried powders. Cpl-1 formulations with leucine and either lactose or trehalose exhibited promising physico-chemical properties and aerosol performances. These findings suggest that endolysin Cpl-1 can be formulated as spray dry powders for potential treatment of pulmonary infections.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Chemistry, Multidisciplinary
Hao Ye, Kaiyuan Wang, Jian Zhao, Qi Lu, Menglin Wang, Bingjun Sun, Yang Shen, Hongchen Liu, Salvador Pane, Xiang-Zhong Chen, Zhonggui He, Jin Sun
Summary: The use of Golgi apparatus-Pd-l1 (-/-) exosome hybrid membrane coated nanoparticles (GENPs) can significantly reduce the secretion of PD-L1, leading to reduced tumor relapse rates. GENPs accumulate in tumors and disrupt PD-L1 production and exosome release through induction of intracellular events. Furthermore, they can mimic exosomes to activate T cells and promote systemic immune responses.
Article
Chemistry, Medicinal
Adit B. Alreja, Sara B. Linden, Harrison R. Lee, Kinlin L. Chao, Osnat Herzberg, Daniel C. Nelson
Summary: The study reveals the molecular mechanisms of Cpl-1 and confirms the involvement of the C-terminal tail region in the formation of a dimer. Key residues that mediate Cpl-1 dimer formation are identified. These findings shed light on the mechanisms of Cpl-1 and related enzymes and can guide future engineering efforts for therapeutic development against S. pneumoniae.
ACS INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Chih-Hung Wu, Jeanine Rismondo, Rhodri M. L. Morgan, Yang Shen, Martin J. Loessner, Gerald Larrouy-Maumus, Paul S. Freemont, Angelika Grundling
Summary: Research showed that Bacillus subtilis has multiple UDP-glucose synthesizing enzymes, among which YngB is a newly discovered enzyme with UGPase activity. YngB can reintroduce glucose residues on wall teichoic acid and produce glucolipids in a B. subtilis gtaB mutant.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Yang Shen, Ioanna Kalograiaki, Alessio Prunotto, Matthew Dunne, Samy Boulos, Nicholas M. I. Taylor, Eric T. Sumrall, Marcel R. Eugster, Rebecca Martin, Alicia Julian-Rodero, Benjamin Gerber, Petr G. Leiman, Margarita Menendez, Matteo Dal Peraro, Francisco Javier Canada, Martin J. Loessner
Summary: This study reveals the molecular interaction mechanism between the Listeria phage endolysin domain CBD500 and its cell wall teichoic acid (WTA) ligands, showing that 3' O-acetylated GlcNAc residues are the key epitope recognized by CBD. The findings provide insights into a previously unknown recognition mechanism that phage endolysin specifically targets WTA, suggesting a flexible model for regulating endolysin specificity.