Article
Engineering, Biomedical
Leman Buzoglu Kurnaz, Swagatam Barman, Xiaoming Yang, Claire Fisher, F. Wayne Outten, Prakash Nagarkatti, Mitzi Nagarkatti, Chuanbing Tang
Summary: Inspired by the facial amphiphilic nature and antimicrobial efficacy of antimicrobial peptides, this study developed a new class of facial amphiphilic bicyclic naphthoic acid derivatives that were attached to poly(glycidyl methacrylate). These polymers exhibited potent antibacterial activity against multi-drug resistant gram-negative pathogens and showed low hemolysis and high antimicrobial selectivity. They were also effective in eradicating biofilms and killing dormant cells, suggesting a mechanism of action through membrane disruption. Overall, these facial amphiphiles have the potential to address antimicrobial resistance in both planktonic and biofilm-related infections.
Article
Materials Science, Multidisciplinary
Xiao Zhu, Weilong Tang, Xinyi Cheng, Huihui Wang, Ting Sang, Zhou Ye
Summary: Antimicrobial peptide (AMP) coatings are a promising alternative to conventional antibiotics for preventing infections associated with medical devices and implants. This study found that self-assembled AMPs were more effective in killing Gram-positive Staphylococcus aureus than free AMPs, suggesting their potential to be used in the design of more stable and effective antimicrobial coatings.
Article
Engineering, Biomedical
Zhiyong Chen, Cailing Zhou, Yangfan Xu, Kang Wen, Junfeng Song, Silei Bai, Chenxuan Wu, Wei Huang, Qingyun Cai, Kai Zhou, Hui Wang, Yingjie Wang, Xinxin Feng, Yugang Bai
Summary: The increasing number of infections caused by multi-drug resistance (MDR) bacteria indicates a new global challenge. Antimicrobial peptides (AMPs) and AMP mimics are emerging as effective agents due to their low resistance rate and effectiveness against MDR strains. A novel oligomer with an alternatingly amphiphilic structure and affinity for bacterial DNA demonstrates high therapeutic index and in vivo activity, showing potential as a resistance-resistant and selective antimicrobial agent.
Article
Engineering, Biomedical
Xianhui Chen, Cailing Zhou, Jianxue Wang, Tong Wu, E. Lei, Yi Wang, Guopu Huang, Yue Yu, Qingyun Cai, Huangsheng Pu, Xinxin Feng, Yugang Bai
Summary: Antimicrobial peptidomimetics (AMPMs) are potential powerful weapons against antibiotic resistance. However, their membrane disruption mechanism brings concerns about resistance-resistant nature, nonspecific binding and disruption towards eukaryotic cell membranes. Hemolytic activity is the primary concern in clinical applications. In this study, an AMPM library was prepared and screened to identify the best-performing hit, PT-b1. A strategy was devised to improve PT-b1's hemocompatibility using a charge-free, FDA-approved amphiphilic polymer, Pluronic F-127 (PF127). The in vivo effectiveness of the antimicrobial hydrogel system was demonstrated using a mice wound infection model.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Chemistry, Multidisciplinary
Changxuan Shao, Yongjie Zhu, Qiao Jian, Zhenheng Lai, Peng Tan, Guoyu Li, Anshan Shan
Summary: Novel antimicrobial peptides have been developed as potential antibiotic substitutes, with a focus on a progressive beta-hairpin solution to reveal the balance between function and toxicity of structural moieties. Lead amphiphiles have shown promising antimicrobial efficacy and potential inflammation-limiting capabilities without observed toxicity, providing renewed innovation in beta-sheet peptide-based antimicrobial biomaterials.
Article
Engineering, Biomedical
Nhan D. T. Tram, Vanitha Selvarajan, Alister Boags, Devika Mukherjee, Jan K. Marzinek, Bernadette Cheng, Zi-Chen Jiang, Pascal Goh, Jun-Jie Koh, Jeanette W. P. Teo, Peter J. Bond, Pui Lai Rachel Ee
Summary: By examining the significance of the turn region of beta-hairpin peptides, valuable knowledge was presented for the design of novel antimicrobial peptides. The de novo designed synthetic peptides displayed selective activity against Gram-negative bacteria and potent activity against clinically relevant antibiotic-resistant strains. Our peptides showed robust bactericidal activity in challenging conditions and were non-cytotoxic against human cells.
ACTA BIOMATERIALIA
(2021)
Article
Pharmacology & Pharmacy
Pankhuri Narula, Sankar Kiruthika, Shruti Chowdhari, Perumal Vivekanandan, Archana Chugh
Summary: We investigate the role of Tachyplesin (Tpl), a marine antimicrobial cell-penetrating peptide, as an anti-HBV agent. Our findings demonstrate the internalization of FITC-Tpl in both Huh7 and HepG2 cell lines. Tpl inhibits the expression of HBV proteins and reduces levels of HBV pre-core RNA and HBV pregenomic RNA, suggesting its potential as an effective therapeutic peptide against HBV.
Article
Biochemistry & Molecular Biology
Xue Wang, Shuxian Li, Mengze Du, Ning Liu, Qiang Shan, Yunjing Zou, Jiufeng Wang, Yaohong Zhu
Summary: In this study, recombinant Zophobas atratus (Z. atratus) defensin was successfully expressed for the first time, and 5 analogues derived from Z. atratus defensin were designed to enhance the antimicrobial activity. Among these analogues, Z-d14CFR exhibited a broad-spectrum antimicrobial activity with minimal hemolysis and cytotoxicity. Mechanistic studies revealed that Z-d14CFR exerted its antimicrobial effect by inhibiting biofilm formation, disrupting bacterial membrane integrity, and inducing cellular contents release. Moreover, Z-d14CFR showed significant therapeutic efficacy in a murine model of multidrug-resistant Escherichia coli (E. coli) infection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Jingru Shi, Chen Chen, Dejuan Wang, Ziwen Tong, Zhiqiang Wang, Yuan Liu
Summary: The study demonstrated that peptide WW307 displayed potent antibacterial activity against MDR bacteria, especially MRSA and Gram-negative pathogens carrying bla(NDM-5), mcr-1 or tet(X4). Additionally, WW307 showed great biofilm inhibition and eradication activity. Safety and stability experiments also indicated that WW307 had potential as a candidate for combating MDR pathogens.
Article
Multidisciplinary Sciences
Christin Pohl, Gregory Effantin, Eaazhisai Kandiah, Sebastian Meier, Guanghong Zeng, Werner Streicher, Dorotea Raventos Segura, Per H. Mygind, Dorthe Sandvang, Line Anker Nielsen, Gunther H. J. Peters, Guy Schoehn, Christoph Mueller-Dieckmann, Allan Noergaard, Pernille Harris
Summary: This study reports the cryo-EM structure of a triple-mutant of the antimicrobial peptide plectasin, which assembles into helical non-amyloid fibrils. The fibril formation is reversible and pH- and concentration-dependent. This finding reveals that alpha/beta proteins can naturally assemble into fibrils.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Loan Huynh, Jeanette Velasquez, Roel Rabara, Supratim Basu, Hau B. Nguyen, Goutam Gupta
Summary: The study found that terminal carboxyl capping enhances the membrane insertion and antibacterial activity of AMP P1, and bacterial strains with evolved resistance can become susceptible to variants of P1 with either backbone capping or lysine-to-arginine substitutions. Cocktail combinations of closely related AMPs may be useful in overcoming evolved resistance.
COMPUTATIONAL BIOLOGY AND CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Federica Armas, Adriana Di Stasi, Mario Mardirossian, Antonello A. Romani, Monica Benincasa, Marco Scocchi
Summary: The study tested two different lipidated forms of Bac7(1-16) aimed at extending its activity against bacterial species lacking SbmA. Both lipidated forms showed activity against Gram-positive and Gram-negative bacteria at low micromolar MIC values. These results suggest that C-terminal lipidation alters the function and mode of action of a short proline-rich peptide, providing insights into the design of broad-spectrum antibacterial agents.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Aaron P. Decker, Abraham F. Mechesso, Guangshun Wang
Summary: Unlike the alpha-helical and beta-sheet antimicrobial peptides (AMPs), amino acid-rich AMPs have limited knowledge. This article conducted a systematic study on rich AMPs (>25%) from different life kingdoms using the Antimicrobial Peptide Database (APD) and program R. Of the 3425 peptides analyzed, 724 rich AMPs were identified. The distribution of rich AMPs differs among animals, bacteria, and plants. Certain amino acids are frequently observed in rich AMPs, while others are occasionally observed or not yet found. These findings can guide peptide design and rich AMPs show promise as future antibiotics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Sung-Pang Chen, Eric H-L Chen, Sheng-Yung Yang, Pin-Shin Kuo, Hau-Ming Jan, Tsai-Chen Yang, Ming-Yen Hsieh, Kung-Ta Lee, Chun-Hung Lin, Rita P-Y Chen
Summary: Searching for new antimicrobials is vital to combat multidrug-resistant bacteria and fungi. Antimicrobial peptides offer new hope, but stability and selectivity are crucial considerations. By studying the peptide pepD2, it was found that different residues and modifications can impact antimicrobial activity, stability, and toxicity.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Microbiology
Min Seok Kwun, Dong Gun Lee
Summary: The study investigated the antibacterial mode of action of tachyplesin I against Escherichia coli, revealing that it induces apoptosis-like death in E. coli through mechanisms such as increased reactive oxygen species, imbalance in intracellular ion concentration, and DNA damage. This finding suggests the potential of tachyplesin I as a candidate for regulating bacterial infection.
JOURNAL OF BASIC MICROBIOLOGY
(2021)
Editorial Material
Chemistry, Medicinal
Mark Blaskovich
ACS INFECTIOUS DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Jennifer R. Baker, Peter J. Cossar, Mark A. T. Blaskovich, Alysha G. Elliott, Johannes Zuegg, Matthew A. Cooper, Peter J. Lewis, Adam McCluskey
Summary: Five focused compound libraries were synthesized and screened for antibiotic and anti-fungal activity. Modifications of the terminal aromatic moiety were explored, resulting in the discovery of compounds with improved activity.
Article
Computer Science, Information Systems
Hardik A. Jain, Vinti Agarwal, Chaarvi Bansal, Anupama Kumar, Faheem FaheemFaheem, Muzaffar-Ur-Rehman Mohammed, Sankaranarayanan Murugesan, Moana M. Simpson, Avinash V. Karpe, Rohitash Chandra, Christopher A. MacRaild, Ian K. Styles, Amanda L. Peterson, Matthew A. Cooper, Carl M. J. Kirkpatrick, Rohan M. Shah, Enzo A. Palombo, Natalie L. Trevaskis, Darren J. Creek, Seshadri S. Vasan
Summary: Repurposing approved drugs is an excellent strategy to quickly obtain safe and effective COVID-19 treatments. To address this, the CoviRx.org platform provides a user-friendly interface for analyzing and filtering large quantities of data, while encouraging users to submit their findings. This will help combat the pandemic and expand to other diseases.
Article
Engineering, Chemical
Sadaf Aiman Khan, Marut Jain, Kamal Kishore Pant, Zyta Maria Ziora, Mark A. T. Blaskovich
Summary: Methylparaben (MeP) is a serious water pollutant in cosmetic industry effluents, but a hybrid catalyst of silver nanoparticles on reduced graphene oxide (rGO/AgNPs) fabricated using a green reducing agent showed significantly enhanced photocatalytic degradation efficiency of MeP. The conditions influencing the degradation kinetics were comprehensively studied using response surface methodology. The nanocomposite exhibited high stability and potential for multiple cycles of use, providing new insights into the development of low-cost photocatalysts for cosmetic wastewater treatment.
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Ramar Perumal Samy, Stephen P. P. Mackessy, Alagarmalai Jeyasankar, Mano Ranjana Ponraj, Octavio Luiz Franco, Matthew A. A. Cooper, Matheswaran Kandasamy, Tapan Kumar Mohanta, Jebasingh Bhagavathsingh, Sakthivel Vaiyapuri
Summary: PaTx-II, an active component from the venom of the Mulga Snake, showed potent antimicrobial activity and promoted wound healing.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biotechnology & Applied Microbiology
Mark S. Butler, Ian R. Henderson, Robert J. Capon, Mark A. T. Blaskovich
Summary: The global need for new antibacterial drugs to combat drug-resistant bacterial infections is receiving significant attention, leading to numerous funding, policy, and legislative initiatives to support antibacterial research and development. This review assesses the impact of these programs by analyzing the clinical development of various types of antibacterial drugs and the number of drug approvals in recent years. The findings show an increasing number of early-stage candidates and a presence of novel antibacterial compounds, particularly targeting Gram-negative bacteria.
JOURNAL OF ANTIBIOTICS
(2023)
Review
Chemistry, Multidisciplinary
Angelo Frei, Anthony D. D. Verderosa, Alysha G. G. Elliott, Johannes Zuegg, Mark A. T. Blaskovich
Summary: Metal ions have antimicrobial activity and are considered as potential new antibiotics. Metal complexes can also be used for antimicrobial photodynamic therapy and radionuclide diagnosis of bacterial infections.
NATURE REVIEWS CHEMISTRY
(2023)
Article
Biology
Bing Zhang, Wanida Phetsang, M. Rhia L. Stone, Sanjaya Kc, Mark S. S. Butler, Matthew A. A. Cooper, Alysha G. G. Elliott, Urszula Lapinska, Margaritis Voliotis, Krasimira Tsaneva-Atanasova, Stefano Pagliara, Mark A. T. Blaskovich
Summary: Antimicrobial resistance is a critical concern for human health, and this study presents the development of vancomycin fluorescent probes that can be used for detecting and visualizing Gram-positive bacteria as well as for measuring outer membrane permeabilization in Gram-negative bacteria. The probes were synthesized by modifying vancomycin with an azide substituent, enabling it to undergo copper-catalyzed azide-alkyne cycloaddition reactions. The probes exhibited similar antibacterial profiles to the parent vancomycin antibiotic and were versatile tools for various detection and imaging techniques.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Annick van Niekerk, M. Cassiem Joseph, Angela Kavanagh, Hue Dinh, Andrew J. Swarts, Selwyn F. Mapolie, Johannes Zuegg, Amy K. Cain, Alysha G. Elliott, Mark A. T. Blaskovich, Angelo Frei
Summary: Infections associated with antibiotic resistance (AMR) are projected to become the leading cause of death in the coming decades due to over-prescription of antibiotics and a lack of new drug development. A community-driven initiative, Community for Open Antimicrobial Drug Discovery (CO-ADD), has identified metal-based drugs as a potential and untapped source for combating AMR. Testing of 18 palladium (Pd) and ruthenium (Ru) complexes has revealed that Pd complexes, particularly Pd1, exhibit potent antifungal activity against Candida glabrata. Furthermore, in-vivo studies in Galleria mellonella larvae have demonstrated the non-toxic nature of these compounds.
Article
Chemistry, Physical
Joanna Bojarska, Martin Breza, Milan Remko, Ye Yuan, Zyta M. Ziora, Tsun-Thai Chai, Izabela D. Madura, Krzysztof Kaczmarek, Mark A. T. Blaskovich, Wojciech M. Wolf
Summary: A supramolecular behavior of a newly synthesized compound and a library of tetrazole-based H-bonding synthons were studied by X-ray crystallography and computational techniques. The supramolecular assembly was controlled by various interactions, including O...H, N...H, C...H, and pi-stacking interactions. The 3D topologies of the supramolecular architectures were visualized and dispersion forces played a crucial role. Quantum-chemical treatment revealed the chemical activity and stability of the compound. These findings provide valuable information for the design of therapeutic agents containing tetrazole motifs.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Review
Biochemistry & Molecular Biology
Angela A. Salim, Mark S. Butler, Mark A. T. Blaskovich, Ian R. Henderson, Robert J. Capon
Summary: This review summarizes all natural products (500 compounds, including 17 semi-synthetic derivatives) reported in the primary literature up to December 2022 that have been shown to inhibit the egg hatching, motility, larval development, and/or survival of helminths (nematodes, flukes, and tapeworms). These parasites infect and harm the health, welfare, productivity, and lives of commercial livestock, companion animals, and other valuable, endangered, and exotic animals. The review focuses on chemical structures, source organisms, and anthelmintic properties, including the target species, animal hosts, and potency measures used in bioassays.
NATURAL PRODUCT REPORTS
(2023)
Review
Biochemistry & Molecular Biology
Beth Rayner, Anthony D. Verderosa, Vito Ferro, Mark A. T. Blaskovich
Summary: Antimicrobial resistance poses a global threat due to the rise of multi-drug resistant bacteria and the lack of new antibiotics. The 'Trojan horse' approach, which uses bacteria's iron transport system to deliver antibiotics, shows promise in combating this issue. The use of siderophore antibiotic conjugates, such as cefiderocol, has proven to be effective against resistant bacteria. This review discusses recent advancements in these conjugates and the challenges in their design for more efficacious therapies.
RSC MEDICINAL CHEMISTRY
(2023)
