Article
Biochemistry & Molecular Biology
Azza Troudi, Jean Michel Bolla, Naouel Klibi, Jean Michel Brunel
Summary: Gram-negative bacteria pose a significant threat to public health due to the spread of drug resistance and the lack of effective alternative treatments. This study presents a promising strategy to combat resistant strains by combining a macrolide antibiotic with a polyaminoisoprenyl adjuvant derivative, resulting in a significant decrease in antibiotic resistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Rajib Dey, Sudip Mukherjee, Riya Mukherjee, Jayanta Haldar
Summary: Gram-negative bacterial infections with significant antibiotic resistance can be effectively treated by combining obsolete antibiotics with non-antibiotic adjuvants that target bacterial membranes. The development of a small molecular adjuvant with moderate membrane perturbation in bacterial cells and no toxicity to mammalian cells enhances the internalization of antibiotics and inhibits the efflux machinery, revitalizing the efficacy of various classes of antibiotics. This combination therapy demonstrates potent bactericidal activity against biofilms and multi-drug resistant infections, with good biocompatibility and antibacterial efficacy. The study highlights the potential of this approach for treating multi-drug resistant infections.
Article
Chemistry, Multidisciplinary
Michael J. Zeiler, Gina M. Connors, Greg M. Durling, Allen G. Oliver, Lewis Marquez, Roberta J. Melander, Cassandra L. Quave, Christian Melander
Summary: Antibiotic resistance has become a serious problem, requiring new approaches to combat infections caused by resistant bacteria. One such approach is the development of small molecules called adjuvants, which enhance the activity of conventional antibiotics. This study discovered a natural product called (-)-LZ-2112 that synergizes with oxacillin to fight against methicillin-resistant Staphylococcus aureus. Further research identified key structural elements of (-)-LZ-2112 and suggested the possibility of simplifying its structure.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Engineering, Biomedical
Umesh Chand, Pramod Kumar Kushawaha
Summary: Antimicrobial resistance is a growing problem and the use of immunomodulators combined with nanotechnology can be an effective strategy to combat drug-resistant bacterial infections.
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
(2023)
Article
Chemistry, Multidisciplinary
Abdulaziz H. Alkhzem, Maisem Laabei, Timothy J. Woodman, Ian S. Blagbrough
Summary: Antibiotic resistance poses an increasingly serious threat to human health, and the lack of new antibiotics exacerbates this issue. This study presents a practical synthesis method for potential new antibiotics, capable of combating various bacteria including MRSA and Pseudomonas aeruginosa. By utilizing specific synthesis techniques, the antimicrobial activity of the antibiotics can be enhanced.
Article
Chemistry, Medicinal
Geetika Dhanda, Riya Mukherjee, Debajyoti Basak, Jayanta Haldar
Summary: This article discusses the prospects and challenges of combination therapy with membrane-targeting compounds in the treatment of multidrug-resistant bacterial infections, as well as the structural influence on membrane perturbation, activity, and toxicity of antibiotic potentiators or adjuvants. By incorporating cyclic hydrophobic moieties, antibiotic adjuvants with weak membrane perturbation and negligible in vitro toxicity but good potentiating ability have been developed. Aryl or adamantane functionalized derivatives showed better potentiation, increasing the sensitivity of critical Gram-negative superbugs to multiple classes of antibiotics. The mechanism of potentiation involved weak outer-membrane permeabilization, membrane depolarization, and efflux inhibition. This concept of weakly perturbing the membrane through chemical design has the potential to revitalize the effectiveness of obsolete antibiotics for the treatment of complicated Gram-negative bacterial infections.
ACS INFECTIOUS DISEASES
(2022)
Article
Microbiology
Qin Dou, Yuxiang Zhu, Chunhui Li, Zeran Bian, Huihui Song, Ruizhen Zhang, Yingsong Wang, Xile Zhang, Yan Wang
Summary: The combination of halogenated indoles and aminoglycoside antibiotics can enhance the effectiveness against Pseudomonas aeruginosa PAO1 and uncover the mechanism of the regulatory effect induced by 4F-indole.
MICROBIOLOGY SPECTRUM
(2023)
Editorial Material
Oncology
Natasha E. Weiser, King L. Hung, Howard Y. Chang
Summary: Extrachromosomal DNA circles (ecDNA) serve as a common mechanism for oncogene amplification and are associated with worse clinical outcomes. Recent discoveries of ecDNA hubs in the nucleus reveal unique features that contribute to higher oncogene expression and rapid tumor evolution.
Article
Infectious Diseases
Lorenza Fagnani, Lisaurora Nazzicone, Fabrizia Brisdelli, Luisa Giansanti, Sara Battista, Roberto Iorio, Sabrina Petricca, Gianfranco Amicosante, Mariagrazia Perilli, Giuseppe Celenza, Pierangelo Bellio
Summary: The study indicates that combining antibiotics with amphoteric surfactants is a promising therapeutic option for infections caused by multidrug-resistant S. aureus. Among the compounds tested, L-prolinol amine-oxide C12NOX showed the most promising results. This research provides valuable insights into combating antibiotic resistance in pathogenic bacteria.
Article
Biotechnology & Applied Microbiology
Amlan Talukder, Haiyan Hu, Xiaoman Li
Summary: By studying IEPs in nine cell lines and nine primary cell types, it was found that enhancers may form clusters, with enhancers in the same cluster interacting synchronously with a set of genes and potentially being up to two million base pairs away from each other. While some clusters of enhancers overlap with super-enhancers, the majority of enhancer clusters are distinct from known super-enhancers.
Review
Infectious Diseases
Pier Carmine Passarelli, Andrea Netti, Michele Antonio Lopez, Eleonora Favetti Giaquinto, Giuseppe De Rosa, Gianmarco Aureli, Alina Bodnarenko, Piero Papi, Anna Starzynska, Giorgio Pompa, Antonio D'Addona
Summary: This study aimed to evaluate the effect of local/topical antibiotics for peri-implantitis treatment. While local antibiotic use can be considered a valid approach, contrasting results and high heterogeneity among studies suggest the need for future long-term clinical trials to achieve conclusive findings.
Article
Infectious Diseases
Diana Oliveira, Anabela Borges, Maria J. Saavedra, Fernanda Borges, Manuel Simoes
Summary: Diabetic foot ulcers are a common complication of diabetes and often become infected with Staphylococcus aureus. This study investigates the use of phytochemicals and derivatives as antibiotic enhancers to combat multidrug resistance in bacterial wound infections.
Article
Biochemical Research Methods
Antonios Klonizakis, Christoforos Nikolaou, Thomas Graf
Summary: SEGCOND is a computational framework aiming to identify genomic regions involved in the formation of transcriptional condensates. It combines multiple genomic datasets for genome segmentation and utilizes Hi-C data to identify putative transcriptional condensates. When applied to data from B-cell to macrophage transdifferentiation, SEGCOND identified new genes with potential roles in the process.
Article
Cell Biology
Yangtao Wu, Xiaofen Huang, Lunzhi Yuan, Shaojuan Wang, Yali Zhang, Hualong Xiong, Rirong Chen, Jian Ma, Ruoyao Qi, Meifeng Nie, Jingjing Xu, Zhigang Zhang, Liqiang Chen, Min Wei, Ming Zhou, Minping Cai, Yang Shi, Liang Zhang, Huan Yu, Junping Hong, Zikang Wang, Yunda Hong, Mingxi Yue, Zonglin Li, Dabing Chen, Qingbing Zheng, Shaowei Li, Yixin Chen, Tong Cheng, Jun Zhang, Tianying Zhang, Huachen Zhu, Qinjian Zhao, Quan Yuan, Yi Guan, Ningshao Xia
Summary: This study developed a protein subunit vaccine consisting of spike ectodomain protein and a nitrogen bisphosphonate-modified zinc-aluminum hybrid adjuvant, which showed higher neutralizing antibody titers in animal models and induced T cell responses. The vaccine provided protection against SARS-CoV-2 challenge and reduced virus transmission among vaccinated and unvaccinated animals.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Chemistry, Organic
Luo-Rong Yuan, Shun-Jun Ji, Xiao-Ping Xu
Summary: In this study, a cobalt-catalyzed coupling-cyclization cascade reaction was investigated, which allowed for the synthesis of various spiroindoline compounds by modifying substituents at the N1- and C2-positions in the indole skeleton. Interestingly, the spiroindoline products could undergo despirocyclization in the presence of amines, enabling efficient construction of enamine compounds.
Article
Biochemistry & Molecular Biology
Alex J. Lee, Melissa M. Cadelis, Sang H. Kim, Simon Swift, Brent R. Copp, Silas G. Villas-Boas
Article
Biochemistry & Molecular Biology
A. Norrie Pearce, Dan Chen, Liam R. Edmeades, Melissa M. Cadelis, Azza Troudi, Jean Michel Brunel, Marie-Lise Bourguet-Kondracki, Brent R. Copp
Summary: Evaluation of succinylprimaquine-polyamine conjugates identified two derivatives with intrinsic antimicrobial activity against Staphylococcus aureus and Cryptococcus neoformans. In the presence of doxycycline, these compounds also showed potent antibiotic adjuvant properties against Pseudomonas aeruginosa. Further studies explored the structure-activity relationship to enhance antimicrobial properties against P. aeruginosa.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Melissa M. Cadelis, Soeren Geese, Benedict B. Uy, Daniel R. Mulholland, Shara J. van de Pas, Alex Grey, Bevan S. Weir, Brent R. Copp, Siouxsie Wiles
Summary: Antimicrobial bioassay-guided fractionation of the endophytic fungi Neofusicoccum australe resulted in the isolation of a new unsymmetrical naphthoquinone dimer, neofusnaphthoquinone B (1), along with four known natural products. The antimicrobial activity of all the compounds was investigated, with compound 1 showing moderate activity against methicillin-resistant Staphylococcus aureus (MRSA) at a minimum inhibitory concentration of 16 μg/mL.
Article
Biochemistry & Molecular Biology
Melissa M. Cadelis, Hugo Gordon, Alex Grey, Soeren Geese, Daniel R. Mulholland, Bevan S. Weir, Brent R. Copp, Siouxsie Wiles
Summary: Fungi are a valuable source of bioactive natural products, and a recent study on Neodidymelliopsis sp. led to the discovery of several new compounds, including a polyketide that is sensitive to environmental conditions. Additionally, it was confirmed that pachybasin is biosynthesized through the acetate polyketide pathway.
Article
Biochemistry & Molecular Biology
Melissa M. Cadelis, Natasha S. L. Nipper, Alex Grey, Soeren Geese, Shara J. van de Pas, Bevan S. Weir, Brent R. Copp, Siouxsie Wiles
Summary: Screening of fungi from the New Zealand International Collection of Microorganisms from Plants identified two strains of Penicillium with antimicrobial activity. Further investigation led to the discovery of five known polyketide metabolites and a novel derivative. One of the polyketide metabolites and one derivative showed inhibitory activity against Methicillin-resistant Staphylococcus aureus.
Article
Biochemistry & Molecular Biology
Dan Chen, Daniel J. Park, Melissa M. Cadelis, Hana Douafer, Marie Lise Bourguet-Kondracki, Jean Michel Brunel, Brent R. Copp
Summary: Two diketopiperazine natural products were found to have antibacterial activity and enhance the action of antibiotics. However, the synthesized diastereomers did not exhibit the same properties, indicating that these compounds are not suitable templates for new treatments for microbial infections.
Article
Infectious Diseases
Steven A. Li, Rebecca J. Zheng, Kenneth Sue, Marie-Lise Bourguet-Kondracki, Azza Troudi, Jean Michel Brunel, Brent R. Copp, Melissa M. Cadelis
Summary: Antibiotics have played a crucial role in modern medicine, but the increasing prevalence of antibiotic-resistant bacteria has highlighted the urgent need for new antibiotics with novel mechanisms of action. In this study, researchers screened a library of compounds and identified two weak growth inhibitors that showed potential against methicillin-resistant Staphylococcus aureus (MRSA). Further evaluation led to the discovery of two analogues with favorable anti-MRSA activity and no cytotoxic or hemolytic properties. Additionally, the study also identified two derivatives that showed selective antifungal activity against Cryptococcus neoformans. These findings suggest that 3-substituted-1H-imidazol-5-yl-1H-indoles and 5-phenyl-1H-imidazoles could serve as promising structural scaffolds for the development of new anti-MRSA and anti-C. neoformans agents, respectively.
Article
Biochemistry & Molecular Biology
Melissa M. Cadelis, Steven A. Li, Shara J. van de Pas, Alex Grey, Daniel Mulholland, Bevan S. Weir, Brent R. Copp, Siouxsie Wiles
Summary: Various fungal plant pathogens were found to have antimicrobial activity against human pathogenic bacteria and resulted in the isolation of ten natural products, among which one was novel. Further investigation showed that some of these compounds exhibited potent activity against Methicillin resistant Staphylococcus aureus, Mycobacterium marinum, and Candida albicans, and one of them (10) was non-cytotoxic and non-haemolytic.
Article
Infectious Diseases
Melissa M. Cadelis, Liam R. Edmeades, Dan Chen, Evangelene S. Gill, Kyle Fraser, Florent Rouvier, Marie-Lise Bourguet-Kondracki, Jean Michel Brunel, Brent R. Copp
Summary: A series of naphthyl- and biphenyl-substituted polyamine conjugates were synthesized to search for new antimicrobials and antibiotic enhancers. Longer chain variants containing 1-naphthyl and 2-naphthyl capping groups showed strong intrinsic antimicrobial properties against MRSA and Cryptococcus neoformans. Some analogues in the set were able to enhance the antibiotic action of doxycycline and erythromycin towards Pseudomonas aeruginosa and Escherichia coli, with two analogues exhibiting more than 32-fold enhancement in activity. These findings suggest the potential of α,ω-disubstituted polyamines with 1-naphthyl- and 2-naphthyl-capping groups as non-toxic antibiotic enhancers.
Article
Chemistry, Medicinal
Melissa M. Cadelis, Tim Liu, Kenneth Sue, Florent Rouvier, Marie-Lise Bourguet-Kondracki, Jean Michel Brunel, Brent R. Copp
Summary: Antibiotic resistance is a growing global health threat. One approach to overcome this is to discover and develop new antibiotic enhancers that can enhance the efficacy of existing antibiotics against resistant bacteria.
Article
Biochemistry & Molecular Biology
Melissa M. Cadelis, Jisoo Kim, Florent Rouvier, Evangelene S. Gill, Kyle Fraser, Marie-Lise Bourguet-Kondracki, Jean Michel Brunel, Brent R. Copp
Summary: In this study, a set of analogues of ianthelliformisamine C were synthesized to investigate their antimicrobial activities and enhance the action of doxycycline against Pseudomonas aeruginosa. The results showed that the longest polyamine chain analogues without bromine atoms exhibited intrinsic antimicrobial activity, while all analogues with bromine atoms were active. However, many of these longer analogues showed cytotoxic and red blood cell hemolytic properties, limiting their potential as antimicrobial lead compounds. Two non-toxic, non-halogenated analogues were found to strongly enhance the action of doxycycline against P. aeruginosa.