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
Infectious Diseases
Martyna Kasela, Mateusz Ossowski, Ewelina Dzikon, Katarzyna Ignatiuk, Lukasz Wlazlo, Anna Malm
Summary: Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of infectious diseases in humans and animals, resulting in economic losses in human healthcare and the farming sector. The changing epidemiology of MRSA globally affects animal welfare and public health concerns. Livestock have high rates of MRSA colonization, raising questions about reservoirs and transmission, while companion animals vary in MRSA colonization and infection rates, impacting human health. This article highlights the circulation of animal-associated MRSA (AA-MRSA) in the environment and factors influencing its transmission, as well as successful strategies to limit its spread among animals and humans.
Article
Biochemistry & Molecular Biology
Marta Woroszylo, Daria Ciecholewska-Jusko, Adam Junka, Radoslaw Drozd, Marcin Wardach, Pawel Migdal, Patrycja Szymczyk-Ziolkowska, Daniel Styburski, Karol Fijalkowski
Summary: The combination of rotating magnetic field (RMF) with beta-lactam antibiotics shows promising results in enhancing the antibacterial effects against methicillin-resistant Staphylococcus aureus (MRSA) by causing morphological alterations in bacterial cells. This study provides potential new treatment options for MRSA infections by utilizing the disruptive effect of RMF on bacterial cell walls.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Agriculture, Dairy & Animal Science
Pengfei Zhang, Xinyu Liu, Jie Zhang, Xueting Fu, Yangli Wan, Hu Pan, Congming Wu, Xin Wang
Summary: The study found that yak butter from Tibet, China, is contaminated with Staphylococcus aureus, including methicillin-resistant strains. The isolates carried various virulence genes, with blaZ being the most frequently detected resistance gene.
JOURNAL OF DAIRY SCIENCE
(2021)
Article
Immunology
Philip Nikolic, Poonam Mudgil, David G. Harman, John Whitehall
Summary: This study aimed to identify and compare the general differences in protein profiles among clinical strains of S. aureus sensitive and resistant to methicillin. The proteomic analysis revealed differences in protein abundances related to virulence, metabolism, and protein synthesis between MSSA and MRSA strains.
MICROBIAL PATHOGENESIS
(2023)
Article
Biochemistry & Molecular Biology
Muhammad Mubashar Idrees, Khadija Saeed, Muhammad Akbar Shahid, Muhammad Akhtar, Khadija Qammar, Javariya Hassan, Tayyaba Khaliq, Ali Saeed
Summary: This cross-sectional study aimed to determine the prevalence of mecA and mecC genes among phenotypically identified MRSA and evaluate their effectiveness against different antibiotics. The results showed a high prevalence of mecA and mecC in MRSA samples, and penicillin and amoxicillin/clavulanic acid were ineffective against MRSA, while vancomycin, teicoplanin, and linezolid were the most effective drugs.
Article
Public, Environmental & Occupational Health
Sara Quero, Marina Serras-Pujol, Noemi Parraga-Nino, Carmen Torres, Marian Navarro, Anna Vilamala, Emma Puigoriol, Javier Diez de los Rios, Elisenda Arque, Judit Serra-Pladevall, Alba Romero, Daniel Molina, Roger Paredes, Maria Luisa Pedro-Botet, Esteban Reynaga
Summary: This study investigated the prevalence of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) among workers in the pork production chain. The results showed that the prevalence of MRSA was high among workers in contact with live animals, especially in pig farms, livestock transporters, and slaughterhouses.
Article
Environmental Sciences
Anne Mette Madsen, Fei Zhang, Yonghui Zeng, Margit W. Frederiksen
Summary: This study investigated the potential human exposure to airborne microorganisms, including MRSA, in a pigeon exhibition in Denmark. The results showed high concentrations of fungi, bacteria, and endotoxin in the air, with concentrations up to 200 times higher than outdoor references. The bacteria found in the exhibition were mainly species found in pigeon coops, indicating that pigeons are the sources of exposure. The presence of airborne MRSA highlights the importance of considering this environment as a potential place of exchange of resistant bacteria between animals and humans.
ENVIRONMENTAL RESEARCH
(2023)
Article
Microbiology
Mohamad Hamad, Farah Al-Marzooq, Vunnam Srinivasulu, Hany A. Omar, Ashna Sulaiman, Dana M. Zaher, Gorka Orive, Taleb H. Al-Tel
Summary: We report the discovery of a new class of potent antimicrobial compounds effective against Gram-positive bacteria, including MRSA. These compounds exhibit low minimum inhibitory concentrations and rapid killing ability, without inducing bacterial resistance. Furthermore, they show minimal toxicity to human red blood cells. The study suggests that these small molecules hold promise as new antibacterial agents against MRSA infections.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Microbiology
Sarah E. Sansom, Emily Benedict, Stephanie N. Thiede, Bala Hota, Alla Aroutcheva, Darjai Payne, Chad Zawitz, Evan S. Snitkin, Stefan J. Green, Robert A. Weinstein, Kyle J. Popovich
Summary: This study utilized whole-genome sequencing to distinguish MRSA isolates, showing that a combination of clindamycin or levofloxacin susceptibility and resistance to <= 2 antibiotic classes can predict USA300 and USA100 strains. Additionally, resistance to <= 2 classes was found to be predictive for USA300 strains.
MICROBIOLOGY SPECTRUM
(2021)
Article
Microbiology
Kuan-Yi Lu, Nikki J. Wagner, Amanda Z. Velez, Agathe Ceppe, Brian P. Conlon, Marianne S. Muhlebach
Summary: MRSA infections are common and chronic in cystic fibrosis patients but are often resistant to antibiotic therapy. This study investigated whether bacterial phenotypes could predict the clinical outcomes of MRSA infections. The results showed no associations between these phenotypes and MRSA clearance, suggesting that additional factors may be relevant for predicting the clearance of MRSA.
MICROBIOLOGY SPECTRUM
(2023)
Article
Chemistry, Medicinal
Onanong Vorasin, Khanchyd Momphanao, Praewpan Katrun, Chutima Kuhakarn, Chutima Jiarpinitnun
Summary: The study identified a range of potential antibacterial vinyl sulfone derivatives, with nitrile-substituted vinyl phenyl sulfones showing the strongest activity and potentially functioning through sulfhydryl conjugation. Additionally, these compounds could also affect host cell adhesion, suggesting promising therapeutic potential for S. aureus and MRSA.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Microbiology
Karina M. S. Herrera, Gabriela F. M. Lopes, Michael E. Oliveira, Jaqueline F. Sousa, William G. Lima, Fernanda K. Silva, Julio C. M. Brito, Ana Julia P. S. Gomes, Gustavo H. R. Viana, Adriana C. Soares, Jaqueline M. S. Ferreira
Summary: This study evaluated the antibacterial activity of five 3-alkyl-pyridinic analogs against MRSA. Compound 6 showed promising antibacterial activity, exhibited a rapid bactericidal action, and had low resistance induction potential. It also showed an additive effect when combined with other antibiotics.
MICROBIOLOGICAL RESEARCH
(2022)
Review
Infectious Diseases
Joshua. B. Parsons, Annette. C. Westgeest, Brian. P. B. Conlon, Vance. G. Fowler
Summary: Methicillin-resistant Staphylococcus aureus (MRSA) is a deadly pathogen that can persist in the bloodstream for days despite appropriate antibiotics. Persistent MRSA bacteremia is common and associated with poor clinical outcomes. This review explores the factors related to host-pathogen interaction and discusses the clinical relevance of each element. Treatment options and diagnostic approaches for managing persistent MRSA bacteremia are also discussed.
Article
Chemistry, Medicinal
Carly Deusenbery, Olivia Carneiro, Carleigh Oberkfell, Anita Shukla
Summary: This study evaluated the synergistic eradication mechanism of six compounds in nine combinations against MRSA biofilms. Two promising combinations of antibiotics and antibiofilm agents were identified, providing insight for the development of effective treatments against MRSA biofilms.
ACS INFECTIOUS DISEASES
(2023)
Article
Chemistry, Organic
Dominik Jankovi, Miha Virant, Martin Gazvoda
Summary: In this study, we report a sustainable copper-catalyzed reaction that forms 4-substituted-1H-1,2,3-triazoles through a cycloaddition of hydrogen azide with terminal alkynes. The reaction proceeds under mild conditions, using polydentate N-donor chelating ligands and mild organic acids. High yields of the desired triazoles are achieved with low catalyst loadings. This method shows excellent functional group tolerance and is applicable for late-stage functionalization in organic synthesis.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Materials Science, Multidisciplinary
Chengxiong Wei, Xin Jin, Chengwei Wu, Anamaria Brozovic, Wei Zhang
Summary: In this study, carbon spheres with good photothermal effect were rapidly synthesized by pyrolysis of pyrogallol-formaldehyde spheres. The carbon spheres exhibited a high photothermal conversion efficiency of 54.2% and showed good cell biocompatibility for tumor tissue ablation.
DIAMOND AND RELATED MATERIALS
(2022)
Article
Oncology
Juran Kralj, Margareta Pernar Kovac, Sanja Dabelic, Darija Stupin Polancec, Thorsten Wachtmeister, Karl Koehrer, Anamaria Brozovic
Summary: A novel OC cell model was established, and two transcriptome analysis approaches identified TMEM200A and PRKAR1B as important genes in carboplatin resistance and metastasis, with high predictive and prognostic values for OC patients. Compared to parental cells, carboplatin-resistant cells showed increased sensitivity to PI3K/Akt/mTOR pathway inhibitors and enhanced sensitivity to carboplatin when treated with a transcription inhibitor.
BRITISH JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Ivana Fabijanic, Atanas Kurutos, Ana Tomasic Paic, Vanja Tadic, Fadhil S. Kamounah, Lucija Horvat, Anamaria Brozovic, Ivo Crnolatac, Marijana Radic Stojkovic
Summary: The binding interactions of six ligands with various nucleic acid structures were evaluated using fluorescence, UV/Vis, and circular dichroism spectroscopy. The results showed that the cyanine dyes bind with G-quadruplex structures through end pi-pi stacking interactions and possible additional interactions with the nucleobases/phosphate backbone. The ability of cyanines to distinguish different nucleic acid structures was demonstrated by their varying ICD signals. Additionally, the cyanines exhibited inhibitory effects on cell viability and showed potential as theranostic agents.
Article
Multidisciplinary Sciences
Carmina Micelli, Yunfei Dai, Nicole Raustad, Ralph R. Isberg, Christopher G. Dowson, Adrian J. Lloyd, Edward Geisinger, Allister Crow, David I. Roper
Summary: Acinetobacter baumannii is a gram-negative bacterial pathogen that causes challenging nosocomial infections. The study reveals the molecular details of cell wall elongation inhibition upon zinc starvation in A. baumannii. The findings offer a perspective for dual inhibition of zinc-dependent peptidoglycan synthases and metallo-beta-lactamases by metal-chelating agents.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Jonathan Cook, Tyler C. Baverstock, Martin B. L. McAndrew, David I. Roper, Phillip J. Stansfeld, Allister Crow
Summary: AmiA and AmiB are enzymes from Escherichia coli that break the peptidoglycan layer and maintain cell integrity. Their activity is controlled by interactions with the FtsEX-EnvC complex. The structures of AmiA and AmiB in different states were determined, revealing the conformational changes required for activation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Multidisciplinary
Anze Ivancic, Janez Kosmrlj, Martin Gazvoda
Summary: In the synergistic dual catalytic process, it is crucial to balance the kinetics of the catalytic cycles for a successful reaction. This study analyzed the mechanism of a palladium-catalyzed cross-coupling reaction, providing insights into the elementary steps and kinetics of each step.
COMMUNICATIONS CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Margareta Pernar Kovac, Vanja Tadic, Juran Kralj, Marija Milkovic Perisa, Slavko Oreskovic, Ivan Babic, Vladimir Banovic, Wei Zhang, Zoran Culig, Anamaria Brozovic
Summary: Through high-throughput miRNA and cDNA profiling, pathway analysis, and data mining, epigenetically regulated miRNAs were identified in drug-resistant, mesenchymal-like ovarian cancer cells, which may serve as markers to combat therapy-induced short-term survival and tumor metastatic potential.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Margareta Pernar Kovac, Vanja Tadic, Juran Kralj, George E. Duran, Alessia Stefanelli, Darija Stupin Polancec, Sanja Dabelic, Niko Bacic, Maja T. Tomicic, Petra Heffeter, Branimir I. Sikic, Anamaria Brozovic
Summary: This study investigated resistance to platinum and taxane-based chemotherapy in ovarian cancer cells and the role of TUBB3 in therapy response prediction.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Chemistry, Medicinal
Christian Steinebach, Alesa Bricelj, Arunima Murgai, Izidor Sosic, Luca Bischof, Yuen Lam Dora Ng, Christopher Heim, Samuel Maiwald, Matic Proj, Rabea Voget, Felix Feller, Janez Kosmrlj, Valeriia Sapozhnikova, Annika Schmidt, Maximilian Rudolf Zuleeg, Patricia Lemnitzer, Philipp Mertins, Finn K. Hansen, Michael Guetschow, Jan Kroenke, Marcus D. Hartmann
Summary: This study developed novel nonphthalimide CRBN binders by optimizing physiochemical properties, stability, on-target affinity, and off-target neosubstrate modulation features. These binders exhibited enhanced chemical stability and favorable selectivity in neosubstrate recruitment, providing opportunities for the design of highly selective and potent chemically inert compounds.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Sasa Opacak, Margareta Pernar Kovac, Anamaria Brozovic, Ivo Piantanida, Srecko I. Kirin
Summary: Two novel pyrene triphenylphosphine ruthenium conjugates function as fluorescent turn-on beacons for serum albumin, exhibiting strong emission upon binding to BSA while being non-fluorescent in aqueous media. The compounds' selective cytotoxicity against tumour cells is enhanced under UV-light irradiation, suggesting potential application in two-photon excited photodynamic therapy.
DALTON TRANSACTIONS
(2023)
Article
Urology & Nephrology
Beate Koeberle, Svetlana Usanova, Andrea Piee-Staffa, Ulrike Heinicke, Philipp Clauss, Anamaria Brozovic, Bernd Kaina
Summary: Metastatic testicular germ cell tumors (TGCT) are sensitive to cisplatin-based combination therapy due to activation of apoptotic pathways and limited DNA repair, while other solid metastatic cancers are resistant to chemotherapy.
INTERNATIONAL UROLOGY AND NEPHROLOGY
(2023)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)