Article
Biochemistry & Molecular Biology
Florin Aonofriesei
Summary: The combination of two compounds can effectively limit antibiotic resistance in specific pathogens, with surfactants enhancing the antibacterial effect by modifying the permeability of bacterial cells. This research highlights the possibility of using non-toxic surfactants to control microbial resistance and offers practical applications in the field of antimicrobials.
Review
Immunology
Arsheena Yassin, Mariya Huralska, Jason M. Pogue, Deepali Dixit, Robert G. Sawyer, Keith S. Kaye
Summary: The prevalence of multidrug-resistant gram-negative bacterial infections has significantly increased in the past decade, leading to higher rates of morbidity and mortality. Treating these infections presents challenges, particularly for critically ill patients with limited margin for error. The availability of new therapies has improved treatment options, but optimal clinical and therapeutic approaches for managing these infections still need to be established.
CLINICAL INFECTIOUS DISEASES
(2023)
Review
Pharmacology & Pharmacy
Chuanhai Wang, Deqing Yang, Yifan Wang, Wentao Ni
Summary: Cefiderocol is a promising powerful weapon for treating multidrug-resistant (MDR) infections, showing high in vitro and in vivo activity, especially against carbapenem-resistant isolates. Clinical trials have demonstrated its efficacy in treating complicated urinary tract infection and nosocomial pneumonia.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Microbiology
Yuvaneswary Veloo, Syahidiah S. A. Thahir, Sakshaleni Rajendiran, Lim K. Hock, Norazah Ahmad, Vickneshwaran Muthu, Rafiza Shaharudin
Summary: The indiscriminate use of antibiotics in poultry farming has led to the emergence of antibiotic-resistant bacteria in poultry products and the surrounding environment. This study found high rates of multidrug-resistant Gram-negative bacteria in the environment of poultry farms, with some strains exhibiting resistance to multiple antibiotics. The presence of these bacteria poses a significant threat to the effectiveness of available antibiotics in treating infectious diseases. Efforts to regulate antibiotic use and conduct research on One Health issues are necessary to combat and prevent the spread of antibiotic-resistant bacteria.
MICROBIOLOGY SPECTRUM
(2022)
Article
Biochemistry & Molecular Biology
Romana Vrzonova, Alzbeta Cizova, Lucia Rackova, Jana Mecarova, Sandra Bielikova, Slavomir Bystricky
Summary: The rise of multidrug-resistant bacteria has increased the demand for new biocompatible and biodegradable antibacterial compounds. Cationic polysaccharides, such as derivatives of commercial dextrans, show promising antimicrobial properties. The study found that derivatives with higher degree of substitution and varying molar masses had better antimicrobial efficiency. However, as the molar mass increased, the biocompatibility of the cationic dextran decreased, showing hemagglutination and toxicity to human cells. The derivatives of 76 kDa dextran with higher degree of substitution were identified as the best antimicrobial agents for further clinical testing.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Review
Microbiology
Gang Zhou, Qian Wang, Yingsi Wang, Xia Wen, Hong Peng, Ruqun Peng, Qingshan Shi, Xiaobao Xie, Liangqiu Li
Summary: This review examines the properties and interactions of five common outer membrane proteins (Omps), including OmpA, OmpC, OmpF, OmpW, and OmpX, in relation to porin-mediated permeability in gram-negative bacteria. It also highlights the discovered regulatory characteristics and identified molecular mechanisms in antibiotic penetration through Omps. Uncovering the functional properties of Omps will pave the way for investigating effective agents or approaches that use Omps as targets to eliminate resistant gram-negative bacteria.
Article
Public, Environmental & Occupational Health
Z. Elnasser, R. Elsamarneh, H. Obeidat, Z. Amarin, S. Jaradat, N. Kaplan
Summary: The study identified multidrug-resistant Gram negative bacteria isolates with high resistance to various antibiotics, including approximately 21.4% resistance to tigecycline. These pathogens also carried resistance-related genes such as AcrB, RamR, and TetA.
JOURNAL OF INFECTION AND PUBLIC HEALTH
(2021)
Article
Microbiology
Christine A. Pybus, Christina Felder-Scott, Victor Obuekwe, David E. Greenberg
Summary: The study compared the antimicrobial activity of Cefiderocol with seven commonly used antibiotics against multidrug-resistant pathogens, finding that Cefiderocol had potent inhibitory effects on biofilms of various pathogens, with consistently lower MIC90 values compared to other antibiotics.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Weijie Wang, Xiaoli Zhu, Huan Luo, Zheng Wang, Anjin Hong, Jie Zeng, Li Li, Dai Wang, Xianming Deng, Xilin Zhao
Summary: As the increase in antimicrobial resistance continues, the options for effectively treating multidrug-resistant (MDR) Gram-negative infections are decreasing. Finding ways to enhance the lethality of old agents with unique molecular targets is important, as new antimicrobial development is increasingly difficult. This study showed that the old antibiotic bicyclomycin has good bacteriostatic activity against multiple clinical isolates of MDR Gram-negative pathogens. Additionally, the combination of bicyclomycin with doxycycline showed enhanced efficacy in inhibiting bacterial growth and in vivo killing, suggesting the potential of bicyclomycin-containing regimens as new treatment options for MDR Gram-negative infections caused by specific pathogens.
MICROBIOLOGY SPECTRUM
(2023)
Article
Chemistry, Medicinal
Kenneth I. Onyedibe, Ansley M. Nemeth, Neetu Dayal, Richard D. Smith, Jones Lamptey, Robert K. Ernst, Roberta J. Melander, Christian Melander, Herman O. Sintim
Summary: Researchers have discovered a compound called HSD1624 that enhances the effectiveness of the antibiotic colistin against resistant bacteria in multiple strains.
ACS INFECTIOUS DISEASES
(2023)
Review
Infectious Diseases
Sisi Zhen, Hui Wang, Sizhou Feng
Summary: CAZ-AVI is a valuable therapeutic option for MDR-GNB infections, particularly for KPC or OXA-48 CRE infections. It shows significant benefits and improved clinical outcomes, even in immunocompromised patients. Early use of CAZ-AVI is associated with better efficacy. However, resistance development in CRE and MDR-PA against CAZ-AVI is a concern, and further investigations are needed.
Article
Chemistry, Medicinal
Yasunari Otsuka, Eijiro Umemura, Yukimi Takamiya, Teruhisa Ishibashi, Chigusa Hayashi, Keiko Yamada, Masayuki Igarashi, Masakatsu Shibasaki, Yoshiaki Takahashi
Summary: Novel aprosamine derivatives were synthesized and showed excellent antibacterial activity against multidrug-resistant Gram-negative and Gram-positive bacteria. The derivatives exhibited higher activity compared to the clinical drug arbekacin, indicating their potential as therapeutic agents for multidrug-resistant bacteria.
ACS INFECTIOUS DISEASES
(2023)
Article
Immunology
Sharon Ong'uti, Mary Czech, Elizabeth Robilotti, Marisa Holubar
Summary: Cefiderocol, a novel injectable siderophore cephalosporin, is effective against multidrug-resistant gram-negative bacteria by hijacking the bacterial iron transport system. It has broad-spectrum antibacterial activity, including against carbapenem-resistant and Acinetobacter baumannii strains.
CLINICAL INFECTIOUS DISEASES
(2022)
Letter
Immunology
Ashka Patel, Michele Emerick, Marie K. Cabunoc, Michelle H. Williams, Michael Anne Preas, Gregory Schrank, Ronald Rabinowitz, Paul Luethy, J. Kristie Johnson, Surbhi Leekha
Summary: The rapid spread of multidrug-resistant gram-negative bacteria among patients in a dedicated coronavirus disease care unit in a Maryland hospital was attributed to factors such as critical illness, high antibiotic use, double occupancy of single rooms, and modified infection prevention practices. Surveillance culturing played a key role in identifying and controlling the outbreak.
EMERGING INFECTIOUS DISEASES
(2021)
Article
Microbiology
Yuhang Wang, Junfeng Su, Ziyan Zhou, Jie Yang, Wenjuan Liu, Yafen Zhang, Pengyu Zhang, Tingting Guo, Guocai Li
Summary: As multidrug-resistant pathogens emerge and spread rapidly, novel antibiotics are urgently needed. Traditional Chinese medicine, such as baicalein, can be used as an adjuvant to enhance the efficacy of antibiotics. Baicalein was found to potentiate doxycycline against multidrug-resistant Gram-negative pathogens by disrupting the bacterial membrane and enhancing antibiotic entry. It can also increase the production of reactive oxygen species and inhibit multidrug efflux pumps and biofilm formation to potentiate antibiotic efficacy.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemistry & Molecular Biology
Aneta Kaczor, Karolina Witek, Sabina Podlewska, Veronique Sinou, Joanna Czekajewska, Ewa Zeslawska, Agata Doroz-Plonka, Annamaria Lubelska, Gniewomir Latacz, Wojciech Nitek, Markus Bischoff, Sandrine Alibert, Jean-Marie Pages, Claus Jacob, Elzbieta Karczewska, Jean-Michel Bolla, Jadwiga Handzlik
Summary: New morpholine-containing compounds were explored as potential antibiotic adjuvants against Gram-positive and Gram-negative bacteria, with some compounds showing promising results in overcoming antibiotic resistance. Molecular modelling and experimental testing confirmed their mechanisms of action, while also demonstrating significant MDR-reversal dual action and inhibition of efflux pumps in resistant bacteria.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Azza Troudi, Jean Marie Pages, Jean Michel Brunelx
Summary: The outer membrane of Gram-negative bacteria serves as an efficient barrier against external harmful compounds and plays a crucial role in preventing the entry of antimicrobial agents. Current antibiotics mainly target intracellular components, requiring translocation across membranes. A better understanding of Lipid A synthesis and membrane assembly could lead to the development of new antibacterial drugs against microbial resistance.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Erika Boulant, Emmanuelle Cambon, Julia Vergalli, Remi Bernard, Fabienne Neulat-Ripoll, Flora Nolent, Olivier Gorge, Maria Girleanu, Anne-Laure Favier, Jean-Paul Leonetti, Jean Michel Bolla
Summary: This study focused on enhancing the tolerance of Deinococcus geothermalis for industrial production by introducing heterologous efflux pump genes. By selecting resistant recombinants and conducting efficiency tests, the compound efflux in the hit recombinant was significantly increased, laying the foundation for efficient production in D. geothermalis.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Ana-Maria Udrea, Andra Dinache, Jean-Marie Pages, Ruxandra Angela Pirvulescu
Summary: The study investigates the potential of BG1189 and BG1190 as efflux pump inhibitors through in silico and molecular docking approaches. The findings suggest that these compounds could be attractive candidates for antimicrobial drugs. UV-Vis absorption spectroscopy and FTIR spectroscopy were utilized to study the stability and effects of laser radiation on the molecules.
Review
Infectious Diseases
Anne Davin-Regli, Jean-Marie Pages, Aurelie Ferrand
Summary: Antibiotic efflux is a well-documented mechanism in bacteria for multidrug resistance, facilitating adaptation to high concentrations of antibiotics. Efflux pumps are frequently found in Gram-negative bacteria and expel a wide range of antibiotics, but there is currently no real-time quantification method. The development of a routine diagnostic tool is urgently needed for the rational use of antibiotics.
Article
Engineering, Biomedical
Robert Richter, Mohamed A. M. Kamal, Marcus Koch, Bart-Jan Niebuur, Anna-Lena Huber, Adriely Goes, Carsten Volz, Julia Vergalli, Tobias Kraus, Rolf Mueller, Nicole Schneider-Daum, Gregor Fuhrmann, Jean-Marie Pages, Claus-Michael Lehr
Summary: In this study, outer membrane vesicles (OMVs) from E. coli were utilized as a model to predict drug uptake across the complex cell envelope, showing a better correlation with reported bacterial accumulation data and the ability to discriminate high from low accumulating antibiotics. This approach offers a potential high throughput screening tool with high predictive capacity for identifying compound- and bacteria-specific passive uptake pathways in the future.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Biology
Julia Vergalli, Hugo Chauvet, Francesco Oliva, Jelena Pajovic, Giuliano Malloci, Attilio Vittorio Vargiu, Matthieu Refregiers, Paolo Ruggerone, Jean-Marie Pages
Summary: This study combines experimental and computational approaches to reveal the interaction and molecular mechanism between quinolone antibiotics and bacterial multidrug efflux pumps. The findings are important for optimizing antibiotics and can be extended to the study of other efflux pumps.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biology
Muriel Masi, Julia Vergalli, Ishan Ghai, Andrea Barba-Bon, Therese Schembri, Werner M. Nau, Daniel Lafitte, Mathias Winterhalter, Jean-Marie Pages
Summary: This study investigated the translocation and killing effects of different cephalosporins on Gram-negative bacteria. The results revealed that the activity and efficiency of the drugs were influenced by the expression of specific porins. Through experimentation and analysis, it was found that the net negative charge of one of the cephalosporins contributed to its higher permeation through less cation-selective porins. These findings provide insights into the susceptibility of specific bacteria strains to cephalosporins.
COMMUNICATIONS BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Jinane Tabcheh, Julia Vergalli, Anne Davin-Regli, Noha Ghanem, Jean-Marie Pages, Charbel Al-Bayssari, Jean Michel Brunel
Summary: Antibiotic resistance is increasing morbidity and mortality for non-curable infectious diseases. Novel strategies, such as effective antibiotic combinations and antibiotics with non-antibiotic activity-enhancing compounds, have emerged to combat multidrug-resistant microorganisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Infectious Diseases
Aurelie Ferrand, Julia Vergalli, Claude Bosi, Alix Pantel, Jean-Marie Pages, Anne Davin-Regli
Summary: The emergence of MDR strains poses a public health problem. The role of antibiotic efflux in bacterial resistance is often underestimated, leading to misinterpretation of resistance phenotypes. We developed a diagnostic system to quantify efflux and improve patient management.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Integrative & Complementary Medicine
Rene Dofini Magnini, Mathieu Nitiema, Geoffroy G. Ouedraogo, Sylvain Ilboudo, Alimata Bance, Hassanata Millogo-Kone, Carole Di Giorgio, Jean-Marie Pages, Adama Hilou, Anne Davin-Regli
Summary: The hydroethanolic extract of Acacia senegal leaves has significant activity against bacterial motility and relatively low toxicity.
BMC COMPLEMENTARY MEDICINE AND THERAPIES
(2021)
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)