Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The problem of antibiotic resistance has prompted the search for new antibiotics with novel mechanisms of action. Analogues of the A54556 cyclic acyldepsipeptides (ADEPs) represent an attractive class of antimicrobial agents that act through dysregulation of caseinolytic protease (ClpP). Previous studies have shown that ADEPs are active against Gram-positive bacteria (e.g., MRSA, VRE, PRSP (penicillin-resistant Streptococcus pneumoniae)); however, there are currently few studies examining Gram-negative bacteria. In this study, the synthesis and biological evaluation of 14 novel ADEPs against a variety of pathogenic Gram-negative and Gram-positive organisms is outlined. Optimization of the macrocyclic core residues and N-acyl side chain culminated in the development of 26, which shows potent activity against the Gram-negative species Neisseria meningitidis and Neisseria gonorrheae and improved activity against the Gram-positive organisms Staphylococcus aureus and Enterococcus faecalis in comparison with known analogues. In addition, the co-crystal structure of an ADEP-ClpP complex derived from N. meningitidis was solved.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.jmedchem.5b01451 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Background: Actinomyces graevenitzii is a relatively uncommon Actinomyces species, which is an oral species and predominantly recovered from respiratory locations [1,2]. It is a gram-positive anaerobic bacteria or microaerobic filamentation bacteria, which can induce pyogenic and granulomatous inflammation characterized by swelling and concomitant pus, sinus formation, and the formation of yellow sulfur granules. All tissues and organs can be infected; the most common type involves the neck and face (55%), followed by the abdominal and pelvic cavities (20%).
View Article and Find Full Text PDFPhosphorylated Derivatives of Quaternary Ammonium Salts: Synthesis, X-Ray Crystal Structure, Antimicrobial Activity and Ecotoxicity.
Curr Microbiol
September 2025
Laboratory for Structural Analysis of Biomacromolecules, Kazan Scientific Center of Russian Academy of Science, Kazan, Russia.
Phosphorylated structural analogs of Benzalkonium Chloride-diisopropoxyphosphorylmethane (dimethyldodecylammonium) bromide 1 (phosphorylated quaternary ammonium salt) and isopropoxyphosphorylmethane (dimethylalkylammonium) 2 (phosphorylated betaine) were synthesized. The structure of compound 1 was confirmed by single crystal X-ray diffraction study. The antibacterial, antifungal, and ecotoxicological profiles of the synthesized compounds were evaluated against aquatic organisms and flowering plants.
View Article and Find Full Text PDFAssessing the prevalence of antimicrobial resistance among pediatric patients at Kamuzu Central Hospital, Malawi.
J Infect Dev Ctries
August 2025
Division of Epidemiology and Biostatistics, Global Health Department, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Introduction: Severe bacterial infections cause significant disease burden in developing countries, including Malawi. The situation is compounded by the scarcity of resources, inconsistent availability of antibiotics, and increasing antimicrobial resistance (AMR).
Methodology: This was a descriptive retrospective study where we analyzed blood culture results of pediatric patients admitted to Kamuzu Central Hospital (KCH), Lilongwe, Malawi.
Biodistribution and dosimetry of Zirconium-labeled microbiota transplants in the pig gut.
Med Phys
September 2025
Imaging Program, Lawson Research Institute, London, Canada.
Background: The gastrointestinal (GI) microbiota, composed of diverse microbial communities, is essential for physiological processes, including immune modulation. Strains such as Escherichia coli Nissle 1917 support gut health by reducing inflammation and resisting pathogens. Microbial therapies using such strains may restore GI balance and offer alternatives to antibiotics, whose overuse contributes to antibiotic resistance.
View Article and Find Full Text PDFBeyond neutropenia: 14 years analysis of bloodstream infections in hematological malignancies.
J Infect Public Health
September 2025
Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address:
Background: Bloodstream infections (BSIs) are a major cause of morbidity and mortality in patients with hematological malignancies (HMs).
Methods: This 14-year retrospective study was conducted at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, from 2007 to 2021. It examined the epidemiological profile, microbial spectrum, resistance patterns, and outcomes of BSIs in HM patients.