Current Issue : July - September Volume : 2019 Issue Number : 3 Articles : 5 Articles
This study compared the activity of cefepime + zidebactam (FEP-ZID) and selected\ncurrently available antibacterial agents against a panel of multidrug-resistant (MDR) clinical isolates\nchosen to provide an extreme challenge for antibacterial activity. FEPâ??ZID had a very broad\nand potent in vitro spectrum of activity, and was highly active against many MDR isolates of\nEnterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii. Notably, it inhibited isolates\nproducing carbapenemases of Ambler classes A, B, and D, and P. aeruginosa isolates with multiple\nresistance mechanisms including combinations of upregulated efflux, diminished or non-functional\nOprD porins, and AmpC overproduction. Its clinical role will be determined initially by the\nbreakpoints assigned to it, comparison studies with other investigational Beta-lactamase inhibitor\ncombinations, and ultimately by the developing body of therapeutic outcome data....
The continued emergence of new antibiotic resistant bacterial strains has resulted in great\ninterest in the development of new antimicrobial treatments. Antimicrobial peptides (AMPs) are\none of many potential classes of molecules to help meet this emerging need. AMPs are naturally\nderived sequences, which act as part of the innate immune system of organisms ranging from insects\nthrough humans. We investigated the antimicrobial peptide AP3, which is originally isolated from\nthe winter flounder Pleuronectes americanus. This peptide is of specific interest because it does not\nexhibit the canonical facially amphiphilic orientation of side chains when in a helical orientation.\nDifferent analogs of AP3 were synthesized in which length, charge identity, and Trp position were\nvaried to investigate the sequence-structure and activity relationship. We performed biophysical and\nmicrobiological characterization using fluorescence spectroscopy, CD spectroscopy, vesicle leakage\nassays, bacterial membrane permeabilization assays, and minimal inhibitory concentration (MIC)\nassays. Fluorescence spectroscopy showed that the peptides bind to lipid bilayers to similar extents,\nwhile CD spectra show the peptides adopt helical conformations. All five peptides tested in this study\nexhibited binding to model lipid membranes, while the truncated peptides showed no measurable\nantimicrobial activity. The most active peptide proved to be the parent peptide AP3 with the highest\ndegree of leakage and bacterial membrane permeabilization. Moreover, it was found that the ability\nto permeabilize model and bacterial membranes correlated most closely with the ability to predict\nantimicrobial activity....
Lagunamide D, a new cytotoxic macrocyclic depsipeptide, was discovered from a collection\nof marine cyanobacteria from Loggerhead Key in the Dry Tortugas, Florida. An intramolecular\nester exchange was observed, where the 26-membered macrocycle could contract to a 24-membered\ncompound via acyl migration at the 1,3-diol unit, and the transformation product was named\nlagunamide Dâ??. The planar structures of both compounds were elucidated using a combination of\nnuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectroscopy (HRMS).\nThe absolute configurations were determined on the basis of enantioselective analysis, modified\nMosherâ??s analysis, Kishi NMR database, and direct comparison with lagunamide A, a structure\nclosely resembling lagunamide D. Lagunamides A and D displayed low-nanomolar antiproliferative\nactivity against A549 human lung adenocarcinoma cells, while the structural transformation from the\n26-membered lagunamide D macrocycle to the 24-membered ring structure for lagunamide Dâ?? led to\na 9.6-fold decrease in activity. Lagunamide D also displayed potent activity in triggering apoptosis\nin a dose- and time-dependent manner. Further investigation on the mechanism of action of the\nlagunamide scaffold is needed to fully explore its therapeutic potential as an anticancer agent....
Parenteral amphotericin B has been considered as first-line therapy in the treatment of\nsystemic fungal and parasitic infections, however its use has been associated with a number of\nlimitations including affordability, accessibility, and an array of systemic toxicities. Until very recently,\nit has been very challenging to develop a bioavailable formulation of amphotericin B due to its\nphysical chemical properties, limited water and lipid solubility, and poor absorption. This perspective\nreviews several novel oral Amphotericin B formulations under development that are attempting to\novercome these limitations....
New medicines for the treatment of bacterial biofilm formation are required. For this\nreason, this study shows the in vitro activity of betulinic acid (BA), ursolic acid (UA) and their twenty\nderivatives against planktonic and biofilm cells (gram-positive bacterial pathogens: Enterococcus\nfaecalis, Staphylococcus aureus and Staphylococcus epidermidis). We evaluated the antibiofilm activity\n(through the crystal violet method), as well as the antibacterial activity via absorbance.......................
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