Beuerman RW
Evaluation of Host Defense Peptide (CaD23)-Antibiotic Interaction and Mechanism of Action: Insights From Experimental and Molecular Dynamics Simulations Studies
Antimicrobial resistance (AMR) is currently one of the major global health threats. (Prestinaci et al., 2015; Ventola, 2015) By 2050, it is estimated to cause 10 million deaths and cost the global economy up to 100 trillion USD if the issue remains untackled. (O’Neill, 2016) In addition, non-systemic infections, including ocular and skin infections, are being increasingly affected by drug-resistant pathogens, which usually result in poor prognosis (Ventola, 2015; Pulido-Cejudo et al., 2017; Ting et al., 2021a). In view of the colossal impact on global health and economy, various initiatives and strategies have been proposed and implemented to tackle AMR. These include establishment of antimicrobial stewardship to monitor the use of antimicrobial agents and the rise of AMR, development of new drugs and vaccines, drug repurposing, and incentivising pharmaceutical companies for investing in antimicrobial drug development. (Ventola, 2015)
ReadIncreased Protein S-Glutathionylation in Leber’s Hereditary Optic Neuropathy (LHON)
Leber’s hereditary optic neuropathy (LHON, MIM#535000) is the most common form of inherited optic neuropathies and mitochondrial DNA-related diseases. The pathogenicity of mutations in genes encoding components of mitochondrial Complex I is well established, but the underlying pathomechanisms of the disease are still unclear. Hypothesizing that oxidative stress related to Complex I deficiency may increase protein S-glutathionylation, we investigated the proteome-wide S-glutathionylation profiles in LHON (n = 11) and control (n = 7) fibroblasts, using the GluICAT platform that we recently developed. Glutathionylation was also studied in healthy fibroblasts (n = 6) after experimental Complex I inhibition. The significantly increased reactive oxygen species (ROS) production in the LHON group by Complex I was shown experimentally.
ReadConformational Transitions of Melittin between Aqueous and Lipid Phases: Comparison of Simulations with Experiments
Peptides are promising drug candidates with advantageous therapeutic properties. However, their inherent flexibility makes the development of structure−activity relationships difficult. Molecular dynamics simulations have been widely used to study peptide conformations, but they are limited by force field parameters.
ReadAntimicrobial activity profiles of Amphiphilic Xanthone derivatives are a function of their molecular Oligomerization
Currently, membrane-targeting small antimicrobial peptidomimetics (SAP) are important in antibiotic development because bacteria appear to develop resistance to these surface-active compounds less readily. However, the molecular membrane-targeting action of SAPs has received little attention. In this study, we investigated the effect of oligomerization of amphiphilic xanthone, a model SAP, on its antimicrobial properties against both Gram-positive and Gram-negative bacteria.
ReadMolecular insights into the membrane affinities of model hydrophobes
embrane-active antibiotics are of great interest in fighting bacterial resistance. α-Mangostin is a membrane-active molecule, but there are no details of its mechanism of action at the atomistic level.
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