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1.
PLoS Comput Biol ; 20(1): e1011749, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38190400

RESUMO

An important mechanical property of cells is their membrane bending modulus, κ. Here, we introduce MEDUSA (MEmbrane DiffUse Scattering Analysis), a cloud-based analysis tool to determine the bending modulus, κ, from the analysis of X-ray diffuse scattering. MEDUSA uses GPU (graphics processing unit) accelerated hardware and a parallelized algorithm to run the calculations efficiently in a few seconds. MEDUSA's graphical user interface allows the user to upload 2-dimensional data collected from different sources, perform background subtraction and distortion corrections, select regions of interest, run the fitting procedure and output the fitted parameters, the membranes' bending modulus κ, and compressional modulus B.


Assuntos
Algoritmos , Computação em Nuvem , Raios X , Radiografia
2.
J Nanobiotechnology ; 22(1): 161, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589895

RESUMO

Antibiotic resistance has garnered significant attention due to the scarcity of new antibiotics in development. Protoporphyrin IX (PpIX)-mediated photodynamic therapy shows promise as a novel antibacterial strategy, serving as an alternative to antibiotics. However, the poor solubility of PpIX and its tendency to aggregate greatly hinder its photodynamic efficacy. In this study, we demonstrate that alkylated EDTA derivatives (aEDTA), particularly C14-EDTA, can enhance the solubility of PpIX by facilitating its dispersion in aqueous solutions. The combination of C14-EDTA and PpIX exhibits potent antibacterial activity against Staphylococcus aureus (S. aureus) when exposed to LED light irradiation. Furthermore, this combination effectively eradicates S. aureus biofilms, which are known to be strongly resistant to antibiotics, and demonstrates high therapeutic efficacy in an animal model of infected ulcers. Mechanistic studies reveal that C14-EDTA can disrupt PpIX crystallization, increase bacterial membrane permeability and sequester divalent cations, thereby improving the accumulation of PpIX in bacteria. This, in turn, enhances reactive oxygen species (ROS) production and the antibacterial photodynamic activity. Overall, this effective strategy holds great promise in combating antibiotic-resistant strains.


Assuntos
Fotoquimioterapia , Staphylococcus aureus , Animais , Protoporfirinas/farmacologia , Ácido Edético/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química
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