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Chemoproteomic Study of Effect of Halogenated Hydroxynaphthalene-carboxanilides on Staphylococcus aureus.
Autoři | |
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Rok publikování | 2024 |
Druh | Článek ve sborníku |
Fakulta / Pracoviště MU | |
Citace | |
www | https://www.mdpi.com/2673-4583/16/1/15/pdf |
Doi | http://dx.doi.org/10.3390/ecsoc-28-20152 |
Klíčová slova | hydroxynaphthalenecarboxanilides; Staphylococcus aureus; ABPP; chemoproteomics; HPLC-MS/MS |
Popis | Recently reportedmultihalogenated (CF3/Cl) anilides of 1-hydroxynaphthalene-2-carboxanilides showed significant activity against both the reference strain Staphylococcus aureus ATCC 29213 and clinical isolates of methicillin-resistant S. aureus (MRSA). This fact inspired further investigation of the effect of these compounds on staphylococci. Chemoproteomics is a tool for investigating protein targets of potential drugs. It makes it possible to understand the effect of a bioactive molecule on a living system. An activity-based protein profiling (ABPP) method was employed using highly active and inactive ring-substituted 1-hydroxynaphthalene-2-carboxanilides as probes. The experiment was performed on the universally sensitive collection strain S. aureus ATCC 29213. Tryptic cleavage of proteins was performed prior to HPLC-MS/MS analysis. Protein profiles of control samples (S. aureus cells) and profiles of S. aureus treated with inactive/active derivatives were investigated and compared to one another. More than 1000 proteins were analyzed, with approximately 70% of the proteins increased and 30% of the proteins decreased after treatment with the investigated compounds. Treatment with the inactive compound mainly resulted in the expression of various proteins, so it can be assumed that the changes in the protein profile did not affect the basic biochemical pathways or that the microorganism was able to adapt by activating other pathways/expressing other proteins, surviving. Treatment with the highly active agent resulted in much smaller proteomic changes (mainly, the inhibition of several proteins compared to the inactive compound), and S. aureus failed to adapt and was killed. |