Academic Journal
Insights into the Mechanism of Action of Bactericidal Lipophosphonoxins.
| العنوان: | Insights into the Mechanism of Action of Bactericidal Lipophosphonoxins. |
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| المؤلفون: | Natalya Panova, Eva Zborníková, Ondřej Šimák, Radek Pohl, Milan Kolář, Kateřina Bogdanová, Renata Večeřová, Gabriela Seydlová, Radovan Fišer, Romana Hadravová, Hana Šanderová, Dragana Vítovská, Michaela Šiková, Tomáš Látal, Petra Lovecká, Ivan Barvík, Libor Krásný, Dominik Rejman |
| المصدر: | PLoS ONE, Vol 10, Iss 12, p e0145918 (2015) |
| بيانات النشر: | Public Library of Science (PLoS), 2015. |
| سنة النشر: | 2015 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | The advantages offered by established antibiotics in the treatment of infectious diseases are endangered due to the increase in the number of antibiotic-resistant bacterial strains. This leads to a need for new antibacterial compounds. Recently, we discovered a series of compounds termed lipophosphonoxins (LPPOs) that exhibit selective cytotoxicity towards Gram-positive bacteria that include pathogens and resistant strains. For further development of these compounds, it was necessary to identify the mechanism of their action and characterize their interaction with eukaryotic cells/organisms in more detail. Here, we show that at their bactericidal concentrations LPPOs localize to the plasmatic membrane in bacteria but not in eukaryotes. In an in vitro system we demonstrate that LPPOs create pores in the membrane. This provides an explanation of their action in vivo where they cause serious damage of the cellular membrane, efflux of the cytosol, and cell disintegration. Further, we show that (i) LPPOs are not genotoxic as determined by the Ames test, (ii) do not cross a monolayer of Caco-2 cells, suggesting they are unable of transepithelial transport, (iii) are well tolerated by living mice when administered orally but not peritoneally, and (iv) are stable at low pH, indicating they could survive the acidic environment in the stomach. Finally, using one of the most potent LPPOs, we attempted and failed to select resistant strains against this compound while we were able to readily select resistant strains against a known antibiotic, rifampicin. In summary, LPPOs represent a new class of compounds with a potential for development as antibacterial agents for topical applications and perhaps also for treatment of gastrointestinal infections. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1932-6203 |
| Relation: | http://europepmc.org/articles/PMC4696656?pdf=render; https://doaj.org/toc/1932-6203 |
| DOI: | 10.1371/journal.pone.0145918 |
| URL الوصول: | https://doaj.org/article/645b79dd6ac04f01b3677db66966ded9 |
| رقم الانضمام: | edsdoj.645b79dd6ac04f01b3677db66966ded9 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0145918 |