Insights into the Mechanism of Action of Bactericidal Lipophosphonoxins

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F15%3A00456130" target="_blank" >RIV/61388971:_____/15:00456130 - isvavai.cz</a>

Alternative codes found

RIV/61388963:_____/15:00455963 RIV/00216208:11310/15:10316494 RIV/00216208:11320/15:10316494 RIV/61989592:15110/15:33157282 RIV/60461373:22330/15:43900475

Result on the web

<a href="http://dx.doi.org/10.1371/journal.pone.0145918" target="_blank" >http://dx.doi.org/10.1371/journal.pone.0145918</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pone.0145918" target="_blank" >10.1371/journal.pone.0145918</a>

Result language

angličtina

Original language name

Insights into the Mechanism of Action of Bactericidal Lipophosphonoxins

Original language description

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.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CE - Biochemistry

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2015

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

PLoS ONE

ISSN

1932-6203

e-ISSN

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Volume of the periodical

10

Issue of the periodical within the volume

12

Country of publishing house

US - UNITED STATES

Number of pages

28

Pages from-to

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UT code for WoS article

000367510500095

EID of the result in the Scopus database

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