Multidrug resistant (MDR) bacteria are recognized to be one of the most important problems in public health. The outer membrane permeability is a critical intrinsic mechanism of bacterial resistance. In addition, bacteria produce a small number of dormant persister cells causing multidrug tolerance that reduces antimicrobial efficacy. This study aimed to evaluate the inhibitory effects of the combination of aromatic isothiocyanates (ITCs) with membrane-active agents on bacterial persisters and MDR Gram-negative bacteria. Our study demonstrated that membrane-active agents, particularly ethylenediaminetetraacetic acid (EDTA) synergistically enhanced the inhibitory activity of aromatic benzyl ITC and phenethyl ITC against most Gram-negative bacteria strains with fractional inhibitory concentration index values ranging from 0.18 to 0.5 and 0.16 to 0.5, respectively, and contributed to an 8- to 64-fold minimal inhibitory concentration reduction compared with those of aromatic ITCs alone. The EDTA-aromatic ITCs combination effectively reduced the survival rates of tested bacteria and significantly eradicated bacterial persisters (p = 0.033 and 0.037, respectively). The growth kinetics analysis also supported the enhanced inhibitory effect of EDTA-aromatic ITCs combination against tested bacteria. Our results suggested an alternate treatment strategy against Gram-negative bacteria, promoting the entry of aromatic ITCs into bacterial cytoplasm to facilitate bacterial clearance and thus preventing the development of bacterial resistance.

• Klíčová slova
• Antimicrobial resistance, Isothiocyanates, Outer membrane permeability, Persistence, Synergy,
• MeSH
• antibakteriální látky * farmakologie   MeSH
• EDTA * farmakologie   MeSH
• gramnegativní bakterie * účinky léků   MeSH
• isothiokyanatany * farmakologie   MeSH
• mikrobiální testy citlivosti * MeSH
• mikrobiální viabilita účinky léků   MeSH
• mnohočetná bakteriální léková rezistence * účinky léků   MeSH
• permeabilita buněčné membrány účinky léků   MeSH
• synergismus léků MeSH
• vnější bakteriální membrána účinky léků   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky * MeSH
• EDTA * MeSH
• isothiokyanatany * MeSH

Several known outer membrane permeabilizers increased susceptibility of a highly resistant pathogenic strain Pseudomonas aeruginosa to different antibiotics and plant extracts. Of all the chemicals tested, EDTA, sodium citrate and sodium hexametaphosphate (HMP) were found to be potent permeabilizers as shown by enhanced lysis of the bacteria in the presence of lysozyme. In the presence of EDTA and sodium citrate susceptibility of the strain to gentamicin and rifampicin increased markedly. The strain was resistant to vancomycin but became susceptible when grown in the presence of increasing amounts of EDTA and sodium citrate. Similar results were obtained for erythromycin when treated with sodium citrate. EDTA was found to be most potent permeabilizer in enhancing the activity of the plant extracts. Though HMP was an effective permeabilizer it had a weak or no effect on the activity of the antibiotics and plant extracts.

• MeSH
• antibakteriální látky farmakologie   MeSH
• bakteriální léková rezistence MeSH
• citráty farmakologie   MeSH
• citronan sodný MeSH
• EDTA farmakologie   MeSH
• erythromycin farmakologie   MeSH
• fosfáty farmakologie   MeSH
• gentamiciny farmakologie   MeSH
• muramidasa farmakologie   MeSH
• permeabilita buněčné membrány účinky léků   MeSH
• Pseudomonas aeruginosa účinky léků   MeSH
• rifampin farmakologie   MeSH
• rostlinné extrakty farmakologie   MeSH
• vankomycin farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• citráty MeSH
• citronan sodný MeSH
• EDTA MeSH
• erythromycin MeSH
• fosfáty MeSH
• gentamiciny MeSH
• muramidasa MeSH
• rifampin MeSH
• rostlinné extrakty MeSH
• sodium polymetaphosphate MeSH Prohlížeč
• vankomycin MeSH