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Efficacy of outer membrane permeabilization in promoting aromatic isothiocyanates-mediated eradication of multidrug resistant Gram-negative bacteria and bacterial persisters
CC. Lo, TH. Yeh, YH. Jao, TH. Wang, HR. Lo
Status minimal Language English Country Czech Republic
Document type Journal Article
Grant support
MOST 111-2637-B-242-001
National Science and Technology Council
VHLC-11108
Pingtung Veterans General Hospital (TW)
VHLC-11115
Pingtung Veterans General Hospital
- MeSH
- Anti-Bacterial Agents * pharmacology MeSH
- Edetic Acid * pharmacology MeSH
- Gram-Negative Bacteria * drug effects MeSH
- Isothiocyanates * pharmacology MeSH
- Microbial Sensitivity Tests * MeSH
- Microbial Viability drug effects MeSH
- Drug Resistance, Multiple, Bacterial * drug effects MeSH
- Cell Membrane Permeability drug effects MeSH
- Drug Synergism MeSH
- Bacterial Outer Membrane drug effects MeSH
- Publication type
- Journal Article MeSH
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.
Department of Clinical Laboratory Kaohsiung Municipal Min Sheng Hospital Kaohsiung 802511 Taiwan
Department of Medical Laboratory Science and Biotechnology Fooyin University Kaohsiung 831301 Taiwan
References provided by Crossref.org
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