Efficacy of outer membrane permeabilization in promoting aromatic isothiocyanates-mediated eradication of multidrug resistant Gram-negative bacteria and bacterial persisters.

Autor: Lo CC; Department of Internal Medicine, Pingtung Veterans General Hospital Longquan Branch, Pingtung, 912012, Taiwan., Yeh TH; Department of Pathology and Laboratory Medicine, Pingtung Veterans General Hospital, Pingtung, 900053, Taiwan., Jao YH; Department of Clinical Laboratory, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, 802511, Taiwan., Wang TH; Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, 813414, Taiwan., Lo HR; Department of Medical Laboratory Science and Biotechnology, Fooyin University, Kaohsiung, 831301, Taiwan. mt096@fy.edu.tw.
Jazyk: angličtina
Zdroj: Folia microbiologica [Folia Microbiol (Praha)] 2024 Oct; Vol. 69 (5), pp. 993-1002. Date of Electronic Publication: 2024 Feb 06.
DOI: 10.1007/s12223-024-01143-6
Abstrakt: 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.
(© 2024. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)
Databáze: MEDLINE
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