The plant-derived naphthoquinone lapachol causes an oxidative stress response in Staphylococcus aureus.

Autor: Linzner N; Freie Universität Berlin, Institute of Biology-Microbiology, 14195, Berlin, Germany., Fritsch VN; Freie Universität Berlin, Institute of Biology-Microbiology, 14195, Berlin, Germany., Busche T; Freie Universität Berlin, Institute of Biology-Microbiology, 14195, Berlin, Germany; Center for Biotechnology, University Bielefeld, 33615, Bielefeld, Germany., Tung QN; Freie Universität Berlin, Institute of Biology-Microbiology, 14195, Berlin, Germany., Loi VV; Freie Universität Berlin, Institute of Biology-Microbiology, 14195, Berlin, Germany., Bernhardt J; Institute for Microbiology, University of Greifswald, 17489, Greifswald, Germany., Kalinowski J; Center for Biotechnology, University Bielefeld, 33615, Bielefeld, Germany., Antelmann H; Freie Universität Berlin, Institute of Biology-Microbiology, 14195, Berlin, Germany. Electronic address: haike.antelmann@fu-berlin.de.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2020 Oct; Vol. 158, pp. 126-136. Date of Electronic Publication: 2020 Jul 24.
DOI: 10.1016/j.freeradbiomed.2020.07.025
Abstrakt: Staphylococcus aureus is a major human pathogen, which causes life-threatening systemic and chronic infections and rapidly acquires resistance to multiple antibiotics. Thus, new antimicrobial compounds are required to combat infections with drug resistant S. aureus isolates. The 2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone lapachol was previously shown to exert antimicrobial effects. In this study, we investigated the antimicrobial mode of action of lapachol in S. aureus using RNAseq transcriptomics, redox biosensor measurements, S-bacillithiolation assays and phenotype analyses of mutants. In the RNA-seq transcriptome, lapachol caused an oxidative and quinone stress response as well as protein damage as revealed by induction of the PerR, HypR, QsrR, MhqR, CtsR and HrcA regulons. Lapachol treatment further resulted in up-regulation of the SigB and GraRS regulons, which is indicative for cell wall and general stress responses. The redox-cycling mode of action of lapachol was supported by an elevated bacillithiol (BSH) redox potential (E BSH ), higher endogenous ROS levels, a faster H 2 O 2 detoxification capacity and increased thiol-oxidation of GapDH and the HypR repressor in vivo. The ROS scavenger N-acetyl cysteine and microaerophilic growth conditions improved the survival of lapachol-treated S. aureus cells. Phenotype analyses revealed an involvement of the catalase KatA and the Brx/BSH/YpdA pathway in protection against lapachol-induced ROS-formation in S. aureus. However, no evidence for irreversible protein alkylation and aggregation was found in lapachol-treated S. aureus cells. Thus, the antimicrobial mode of action of lapachol in S. aureus is mainly caused by ROS formation resulting in an oxidative stress response, an oxidative shift of the E BSH and increased protein thiol-oxidation. As ROS-generating compound, lapachol is an attractive alternative antimicrobial to combat multi-resistant S. aureus isolates.
(Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: