The usnic acid derivative peziculone targets cell walls of Gram-positive bacteria revealed by high-throughput CRISPRi-seq analysis

Zhang，Han1,2,3; Li，Xiaojie1; Liu，Xue4; Ji，Xia1; Ma，Xuan5; Chen，Jun3; Bao，Yanmin6; Zhang，Yingdan2,3; Xu，Liangxiong1; Yang，Liang2,3; Wei，Xiaoyi7

2023-09-01

10.1016/j.ijantimicag.2023.106876

International Journal of Antimicrobial Agents   Impact Factor & Quartile

0924-8579

1872-7913

Usnic acid, a representative dibenzofuran metabolite, is known to have antimicrobial properties. However, despite considerable interest as an antimicrobial agent, the mechanism by which usnic acid and its derivatives exert their action is not fully characterized. This article describes the synthesis of peziculone, a 5:1 equilibrium mixture of two inseparable usnic acid derivatives: peziculone A and peziculone B. The antibacterial activity of peziculone against several Gram-positive bacterial pathogens was found to be significantly better compared with usnic acid. Clustered regularly interspaced short palindromic repeats interference sequencing analysis and membrane fluorescent staining were used to demonstrate that peziculone destabilizes the cell walls of Gram-positive bacteria. Additionally, peziculone 2.5 and 3.5 µg/mL impaired cell surface appendages and biofilm formation by Staphylococcus aureus. Taken together, these data demonstrate that peziculone, a derivative compound of usnic acid, has significant antimicrobial activity against Gram-positive bacteria by targeting the cell walls; this provides a platform for development of novel antibacterial drugs.

Antimicrobials CRISPRi-seq Dibenzofuran Pezicula neosporulosa Peziculone Usnic acid

SCI

English

Others

Guangdong Natural Science Foundation for Distinguished Young Scholar[2020B1515020 0 03] ; Guangdong Pearl -River Talent Plan Expert Program[2019QN01Y163] ; Science and Technology Program of Shenzhen[2020N099] ; National Nature Science Foundation of China (NSFC )[31772032] ; NSFC["82270012","32200155","32270196"] ; Shenzhen Science and Technology Program[KQTD20200909113758004]

Infectious Diseases ; Microbiology ; Pharmacology & Pharmacy

Infectious Diseases ; Microbiology ; Pharmacology & Pharmacy

WOS:001048734800001

ELSEVIER

PHARMACOLOGY & TOXICOLOGY

2-s2.0-85165116039

Scopus

1.School of Life Sciences,Huizhou University,Huizhou,China
2.School of Medicine,Southern University of Science and Technology,Shenzhen,Guangdong,China
3.Shenzhen Third People's Hospital,National Clinical Research Centre for Infectious Disease,The Second Affiliated Hospital of Southern University of Science and Technology,Shenzhen,China
4.Department of Pathogen Biology,Base for International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Centre,International Cancer Centre,Shenzhen University Health Science Centre,Shenzhen,China
5.South China Sea Institute of Oceanology,Chinese Academy of Sciences,Guangzhou,China
6.Department of Respiratory Diseases,Shenzhen Children's Hospital,Shenzhen,Guangdong,China
7.Key Laboratory of South China Agricultural Plant Molecular Analysis and Genetic Improvement / Guangdong Provincial Key Laboratory of Digital Botanical Garden and Public Science,South China Botanical Garden,Chinese Academy of Sciences,Guangzhou,China

Zhang，Han,Li，Xiaojie,Liu，Xue,et al. The usnic acid derivative peziculone targets cell walls of Gram-positive bacteria revealed by high-throughput CRISPRi-seq analysis[J]. International Journal of Antimicrobial Agents,2023,62(3).

Zhang，Han.,Li，Xiaojie.,Liu，Xue.,Ji，Xia.,Ma，Xuan.,...&Wei，Xiaoyi.(2023).The usnic acid derivative peziculone targets cell walls of Gram-positive bacteria revealed by high-throughput CRISPRi-seq analysis.International Journal of Antimicrobial Agents,62(3).

Zhang，Han,et al."The usnic acid derivative peziculone targets cell walls of Gram-positive bacteria revealed by high-throughput CRISPRi-seq analysis".International Journal of Antimicrobial Agents 62.3(2023).