Small-Molecule Compound CY-158-11 Inhibits Staphylococcus aureus Biofilm Formation

Li Shen; Jiao Zhang; Yao Chen; Lulin Rao; Xinyi Wang; Huilin Zhao; Bingjie Wang; Yanghua Xiao; Jingyi Yu; Yanlei Xu; Junhong Shi; Weihua Han; Zengqiang Song; Fangyou Yu

doi:10.1128/spectrum.00045-23

Microbiology Spectrum (Jun 2023)

Small-Molecule Compound CY-158-11 Inhibits Staphylococcus aureus Biofilm Formation

Li Shen,
Jiao Zhang,
Yao Chen,
Lulin Rao,
Xinyi Wang,
Huilin Zhao,
Bingjie Wang,
Yanghua Xiao,
Jingyi Yu,
Yanlei Xu,
Junhong Shi,
Weihua Han,
Zengqiang Song,
Fangyou Yu

Affiliations

Li Shen: Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
Jiao Zhang: Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
Yao Chen: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
Lulin Rao: Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
Xinyi Wang: Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
Huilin Zhao: Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
Bingjie Wang: Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
Yanghua Xiao: Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
Jingyi Yu: Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
Yanlei Xu: Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
Junhong Shi: Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
Weihua Han: Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
Zengqiang Song: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
Fangyou Yu: Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China

DOI: https://doi.org/10.1128/spectrum.00045-23
Journal volume & issue: Vol. 11, no. 3

Abstract

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ABSTRACT Staphylococcus aureus is an important human pathogen and brings about many community-acquired, hospital-acquired, and biofilm-associated infections worldwide. It tends to form biofilms, triggering the release of toxins and initiating resistance mechanisms. As a result of the development of S. aureus tolerance to antibiotics, there are few drugs can availably control biofilm-associated infections. In this study, we synthesized a novel small-molecule compound CY-158-11 (C22H14Cl2NO2Se2) and proved its inhibitory effect on the biofilm formation of S. aureus at a subinhibitory concentration (1/8 MIC). The subinhibitory concentration of CY-158-11 not only did not affect the growth of bacteria but also had no toxicity to A549 cells or G. mellonella. Total biofilm biomass was investigated by crystal violet staining, and the results were confirmed by SYTO 9 and PI staining through confocal laser scanning microscopy. Moreover, CY-158-11 effectively prevented initial attachment and repressed the production of PIA instead of autolysis. RT-qPCR analysis also exhibited significant suppression of the genes involved in biofilm formation. Taken together, CY-158-11 exerted its inhibitory effects against the biofilm formation in S. aureus by inhibiting cell adhesion and the expression of icaA related to PIA production. IMPORTANCE Most bacteria exist in the form of biofilms, often strongly adherent to various surfaces, causing bacterial resistance and chronic infections. In general, antibacterial drugs are not effective against biofilms. The small-molecule compound CY-158-11 inhibited the biofilm formation of S. aureus at a subinhibitory concentration. By hindering adhesion and PIA-mediated biofilm formation, CY-158-11 exhibits antibiofilm activity toward S. aureus. These findings point to a novel therapeutic agent for combating intractable S. aureus-biofilm-related infections.

Published in Microbiology Spectrum

ISSN: 2165-0497 (Online)
Publisher: American Society for Microbiology
Country of publisher: United States
LCC subjects: Science: Microbiology
Website: https://journals.asm.org/journal/spectrum

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