Fusaric acid modulates Type Three Secretion System of Salmonella enterica serovar Typhimurium.
Natural small-molecule products are promising lead compounds for developing a generation of novel antimicrobials agents to meet the challenge of antibiotic-resistant pathogens. To facilitate the search for novel anti-virulence agents, we chose a virulence factor of Type Three Secretion System (T3SS) as a drug target to screen candidates from a small-molecule library in our laboratory. This study demonstrated fusaric acid had dramatically inhibitory effects on secretion of Salmonella island 1 (SPI-1) effector proteins and invasion of Salmonella into HeLa cells. Moreover, fusaric acid had no inhibitory effects on bacterial growth and viability of host cells. Protein HilA is a key regulator of SPI-1 in Salmonella, which affects transcription of SPI-1 effectors and SPI-1 apparatus genes. In this study, fusaric acid (FA) did not affect secretion of SPI-1 effectors in HilA over-expressed strain, suggesting it did not affect the transcription of SPI-1. In addition, fusaric acid did not affect the protein level of apparatus protein PrgH in SPI-1 needle complex. As a result, we proposed fusaric acid had an inhibitory effect on SPI-1 probably depending on its influence on SicA/InvF. In summary, fusaric acid is a novel inhibitor of T3SS with potential for further developing novel anti-virulence agents.
School of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan 250355, China; Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
Jianfang
J
Li
School of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
Weiyang
W
Sun
Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
Zhixing
Z
Guo
Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
Chunhua
C
Lu
Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China. Electronic address: yshen@sdu.edu.cn.
Yuemao
Y
Shen
D001426:Bacterial Proteins / Q000187:drug effects*; D058947:Bacterial Secretion Systems / Q000187:drug effects* / Q000502:physiology; D005669:Fusaric Acid / Q000494:pharmacology*; D006367:HeLa Cells / Q000382:microbiology; D006801:Humans; D012480:Salmonella Infections / Q000188:drug therapy; D012486:Salmonella typhimurium / Q000472:pathogenicity*; D037521:Virulence Factors / Q000037:antagonists & inhibitors*
D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D037521:Virulence Factors; D005669:Fusaric Acid
Fusaric acid; Inhibitor; Salmonella enterica serovar Typhimurium; Type Three Secretion System