AUTHOR=Shi Yunjia , Chen Xindi , Shu Jingyan , Liu Yang , Zhang Yong , Lv Qianghua , Wang Jianfeng , Deng Xuming , Liu Hongtao , Qiu Jiazhang 

TITLE=Harmine, an inhibitor of the type III secretion system of Salmonella enterica serovar Typhimurium

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.967149

DOI=10.3389/fcimb.2022.967149

ISSN=2235-2988

ABSTRACT=<p>New therapeutic strategies for clinical <italic>Salmonella enterica</italic> serovar Typhimurium (<italic>S.</italic> Typhimurium) infection are urgently needed due to the generation of antibiotic-resistant bacteria. Inhibition of bacterial virulence has been increasingly regarded as a potential and innovative strategy for the development of anti-infection drugs. <italic>Salmonella</italic> pathogenicity island (SPI)-encoded type III secretion system (T3SS) represents a key virulence factor in <italic>S.</italic> Typhimurium, and active invasion and replication in host cells is facilitated by the secretion of T3SS effector proteins. In this study, we found that harmine could inhibit T3SS secretion; thus, its potential anti-<italic>S</italic>. Typhimurium infection activity was elucidated. Harmine inhibits the secretion and expression of T3SS effector proteins and consequently attenuates the <italic>S.</italic> Typhimurium invasion function of HeLa cells. This inhibition may be implemented by reducing the transcription of pathogenesis-related SPI-1 transcriptional activator genes <italic>hilD</italic>, <italic>hilC</italic>, and <italic>rtsA</italic>. Harmine improves the survival rate and bacterial loads of mice infected with <italic>S</italic>. Typhimurium. In summary, harmine, an effective T3SS inhibitor, could be a leading compound for the development of treatments for <italic>Salmonella</italic> infection.</p>