Anti-virulence and bactericidal activities of Stattic against Shigella sonnei

Abstract

ABSTRACT Shigella sonnei is an important human pathogen that provokes severe colitis and diarrhea, causing high mortality and morbidity worldwide. Because of increasing drug resistance, it is particularly important to develop new antibacterial agents against S. sonnei . In this study, we report that Stattic, a potent signal transducer and activator of transcription 3 inhibitor, was found to be effective against S. sonnei . Our results showed that Stattic has dual antibacterial mechanisms. At low concentrations, Stattic binds to GalU of S. sonnei , inhibits its enzyme activity, and then reduces biofilm formation and extracellular polysaccharide production, which ultimately attenuates S. sonnei virulence in human cell lines. At high concentrations, Stattic could kill bacteria by disrupting the integrity of the bacterial cell membrane, causing space collapse and the outflow of contents. Furthermore, Stattic showed excellent synergistic effects with antibiotics against S. sonnei . In addition, Stattic also showed anti-virulence activity against Escherichia coli and Klebsiella pneumoniae . Together, our findings suggest the promising potential and advantages of Stattic as a new therapeutic agent against bacterial pathogens. IMPORTANCE Shigella sonnei is a major human enteric pathogen that causes bacillary dysentery. The increasing spread of drug-resistant S. sonnei strains has caused an emergent need for the development of new antimicrobial agents against this pathogenic bacterium. In this study, we demonstrate that Stattic employs two antibacterial mechanisms against S. sonnei . It exerted both anti-virulence activity and bactericidal activity against S. sonnei , suggesting that it shows advantages over traditional antibiotics. Moreover, Stattic showed excellent synergistic effects with kanamycin, ampicillin, chloramphenicol, and gentamicin against S. sonnei . Our findings suggest that Stattic has promising potential for development as a new antibiotic or as an adjuvant to antibiotics for infections caused by S. sonnei .