Geraniol as a novel antivirulence agent against bacillary dysentery-causing Shigella sonnei

Bacillary dysentery remains one of the most important diarrhoeal diseases affecting humans in the 21st century particularly in resource-poor nations. The etiological agents of this disease, Shigella bacteria, derive from diverse origins of Escherichia coli. Shigella sonnei is the causative agent for the current bacillary dysentery pandemic in many of the newly industrialised countries across all continents and has replaced Shigella flexneri, once the most prevalent species globally. Contemporary epidemic S. sonnei strains mostly belong to the lineage III and exhibit multiple drug resistance due to the spread of transposons and independent point mutations in the gyrase gene. In addition to that, developing an effective vaccine against Shigella remains a challenge. Hence, it has become urgent to seek alternative approaches to treat Shigella infection. Here, we show that geraniol, a natural substance present in the essential oils of plants such as rose and lemongrass can reduce S. sonnei proliferation inside host cells and protect Galleria mellonella larvae from killing by S. sonnei infection. We present evidence that geraniol competitively inhibits the catalytic activity of the master virulence regulator, DsbA, a periplasmic disulphide bond oxidoreductase required for Shigella survival in the host cell cytosol.