A fluoroquinolone-sensitive Shigella sonnei UKMCC1015 downregulates the expression of ribosomal proteins in response to sub-lethal concentration of norfloxacin

Shigella spp. commonly causes gastroenteritis known as shigellosis, and severe cases require antibiotic treatments. However, the increased presence of antibiotics in the environment in recent years can lead to antibiotic resistance. Sub-lethal antibiotic concentrations can promote resistance, but its effect on sensitive bacteria prior to resistance development is unknown.

In this study, the complete genome of Shigella sonnei UKMCC1015, a sensitive strain from Malaysia is presented. Subsequently, the transcriptomic response of this strain towards sub-MIC levels of norfloxacin, a commonly used fluoroquinolone is investigated. This study reveals that the expressions of the antimicrobial resistance genes and antibiotic targets (DNA gyrase and topoisomerase IV) are not affected. Interestingly, multiple ribosomal protein operons were downregulated while a small regulatory RNA (sRNA), GcvB was upregulated in response to constant exposure to sub-MIC norfloxacin.

To our knowledge, association between sub-lethal fluoroquinolone and expression of ribosomal protein operons as well as GcvB sRNA have never been reported. Collectively, these findings suggest that there are novel pathways possibly related to ppGpp levels that are involved in the adaptive response of S. sonnei towards fluoroquinolones.