Molecular Mechanism of Hfq-dependent sRNA1039 and sRNA1600 Regulating Antibiotic Resistance and Virulence in Shigella sonnei

Bacillary dysentery caused by Shigella is a significant concern for human health. The small non-coding RNA (sRNA) plays a crucial role in regulating antibiotic resistance and virulence in Shigella. However, the specific mechanisms behind this phenomenon are still not fully understood. Our study discovered two sRNAs (sRNA1039 and sRNA1600) that may be involved in bacterial resistance and virulence. By constructing deletion mutants (WT/ΔSR1039 and WT/ΔSR1600), we found that the WT/ΔSR1039 mutants caused a 2-fold increase in the sensitivity against ampicillin, gentamicin and cefuroxime, and the WT/ΔSR1600 mutants caused a 2-fold increase in the sensitivity against cefuroxime. Furthermore, the WT/ΔSR1600 mutants caused a decrease in the adhesion and invasion of bacteria to HeLa cells (P < 0.01) and changed the oxidative stress level of bacteria to reduce their survival rate (P < 0.001). Subsequently, we explored the molecular mechanisms how sRNA1039 and sRNA1600 regulate antibiotic resistance and virulence. The deletion of sRNA1039 accelerated the degradation of target gene cfa mRNA and reduced its expression, thereby indirectly and negatively regulating the expression of pore protein gene ompD to increase bacterial sensitivity against ampicillin, gentamicin and cefuroxime. The inactivation of sRNA1600 reduced the formation of persister cells to reduce the resistance against cefuroxime and reduced the expression of Type III secretion system (T3SS) related genes to reduce bacterial virulence by reducing the expression of target gene tomB. These provide new insights into Hfq-sRNA-mRNA regulation of resistance and virulence network of Shigella sonnei, which could potentially promote the development of more effective treatment strategies.