A HigB-like toxin induces non-replicating Salmonella inside macrophages by inhibiting RNase III-dependent rRNA maturation [sehB_RNA-Seq]

Many bacteria are often resistant to antibiotic treatment and drugs because, even if these drugs are effective, bacteria can slow down their growth rate and thus attenuate the effectiveness of the drug. A similar growth-rate control is detected in pathogenic bacteria that infect and persist inside their hosts. The bacterial growth rate within host cells can be regulated by multiple signaling pathways, most of which are still unknown. A toxin-antitoxin (TA) system is one of the candidates for controlling bacterial growth because the TA system could slow down growth by expressing a toxin component. The toxin protein can be neutralized by the antitoxin component, serving as a non-heritable phenotypic switch for growth rate. In this study, we investigated a type II toxin-antitoxin system from the intracellular bacterial pathogen Salmonella enterica serovar Typhimurium. We characterized residues required for toxin's activity and a potential mechanism of the toxin by searching for its target via bacterial two-hybrid screening. Understanding the underlying mechanism of toxin-mediated persister formation and growth rate control within host cells will provide a new alternative to treat antibiotic resistant bacteria or intracellular bacteria surviving within host cells. Overall design: We performed an RNA-Seq between the sehB mutant and wild type to analyze how the mRNA profile changed under the influence of overexpressed sehA as a result of sehB deletion.