The malS-5'UTR regulates hisG, a key gene in the histidine biosynthetic pathway in Salmonella enterica serovar Typhi

Bacterial noncoding RNAs (ncRNA) regulate diverse cellular processes, including virulence and environmental fitness. The malS 5' untranslated region (named malS-5'UTR) was identified as a regulatory ncRNA that increases the invasive capacity of Salmonella enterica serovar Typhi. An IntaRNA search suggested base pairing between malS-5'UTR and hisG mRNA, a key gene in the histidine biosynthetic pathway. Overexpression of malS-5'UTR markedly reduced bacterial growth in minimal medium without histidine. Overexpression of malS-5'UTR increased mRNA from his operon genes, independently of the bax gene, and decreased HisG protein in Salmonella Typhi. RNA structure analysis showed base pairing of the malS-5'UTR RNA with the hisG mRNA across the ribosome binding site. Thus, we propose that malS-5'UTR inhibited hisG translation, probably by base pairing to the Shine-Dalgarno sequence.