Umeå universitets logga

Bacterial pathogens often employ RNA regulatory elements located in the 5' untranslated regions (UTRs) to control gene expression. Using a comparative structural analysis, we examine the structure of 5' UTRs at a global scale in the pathogenic bacterium Listeria monocytogenes under different conditions. In addition to discovering an RNA thermoswitch and detecting simultaneous interaction of ribosomes and small RNAs with mRNA, we identify structural changes in the 5' UTR of an mRNA encoding the post-translocation chaperone PrsA2 during infection conditions. We demonstrate that the 5' UTR of the prsA2 mRNA base pairs with the 3' UTR of the full-length hly mRNA encoding listeriolysin O, thus preventing RNase J1-mediated degradation of the prsA2 transcript. Mutants lacking the hly-prsA2 interaction exhibit reduced virulence properties. This work highlights an additional level of RNA regulation, where the mRNA encoding a chaperone is stabilized by the mRNA encoding its substrate.

In this issue of Cell Chemical Biology, Wang et al. (2017) examine the effect of the novel synthetic molecule ribocil-C and the natural compound roseoflavin in Gram-positive pathogens. In methicillin-resistant Staphylococcus aureus (MRSA), ribocil-C and roseoflavin target two autonomous riboswitches simultaneously, thereby inhibiting de novo synthesis and uptake of riboflavin.

The emerging development of antibiotic resistant bacteria calls for novel types of antibacterial agents. In this work we examined the putative antibacterial effect of purine analogs in Listeria monocytogenes. We show that, among several tested purine analogs, only 6-N-hydroxylaminopurine (6-N-HAP) reduces the viability of the Gram-positive pathogenListeria monocy-togenes. As in Bacillus subtilis, 6-N-HAP terminates expression at guanine riboswitches in L. monocyto-genes hence preventing expression of their downstream genes. However, we show that the bacteriocidal effect of the compound was unlinked to the terminated expression at the guanine riboswitches. When further examining the antimicrobial effect, we observed that 6-N-HAP acts as a potent mutagen in L. monocytogenes, by increasing the mutation rate and inducing the SOS-response. Also, addition of 6N-HAP decreased virulence gene expression by reducing both the levels and activity of the virulence regulator PrfA.