AN RNA-BASED ANTIBIOTIC SENSOR CONTROLS ANTIBIOTIC RESISTANCE IN LISTERIA MONOCYTOGENES

Regulated activation of antibiotic resistance allows bacteria to maintain resistance genes despite their high fitness costs. Here we report the antibiotic-dependent regulation of a novel resistance gene in the human pathogen Listeria monocytogenes. We find that resistance to lincomycin, a translation inhibiting antibiotic, is controlled by a cis-acting ribo-regulator that specifically senses this antibiotic. While the promoter of the gene is constitutively active, transcription is aborted prematurely and gene expression is suppressed in the absence of lincomycin. However, in the presence of the antibiotic a specific structure in the 5’ UTR is modified to allow productive transcription, leading to elevated lincomycin resistance. Using further computational, genetic and biochemical approaches we revealed that this regulator functions via a unique ribosome-dependent mechanism that is able to specifically detect lincomycin but not other antibiotics. Remarkably, we find that this regulation is highly conserved in bacteria, suggesting an important role for this ribo-regulator in conferring antibiotic resistance throughout evolution.