Elements in the LftR Repressor Operator Interface Contributing to Regulation of Aurantimycin Resistance in Listeria monocytogenes.

The bacterium ubiquitously occurs in the environment but can cause severe invasive disease in susceptible individuals when ingested. We recently identified the genes and , encoding a multidrug resistance ABC transporter and a regulatory module, respectively. These genes jointly mediate resistance against aurantimycin, an antibiotic produced by the soil-dwelling species , and thus contribute to the survival of in its natural habitat, the soil. Repression of and is exceptionally tight but strongly induced in the presence of aurantimycin. Repression depends on LftR, which belongs to subfamily 2 of the PadR-like transcriptional repressors. To better understand this interesting class of transcriptional repressors, we here deduce the LftR operator sequence from a systematic truncation and mutation analysis of the P promoter. The sequence identified is also present in the P promoter but not found elsewhere in the chromosome. Mutational analysis of the putative operator in the P promoter confirmed its relevance for LftR-dependent repression. The proposed operator sequence was sufficient for DNA binding by LftR , and a mutation in this sequence affected aurantimycin resistance. Our results provide further insights into the transcriptional adaptation of an important human pathogen to survive the conditions in its natural reservoir. is an environmental bacterium that lives in the soil but can infect humans upon ingestion, and this can lead to severe invasive disease. Adaptation to these entirely different habitats involves massive reprogramming of transcription. Among the differentially expressed genes is the operon, which encodes a transporter for the detoxification of aurantimycin, an antimicrobial compound produced by soil-dwelling competitors. While is important for survival in the environment, its expression is detrimental during infection. We here identify critical elements in the promoter and its transcriptional regulator LftR that contribute to habitat-specific expression of the genes. These results further clarify the molecular mechanisms underlying the aurantimycin resistance of .