FG11 Division of Enteropathogenic Bacteria and Legionella, Robert Koch Institute, Wernigerode, Germany.
FG11 Division of Enteropathogenic Bacteria and Legionella, Robert Koch Institute, Wernigerode, Germany
J Bacteriol. 2021 Apr 21;203(10). doi: 10.1128/JB.00503-20.
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 .
这种细菌在环境中普遍存在，但当被摄入时，它会在易感个体中引起严重的侵袭性疾病。我们最近确定了 和 基因，分别编码一种多药耐药 ABC 转运蛋白和一个调节模块。这两个基因共同介导了对土生土长的 产生的抗生素 aurantimycin 的抗性，从而有助于 在其自然栖息地土壤中的生存。 和 的抑制作用非常紧密，但在 aurantimycin 存在的情况下强烈诱导。抑制作用依赖于 LftR，它属于 PadR 样转录抑制剂亚家族 2。为了更好地理解这一类有趣的转录抑制剂，我们在这里从 P 启动子的系统截断和突变分析中推导出 LftR 操纵子序列。所确定的序列也存在于 P 启动子中，但在染色体的其他地方没有发现。对 P 启动子中推定操纵子的突变分析证实了其与 LftR 依赖性抑制作用的相关性。该提议的操纵子序列足以与 LftR 结合 DNA，该序列中的突变会影响 aurantimycin 的抗性。我们的结果进一步深入了解了一种重要的人类病原体如何适应其自然储层中的条件以生存。 是一种生活在土壤中的环境细菌，但在摄入后会感染人类，这可能导致严重的侵袭性疾病。适应这些完全不同的栖息地涉及转录的大规模重编程。差异表达的基因中包括 操纵子，该操纵子编码一种用于解毒 aurantimycin 的转运蛋白，aurantimycin 是一种由土壤竞争物产生的抗菌化合物。虽然 在环境中生存很重要，但在感染期间其表达是有害的。我们在这里确定了 启动子及其转录调节剂 LftR 中的关键元件，这些元件有助于 基因在特定栖息地的表达。这些结果进一步阐明了 对 aurantimycin 抗性的分子机制。
