Abstract
The Mycobacterium tuberculosis protein encoded by the Rv1986 gene is a target for memory T cells in patients with tuberculosis, and shows strong similarities to a lysine exporter LysE of Corynebacterium glutamicum. During infection, the pathogen Mycobacterium tuberculosis adapts its metabolism to environmental changes. In this study, we found that the expression of Rv1986 is controlled by Rv1985c. Rv1985c is located directly upstream of Rv1986 with an overlapping promoter region between both genes. Semiquantitative reverse transcription PCR using an isogenic mutant of Mycobacterium tuberculosis lacking Rv1985c showed that in the presence of lysine, Rv1985c protein positively upregulated the expression of Rv1986. RNA sequencing revealed the transcription start points for both transcripts and overlapping promoters. An inverted repeat in the center of the intergenic region was identified, and binding of Rv1985c protein to the intergenic region was confirmed by electrophoretic mobility shift assays. Whole transcriptome expression analysis and RNAsequencing showed downregulated transcription of ppsBCD in the Rv1985c-mutant compared to the wild type strain. Taken together, our findings characterize the regulatory network of Rv1985c in Mycobacterium tuberculosis. Due to their similarity of an orthologous gene pair in Corynebacterium glutamicum, we suggest to rename Rv1985c to lysG(Mt), and Rv1986 to lysE(Mt).
Highlights
Mycobacterium tuberculosis (Mt) is the agent of tuberculosis and the most frequent bacterial killer worldwide due to a single infectious agent [1]
Due to the fact that the gene products of both, Rv1985c and Rv1986 [renamed in this study as LysG(Mt) and LysE(Mt)], are homologues to LysG and LysE in C. glutamicum, we were interested in studying the LysG(Mt) / LysE(Mt) regulatory unit
The HTH motif itself has the same length of 22 amino acids in ArgP and LysG(Mt), while the length of the HTH motif in LysG of C. glutamicum is 25 amino acids
Summary
Mycobacterium tuberculosis (Mt) is the agent of tuberculosis and the most frequent bacterial killer worldwide due to a single infectious agent [1]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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