Rifampicin is a clinically important antibiotic that binds to, and blocks the DNA/RNA channel of bacterial RNA polymerase (RNAP). Stalled, nonfunctional RNAPs can be removed from DNA by HelD proteins; this is important for maintenance of genome integrity. Recently, it was reported that HelD proteins from high G+C Actinobacteria, called HelR, are able to dissociate rifampicin-stalled RNAPs from DNA and provide rifampicin resistance. This is achieved by the ability of HelR proteins to dissociate rifampicin from RNAP. The HelR-mediated mechanism of rifampicin resistance is discussed here, and the roles of HelD/HelR in the transcriptional cycle are outlined. Moreover, the possibility that the structurally similar HelD proteins from low G+C Firmicutes may be also involved in rifampicin resistance is explored. Finally, the discovery of the involvement of HelR in rifampicin resistance provides a blueprint for analogous studies to reveal novel mechanisms of bacterial antibiotic resistance.

Cryogenic Electron Microscopy Research Service Group Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Flemingovo náměstí 2 16000 Prague Czech Republic

Laboratory of Microbial Genetics and Gene Expression Institute of Microbiology of the Czech Academy of Sciences Vídeňská 1083 14220 Prague Czech Republic

Laboratory of Structure and Function of Biomolecules Institute of Biotechnology of the Czech Academy of Sciences Centre BIOCEV Průmyslová 595 25250 Vestec Czech Republic

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Mycobacterial HelD connects RNA polymerase recycling with transcription initiation