Periodontitis is the most common inflammatory disease responsible for tooth loss in adults, in which severe periodontitis is the sixth-most prevalent condition in the world, affecting approximately 50% of people over 30 years old in United States, 30.6% of people over 35 years old in mainland China, and 1.1 billion people worldwide [1]. Periodontitis is triggered by dental plaque and the “keystone” periodontopathogen of plaque is Porphyromonas gingivalis, a gram-negative anaerobic and black-pigmented bacterium [2]. Multiple systemic diseases including respiratory, cardiovascular and neurodegenerative diseases have also been demonstrated to be closely correlated with P. gingivalis, indicating the infection of P. gingivalis impacts the overall human health [3]. Broad-spectrum metronidazole and amoxicillin, targeting DNA and cell wall synthesis respectively, are the common first-line drugs for controlling the plaque during treating periodontitis in addition to scaling and root planning, yet increasingly occurred antibiotic resistance has weakened the effectiveness of their clinical performance [4]. Another principal targeting site of P. gingivalis for specific drug development is RNA polymerase (RNAP), the essential enzyme responsible for gene transcription. However, P. gingivalis RNAP exhibited different antibiotic sensitivity profile from Escherichia coli RNAP [5], suggesting structural inconsistency may present between them and also necessitating the structural determination of P. gingivalis RNAP for precise drug development.

Here, we report the cryo-EM structure of P. gingivalis RNAP at 3.5 Å resolution, illustrating the overall architecture of P. gingivalis RNAP and revealing key structure differences between P. gingivalis and E. coli RNAPs, and suggest a potential previously unknown role of ω subunit in transcription initiation of anaerobic bacteria.