ArticleNucleic acids research2021
Structures of Neisseria gonorrhoeae MtrR-operator complexes reveal molecular mechanisms of DNA recognition and antibiotic resistance-conferring clinical mutations.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 20 citations in OpenAlex.
- Designing modular genetic sensors with TtgR/AcrR family transcriptional regulators by using a statistical and data-driven approach.Nucleic acids research · 2025Article
- RND/HAE-1 members in the Pseudomonadota phylum: exploring multidrug resistance.Biophysical reviews · 2025Review
- Genetic identification of mutations and MLST types associated with decreased susceptibility to ceftriaxone inFrontiers in microbiology · 2025Article
- Molecular basis for the transcriptional regulation of an epoxide-based virulence circuit in Pseudomonas aeruginosa.Nucleic acids research · 2024Article
- Structural and functional diversity of Resistance-Nodulation-Division (RND) efflux pump transporters with implications for antimicrobial resistance.Microbiology and molecular biology reviews : MMBR · 2024Review
- Hormonal steroids induce multidrug resistance and stress response genes in Neisseria gonorrhoeae by binding to MtrR.Nature communications · 2024Article
- Molecular basis for the transcriptional regulation of an epoxide-based virulence circuit inbioRxiv : the preprint server for biology · 2024Article
- Structures of the DarR transcription regulator reveal unique modes of second messenger and DNA binding.Nature communications · 2023Article
- Mutation Analysis in Regulator DNA-Binding Regions for Antimicrobial Efflux Pumps in 17,000Microorganisms · 2023Article
- Travel-associated lineages and unique endemic antimicrobial-susceptible lineages ofMicrobial genomics · 2023Article
- Azithromycin Susceptibility Testing and Molecular Investigation ofAntibiotics (Basel, Switzerland) · 2023Article
- PotentmSphere · 2022Article
- Transcriptional regulation of theMicrobiology (Reading, England) · 2022Review
- A Unique Sequence Is Essential for Efficient Multidrug Efflux Function of the MtrD Protein ofmBio · 2021Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations within the mtrR gene are commonly found amongst multidrug resistant clinical isolates of Neisseria gonorrhoeae, which has been labelled a superbug by the Centers for Disease Control and Prevention. These mutations appear to contribute to antibiotic resistance by interfering with the ability of MtrR to bind to and repress expression of its target genes, which include the mtrCDE multidrug efflux transporter genes and the rpoH oxidative stress response sigma factor gene. However, the DNA-recognition mechanism of MtrR and the consensus sequence within these operators to which MtrR binds has remained unknown. In this work, we report the crystal structures of MtrR bound to the mtrCDE and rpoH operators, which reveal a conserved, but degenerate, DNA consensus binding site 5'-MCRTRCRN4YGYAYGK-3'. We complement our structural data with a comprehensive mutational analysis of key MtrR-DNA contacts to reveal their importance for MtrR-DNA binding both in vitro and in vivo. Furthermore, we model and generate common clinical mutations of MtrR to provide plausible biochemical explanations for the contribution of these mutations to multidrug resistance in N. gonorrhoeae. Collectively, our findings unveil key biological mechanisms underlying the global stress responses of N. gonorrhoeae.
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