4.5 Article

Conserved G-Quadruplex Motifs Regulate Gene Expression in Neisseria meningitidis

Journal

ACS INFECTIOUS DISEASES
Volume 8, Issue 4, Pages 728-743

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsinfecdis.1c00383

Keywords

noncanonical structures; drug targets; G-quadruplex; Neisseria meningitidis; virulence; growth

Funding

  1. MHRD, New Delhi
  2. CSIR, New Delhi

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Conserved G-quadruplex motifs have been found in Neisseria meningitidis, which are linked to essential genes involved in cell adhesion, pathogenesis, virulence, and DNA repair.
The noncanonical structures, G-quadruplexes (GQs), formed in the guanine-rich region of nucleic acids regulatevarious biological and molecular functions in prokaryotes and eukaryotes.Neisseria meningitidisis a commensal residing in a human'supper respiratory tract but occasionally becomes virulent, causing life-threatening septicemia and meningitis. The factors causing these changes in phenotypes are not fully understood. At the molecular level, regulatory components help in a clearer understanding of the pathogen's virulence and pathogenesis. Herein, genome analysis followed by biophysical assays and cell-based experimentsrevealed the presence of conserved GQ motifs inN. meningitidis. These GQs are linked to the essential genes involved in celladhesion, pathogenesis, virulence, transport, DNA repair, and recombination. Primer extension stop assay, reporter assays, and quantitative real-time polymerase chain reaction (qRT-PCR) further affirmed the formation of stable GQsin vitroandin vivo. These results support the existence of evolutionarily conserved GQ motifs inN. meningitidisand uphold the usage of GQ-specific ligands as novel antimeningococcal therapeutics

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