G-Quadruplexes: More Than Just a Kink in Microbial Genomes

G-quadruplexes (G4s) are noncanonical nucleic acid secondary structures formed by guanine-rich DNA and RNA sequences. In this review we aim to provide an overview of the biological roles of G4s in microbial genomes with emphasis on recent discoveries. G4s are enriched and conserved in the regulatory regions of microbes, including bacteria, fungi, and viruses. Importantly, G4s in hepatitis B virus (HBV) and hepatitis C virus (HCV) genomes modulate genes crucial for virus replication. Recent studies on Epstein–Barr virus (EBV) shed light on the role of G4s within the microbial transcripts as cis-acting regulatory signals that modulate translation and facilitate immune evasion. Furthermore, G4s in microbial genomes have been linked to radioresistance, antigenic variation, recombination, and latency. G4s in microbial genomes represent novel therapeutic targets for antimicrobial therapy. G4s display functional diversity among microbes. Their ability to influence molecular processes, including replication, transcription, translation, and recombination, has implications for the observed microbial phenotypes, including latency, virulence, rapid evolution, and radioresistance. Quadruplexes are increasingly being recognized as novel therapeutic targets in microbes. Several reports convincingly demonstrate antimicrobial activity of quadruplex-binding ligands against clinically challenging pathogens, including HIV-1, HCV, Ebola virus, Plasmodium falciparum, and Mycobacterium tuberculosis.