G-Quadruplex Structures in Bacteria - Biological Relevance and Potential as Antimicrobial Target

ABSTRACT

DNA strand consisting of multiple runs of guanines can adopt the non-canonical, four-stranded DNA secondary structure known as G-quadruplex or G4 DNA. G4 DNA is thought to play an important role in transcriptional and translational regulation of genes, DNA replication, genome stability, and oncogene expression in eukaryotic genomes. In other organisms including several bacterial pathogens and some plant species, the biological role of G4 DNA and G4 RNA is starting to be explored. Recent investigation showed that G4 DNA and G4 RNA are generally conserved across plant species. In silico analyses of several bacterial genomes identified the putative guanine-rich, G4 DNA-forming sequences in the promoter regions. They were particularly abundant in certain gene classes, suggesting that these highly diverse structures can be employed to regulate expression of genes involved in secondary metabolite synthesis and signal transduction. Furthermore, in the pathogen Mycobacterium tuberculosis, the distribution of G4 motifs and their potential role in the regulation of gene transcription advocate for the use of G4 ligands to develop novel antitubercular therapies. In this review, we discuss the various roles of G4 structures in bacterial DNA and the application of G4 DNA as an inhibitor or therapeutic agent to tackle the bacterial pathogens.