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G-Quadruplex Structures in Microbial DNA - A Role in Basic Biology and a Possible Antimicrobial Target: A Review of Recent Literature and a Proposal
EP29328
G-Quadruplex Structures in Microbial DNA - A Role in Basic Biology and a Possible Antimicrobial Target: A Review of Recent Literature and a Proposal
Submitted on 24 Oct 2018

Singh, Vikal and Leifer, Zev
New York College of Podiatric Medicine
This poster was presented at Labroots Online Conference on Microbiology and Immunology 2018
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Poster Abstract
DNA can assume many unusual local conformational variations, over and above the canonical Watson-Crick double helix. One such structure is the G-quadruplex(G4) formed from a single strand of DNA that contains tracts of guanines (G) that form quartets and stacks of quartets. They have been well-studied in mammalian systems and are notably located in telomeres and promotor sites. Furthermore, recent findings predict the role of G4 motifs in chromatin packaging, recombination, CpG methylation , and genomic translocation in cancer tissues. Thus, they have attracted considerable interest. This poster focuses attention on the microbial world. In bacteria G4 sequences have been reported in Escherichia coli, Deinococcus radiodurans, Xanthomonas and Nostoc species. Evidence of bacterial enzymes that process G4s, such as helicases, has been provided in E.coli, Clostridium difficile and Bacteroides species. Also, bacterial G4s have been implicated in antigenic variation of the cell-surface pilin protein of Neisseria gonorrhoeae. Recent work has convincingly shown G4 structures in virulence processes in several critical microbial pathogens of humans. Interestingly, these come from a range of kingdoms of bacteria and protozoa as well as viruses and all facilitate immune evasion in distinctive ways. Specifically, roles for G4s have been theorized in the antigenic variation systems of bacteria and protozoa, as well as in the silencing of at least two significant viruses, human immunodeficiency virus (HIV) and Epstein-Barr virus(EBV). Yeast, studies have characterized the association of conserved and non-conserved G4 DNA motifs in Saccharomyces cerevisiae with more than 40 known genome features and gene classes .With regard to viruses, there is evidence indicating a possible role of G4 structures in a virus life cycle as well as the use of G4-forming oligonucleotides as potential antiviral agents and innovativetools. With many of these organisms, work is underway to develop small molecules that can interact with the G-quadruplex structure to inhibit the growth of the organism. This poster presents a summary of these findings in the literature and a sample of relevant citations. A proposal is discussed that suggests
that these studies form part of a larger world of DNA structural changes that can be induced by small molecule ligands, especially insofar as these changes affect the binding of regulatory proteins or affect other biological functions. This, in turn, may lead to the discovery of new antimicrobial agents that act by affecting G4 structures of other unusual DNA forms.

G-quadruplexes in pathogens: A common route to virulence control? Harris, L.M. and Merrick, C.J. PLoSPathog. 11(2) 2015
Mapping and characterization of G-quadruplexes in M. tuberculosis gene promotor regions. Perrone, et al. Nature Scientific Reports 7:5743, 2017.
G-quadruplexes in viruses: function and potential therapeutic application. Metifiot, et al. Nucleic Acids Research. 42: 12352, 2014
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