Search

G-quadruplexes (G4s) are non-canonical DNA structures that could be considered as potential therapeutic targets for antimicrobial compounds, also known as G4-stabilizing ligands. While some of these ligands are shown in vitro to have a stabilizing effect, the precise mechanism of antibacterial action has not been fully investigated. Here, we employed genome-wide RNA-sequencing to analyze the response of Mycobacterium smegmatis to inhibitory concentrations of BRACO-19 and TMPyP4 G4 ligands. The expression profile changed (FDR |1|) for 822 (515↑; 307↓) genes in M. smegmatis in response to BRACO-19 and for 680 (339↑; 341↓) genes in response to TMPyP4. However, the analysis revealed no significant ligand-induced changes in the expression levels of G4-harboring genes, genes under G4-harboring promoters, or intergenic regions located on mRNA-like or template strands. Meanwhile, for the BRACO-19 ligand, we found significant changes in the replication and repair system genes, as well as in iron metabolism genes which is, undoubtedly, evidence of the induced stress. For the TMPyP4 compound, substantial changes were found in transcription factors and the arginine biosynthesis system, which may indicate multiple biological targets for this compound.

The structure and dynamics of bacterial nucleoids play important roles in regulating gene expression. Bacteria of class Mollicutes and, in particular, mycoplasmas feature extremely reduced genomes. They lack multiple structural proteins of the nucleoid, as well as regulators of gene expression. We studied the organization of Mycoplasma gallisepticum nucleoids in the stationary and exponential growth phases at the structural and protein levels. The growth phase transition results in the structural reorganization of M. gallisepticum nucleoid. In particular, it undergoes condensation and changes in the protein content. The observed changes corroborate with the previously identified global rearrangement of the transcriptional landscape in this bacterium during the growth phase transition. In addition, we identified that the glycolytic enzyme enolase functions as a nucleoid structural protein in this bacterium. It is capable of non-specific DNA binding and can form fibril-like complexes with DNA.

G-quadruplexes (G4s) are non-canonical DNA structures that could be considered as potential therapeutic targets for antimicrobial compounds, also known as G4-stabilizing ligands. While some of these ligands are shown in vitro to have a stabilizing effect, the precise mechanism of antibacterial action has not been fully investigated. Here, we employed genome-wide RNA-sequencing to analyze the response of Mycobacterium smegmatis to inhibitory concentrations of BRACO-19 and TMPyP4 G4 ligands. The expression profile changed (FDR < 0.05, log2FC > |1|) for 822 (515↑; 307↓) genes in M. smegmatis in response to BRACO-19 and for 680 (339↑; 341↓) genes in response to TMPyP4. However, the analysis revealed no significant ligand-induced changes in the expression levels of G4-harboring genes, genes under G4-harboring promoters, or intergenic regions located on mRNA-like or template strands. Meanwhile, for the BRACO-19 ligand, we found significant changes in the replication and repair system genes, as well as in iron metabolism genes which is, undoubtedly, evidence of the induced stress. For the TMPyP4 compound, substantial changes were found in transcription factors and the arginine biosynthesis system, which may indicate multiple biological targets for this compound. [ABSTRACT FROM AUTHOR]

G-quadruplexes (G4s) are non-canonical DNA structures that could be considered as potential therapeutic targets for antimicrobial compounds, also known as G4-stabilizing ligands. While some of these ligands are shown in vitro to have a stabilizing effect, the precise mechanism of antibacterial action has not been fully investigated. Here, we employed genome-wide RNA-sequencing to analyze the response of Mycobacterium smegmatis to inhibitory concentrations of BRACO-19 and TMPyP4 G4 ligands. The expression profile changed (FDR < 0.05, log 2 FC > |1|) for 822 (515↑; 307↓) genes in M. smegmatis in response to BRACO-19 and for 680 (339↑; 341↓) genes in response to TMPyP4. However, the analysis revealed no significant ligand-induced changes in the expression levels of G4-harboring genes, genes under G4-harboring promoters, or intergenic regions located on mRNA-like or template strands. Meanwhile, for the BRACO-19 ligand, we found significant changes in the replication and repair system genes, as well as in iron metabolism genes which is, undoubtedly, evidence of the induced stress. For the TMPyP4 compound, substantial changes were found in transcription factors and the arginine biosynthesis system, which may indicate multiple biological targets for this compound., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shitikov, Bespiatykh, Malakhova, Bespyatykh, Bodoev, Vedekhina, Zaychikova, Veselovsky, Klimina, Ilina and Varizhuk.)