Transcriptional profiling of Mycobacterium smegmatis exposed to subinhibitory concentrations of G4-stabilizing ligands

Zaychikova MV, Bespiatykh DA, Malakhova MV, Bodoev IN, Vedekhina TS, Veselovsky VA, Klimina KM, Varizhuk AM, Shitikov EA
About authors

Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia

Correspondence should be addressed: Egor A. Shitikov
Malaya Pirogovskaya, 1a, Moscow, 119435, Russia; ur.liam@vokitihse

About paper

Funding: the study was funded by the Russian Science Foundation, project number 19-75-10109

Author contribution: Zaychikova MV — literature analysis, data analysis and interpretation, manuscript drafting; Bespiatykh DA — literature analysis, data analysis, manuscript drafting; Malakhova MV — research planning and implementation; Bodoev IN — literature analysis, data analysis, manuscript drafting; Vedekhina TS — research implementation, data interpretation; Veselovsky VA — research implementation, data analysis; Klimina KM — research implementation, data analysis and interpretation; Varizhuk AM — research planning and implementation, data interpretation; Shitikov EA — research planning, literature analysis, data analysis, manuscript drafting.

Received: 2022-04-08 Accepted: 2022-04-30 Published online: 2022-05-15
Fig. 1. Structural formulas of the BRACO-19 and TMPyP4 ligands
Fig. 2. Transcriptomic differences revealed in Mycobacterium smegmatis treated with different concentrations of BRACO-19 and TMPyP4. A. The principal components analysis shows correlations of gene expression levels under five sets of conditions (designated by colors). B. Venn diagrams show intersections among the sets of genes regulated by exposure to BRACO-19 and TMPyP4 in different concentrations
Fig. 3. Boxplot showing differential expression of PQS-containing genes in Mycobacterium smegmatis exposed to different concentrations of BRACO-19 and TMPyP4. The number of genes with PQS (n) excludes genes with low CPM (Counts Per Million); for PQS in intergenic regions, both flanking genes are included. Box limits correspond to lower and upper quartiles; horizontal line inside the box indicates the median and black dot indicates the mean value. Games-Howell post hoc test was applied to calculate p values
Fig. 4. Mean-difference plots (MD-plots) of fold changes (log2 FC) versus average expression levels (log2 CPM) for the putative quadruplex-associated genes
Fig. 5. GO categories and KEGG pathways showing enrichment under exposure to BRACO-19 and TMPyP4 in different concentrations: GO:0006810 — Transport; GO:0006526 — Arginine biosynthesis; GO:0006351 — DNA-dependent transcription; msm02010 — ABC transporters; msm01053 — Biosynthesis of siderophore group nonribosomal peptides; msm00920 — Sulfur metabolism
Table. Changes in the replication and repair system gene expression in M. smegmatis under the action of BRACO-19 and TMPyP4
Note: * — bold typed are entries complying with the following criteria: more than 2-fold change and FDR < 0.05.