A central role of sibling sRNAs NgncR_162/163 in main metabolic pathways of Neisseria gonorrhoeae

Bacterial regulatory RNAs (sRNAs) have been implicated in the regulation of numerous metabolic pathways. In most of these studies, sRNA-dependent regulation of mRNAs or proteins of enzymes in metabolic pathways has been predicted to affect the metabolism of these bacteria. However, only in very few cases has the role in metabolism been demonstrated. We performed here a combined transcriptome and metabolome analysis to define the regulon of the sibling sRNAs NgncR\_162 and NgncR\_163 and their impact on the metabolism of the major human pathogen Neisseria gonorrhoeae . These sRNA have previously been shown to control genes of the citric acid and methylcitrate cycle by post-transcriptional negative regulation. By transcriptome analysis we expand the NgncR\_162/163 regulon by several new members and provide evidence that the sibling sRNAs act as both negative and positive regulators of target gene expression. Newly identified NgncR\_162/163 targets are mostly involved in transport processes, especially the uptake of glycine, branched chain amino acids and phenylalanine. NgncR\_162/163 also play key roles in the control of serine-glycine metabolism and hence probably affect biosynthesis of nucleotides, vitamins and other amino acids via the supply of C1-units. Metabolic flux analysis demonstrated a bipartite metabolism with glucose degradation providing intermediates for anabolic pathways, while energy metabolism via the citric acid cycle is mainly driven by amino acids, which feed into the cycle. Thus, by combined RNA-seq and metabolomics we significantly extended the regulon of NgncR\_162/163 and demonstrate their role in the regulation of central metabolic pathways of the gonococcus. ### Competing Interest Statement The authors have declared no competing interest.