Neisseria meningitidis Uses Sibling Small Regulatory RNAs To Switch from Cataplerotic to Anaplerotic Metabolism

Abstract

Neisseria meningitidis (the meningococcus) is primarily a commensal of the human oropharynx that sporadically causes septicemia and meningitis. Meningococci adapt to diverse local host conditions differing in nutrient supply, like the nasopharynx, blood, and cerebrospinal fluid, by changing metabolism and protein repertoire. However, regulatory transcription factors and two-component systems in meningococci involved in adaptation to local nutrient variations are limited. We identified novel sibling small regulatory RNAs (Neisseria metabolic switch regulators [NmsRs]) regulating switches between cataplerotic and anaplerotic metabolism in this pathogen. Overexpression of NmsRs was tolerated in blood but not in cerebrospinal fluid. Expression of six tricarboxylic acid cycle enzymes was downregulated by direct action of NmsRs. Expression of the NmsRs themselves was under the control of the stringent response through the action of RelA. Small sibling regulatory RNAs of meningococci, controlling general metabolic switches, add an exciting twist to their versatile repertoire in bacterial pathogens.

Regulation of Neisseria meningitidis cytochrome bc1 components by NrrF, a Fur‐controlled small noncoding RNA

“…Instead, sdhCDAB was shown to be regulated by NrrF [21,22], demonstrating crosstalk between the riboregulated network and the Fur-regulated network in meningococci. By using a well-established heterologous (Escherichia coli) reporter system for translational control and target recognition of sRNA in vivo, we showed a direct interaction between NmsR-A and sdhC [20,28]; though, we did not observe regulation in meningococci. The regulation of sdhC by multiple sRNA has been shown before, and sdhCDAB might thus be the first example of a cistronic mRNA in meningococci that is subjected to regulation by two different sRNA species [29].…”

Identification of small RNAs abundant in Burkholderia cenocepacia biofilms reveal putative regulators with a potential role in carbon and iron metabolism

“…The double-hairpin RNAs bear structural similarities to NmsRs, two homologous sRNAs occurring as tandems in the genome of Neisseria meningitidis , a pathogenic beta-proteobacterium 43 . Both NmsRs contain two CU-rich stretches which are located in unpaired regions of their secondary structure, and which show complementarity to the RBS regions of genes of the tricarbolic acid (TCA) cycle; these genes were also up-regulated in a NmsR double-deletion mutant 43 . Double-hairpin RNAs occur not in tandem, their up to five homologues are distributed throughout Burkholderia genomes.…”

Loving the poison: the methylcitrate cycle and bacterial pathogenesis

“…The expression of several TCA cycle-associated genes (including prpF, prpB, acnB and prpC) were down-regulated by the direct action of NmsRs. Expression of the NmsRs themselves was under the control of the stringent response through the action of the (p)ppGpp synthase, RelA [25], suggesting that the use of propionate may become crucial in this organism under conditions of nutrient limitation [26].…”