Neisseria meningitidisUses Sibling Small Regulatory RNAs To Switch from Cataplerotic to Anaplerotic Metabolism.
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 (Neisseriametabolicswitchregulators [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.IMPORTANCERegulatory small RNAs (sRNAs) of pathogens are coming to be recognized as highly important components of riboregulatory networks, involved in the control of essential cellular processes. They play a prominent role in adaptation to physiological changes as represented by different host environments. They can function as posttranscriptional regulators of gene expression to orchestrate metabolic adaptation to nutrient stresses. Here, we identified highly conserved sibling sRNAs inNeisseria meningitidiswhich are functionally involved in the regulation of gene expression of components of the tricarboxylic acid cycle. These novel sibling sRNAs that function by antisense mechanisms extend the so-called stringent response which connects metabolic status to colonization and possibly virulence as well as pathogenesis in meningococci.
Department of Medical Microbiology, Center for Infection and Immunity (CINIMA), Academic Medical Center, Amsterdam, The Netherlands y.pannekoek@amc.uva.nl.
Yvonne
Y
Pannekoek
Department of Medical Microbiology, Center for Infection and Immunity (CINIMA), Academic Medical Center, Amsterdam, The Netherlands.
Robert A G
RA
Huis In 't Veld
Department of Medical Microbiology, Center for Infection and Immunity (CINIMA), Academic Medical Center, Amsterdam, The Netherlands.
Kim
K
Schipper
Department of Medical Microbiology, Center for Infection and Immunity (CINIMA), Academic Medical Center, Amsterdam, The Netherlands.
Sandra
S
Bovenkerk
Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands.
Gertjan
G
Kramer
Department of Neurology, Amsterdam Neuroscience, Academic Medical Center, Amsterdam, The Netherlands.
Matthijs C
MC
Brouwer
Department of Neurology, Amsterdam Neuroscience, Academic Medical Center, Amsterdam, The Netherlands.
Diederik
D
van de Beek
Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands.
Dave
D
Speijer
Department of Medical Microbiology, Center for Infection and Immunity (CINIMA), Academic Medical Center, Amsterdam, The Netherlands.
Arie
A
van der Ende
D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D009345:Neisseria meningitidis / Q000235:genetics* / Q000378:metabolism*; D012329:RNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D058727:RNA, Small Untranslated / Q000235:genetics* / Q000378:metabolism*
D012329:RNA, Bacterial; D058727:RNA, Small Untranslated
Neisseria meningitidis; metabolic regulation; pathogenesis; sibling sRNAs; small regulatory RNAs; stringent response