The well conserved protein Hfq has emerged as the key modulator of riboregulation in bacteria. It is thought to function as an RNA chaperone and facilitate base-pairing between small regulatory RNA (sRNA) and the mRNA targets, and many sRNAs are dependent on the Hfq protein for their regulatory functions. To address the possible role of Hfq in riboregulated circuits in Neisseria meningitidis we generated a Hfq mutant of the MC58 strain and the knockout mutant shows pleiotropic phenotypes: it has a general growth phenotype in vitro in culture media, it is sensitive to a wide range of stresses including those that it may encounter in the host. Furthermore, the expression profile of a vast number of proteins is clearly altered in the mutant and we have identified 27 proteins by proteomics. All of the phenotypes tested to date are also restored by complementation of Hfq expression in the mutant strain. Importantly, in ex vivo and in vivo models of infection the Hfq mutant is attenuated. These data indicate that Hfq plays a key role in stress response and virulence and proposes a major role for Hfq in regulation of gene expression. Moreover, this study suggests that in meningococcus there is a large Hfq-mediated sRNA network which is as yet largely unexplored.

The RNA chaperone Hfq is involved in the stress response and virulence in Neisseria meningitidis and is a pleiotropic regulator of protein expression

FANTAPPIE', LAURA;METRUCCIO, MATTEO MARIA EMILIANO;SCARLATO, VINCENZO;
2009

Abstract

The well conserved protein Hfq has emerged as the key modulator of riboregulation in bacteria. It is thought to function as an RNA chaperone and facilitate base-pairing between small regulatory RNA (sRNA) and the mRNA targets, and many sRNAs are dependent on the Hfq protein for their regulatory functions. To address the possible role of Hfq in riboregulated circuits in Neisseria meningitidis we generated a Hfq mutant of the MC58 strain and the knockout mutant shows pleiotropic phenotypes: it has a general growth phenotype in vitro in culture media, it is sensitive to a wide range of stresses including those that it may encounter in the host. Furthermore, the expression profile of a vast number of proteins is clearly altered in the mutant and we have identified 27 proteins by proteomics. All of the phenotypes tested to date are also restored by complementation of Hfq expression in the mutant strain. Importantly, in ex vivo and in vivo models of infection the Hfq mutant is attenuated. These data indicate that Hfq plays a key role in stress response and virulence and proposes a major role for Hfq in regulation of gene expression. Moreover, this study suggests that in meningococcus there is a large Hfq-mediated sRNA network which is as yet largely unexplored.
Fantappiè L; Metruccio MM; Seib KL; Oriente F; Cartocci E; Ferlicca F; Giuliani MM; Scarlato V; Delany I
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/72149
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