The RNA chaperone Hfq is involved in stress response and virulence in Neisseria meningitidis and is a pleiotropic regulator of protein expression.
The well-conserved protein Hfq has emerged as the key modulator of riboregulation in bacteria. This protein is thought to function as an RNA chaperone and to facilitate base pairing between small regulatory RNA (sRNA) and 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 an Hfq mutant of the MC58 strain, and the knockout mutant has pleiotropic phenotypes; it has a general growth phenotype in vitro in culture media, and 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 we propose 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 so far is largely unexplored.
Fantappiè
Laura
L
Novartis Vaccines, Via Fiorentina 1, 53100 Siena, Italy. isabel.delany@novartis.com
Metruccio
Matteo M E
MM
Seib
Kate L
KL
Oriente
Francesca
F
Cartocci
Elena
E
Ferlicca
Francesca
F
Giuliani
Marzia M
MM
Scarlato
Vincenzo
V
Delany
Isabel
I
D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D001769:Blood / Q000382:microbiology; D015169:Colony Count, Microbial; D015180:Electrophoresis, Gel, Two-Dimensional; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D055786:Gene Knockout Techniques; D005816:Genetic Complementation Test; D035001:Host Factor 1 Protein / Q000235:genetics / Q000502:physiology*; D006801:Humans; D013058:Mass Spectrometry; D008589:Meningococcal Infections / Q000382:microbiology; D050296:Microbial Viability; D009345:Neisseria meningitidis / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D051381:Rats; D013312:Stress, Physiological; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis* / Q000302:isolation & purification
D001426:Bacterial Proteins; D035001:Host Factor 1 Protein; D037521:Virulence Factors