Molecular characterization and identification of proteins regulated by Hfq in Neisseria meningitidis.
Hfq is a highly conserved pleiotropically acting prokaryotic RNA-binding protein involved in the post-transcriptional regulation of many stress-responsive genes by small RNAs. In this study, we show that Hfq of the strictly human pathogen Neisseria meningitidis is involved in the regulation of expression of components involved in general metabolic pathways, iron metabolism and virulence. A meningococcal hfq deletion strain (H44/76Deltahfq) is impaired in growth in nutrient-rich media and does not grow at all in nutrient-limiting medium. The growth defect was complemented by expression of hfq in trans. Using proteomics, the expression of 28 proteins was found to be significantly affected upon deletion of hfq. Of these, 20 proteins are involved in general metabolism, among them seven iron-responsive genes. Two proteins (PilE, TspA) are involved in adherence to human cells, a step crucial for the onset of disease. One of the differentially expressed proteins, GdhA, was identified as an essential virulence factor for establishment of sepsis in an animal model, studied earlier. These results show that in N. meningitidis Hfq is involved in the regulation of a variety of components contributing to the survival and establishment of meningococcal disease.
Yvonne
Y
Pannekoek
Robert
R
Huis in 't Veld
Carla Th P
CT
Hopman
Ankie A J
AA
Langerak
Dave
D
Speijer
Arie
A
van der Ende
D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000096:biosynthesis; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D017124:Conserved Sequence; D015964:Gene Expression Regulation, Bacterial; D035001:Host Factor 1 Protein / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008589:Meningococcal Infections / Q000382:microbiology*; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D020539:Sequence Analysis, Protein; D037521:Virulence Factors / Q000096:biosynthesis
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015815:Cell Adhesion Molecules; D035001:Host Factor 1 Protein; C120045:TspA protein, Neisseria meningitidis; D037521:Virulence Factors