title: Transcriptional profiling of serogroup B Neisseria meningitidis growing in human blood: an approach to vaccine antigen discovery.
abstract: Neisseria meningitidis is a nasopharyngeal commensal of humans which occasionally invades the blood to cause septicaemia. The transcriptome of N. meningitidis strain MC58 grown in human blood for up to 4 hours was determined and around 10% of the genome was found to be differentially regulated. The nuo, pet and atp operons, involved in energy metabolism, were up-regulated, while many house-keeping genes were down-regulated. Genes encoding protein chaperones and proteases, involved in the stress response; complement resistant genes encoding enzymes for LOS sialylation and biosynthesis; and fHbp (NMB1870) and nspA (NMB0663), encoding vaccine candidates, were all up-regulated. Genes for glutamate uptake and metabolism, and biosynthesis of purine and pyrimidine were also up-regulated. Blood grown meningococci are under stress and undergo a metabolic adaptation and energy conservation strategy. The localisation of four putative outer membrane proteins encoded by genes found to be up-regulated in blood was assessed by FACS using polyclonal mouse antisera, and one (NMB0390) showed evidence of surface expression, supporting its vaccine candidacy.
authors: Section of Paediatrics, Department of Medicine, Imperial College London, St. Mary's Campus, London, United Kingdom.
authors: Åsa K
authors: ÅK
authors: Hedman
authors: Asa K
authors: AK
authors: Hedman
authors: Ming-Shi
authors: MS
authors: Li
authors: Paul R
authors: PR
authors: Langford
authors: J Simon
authors: JS
authors: Kroll
mesh_terms: D000328:Adult; D005434:Flow Cytometry; D006801:Humans; D008589:Meningococcal Infections / Q000097:blood / Q000382:microbiology; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome / Q000235:genetics*