UNIGE document Scientific Article
previous document  unige:25448  next document
add to browser collection
Title

Transcriptome analysis of Neisseria meningitidis in human whole blood and mutagenesis studies identify virulence factors involved in blood survival

Authors
Echenique-Rivera, Hebert
Muzzi, Alessandro
Del Tordello, Elena
Seib, Kate L
Rappuoli, Rino
Pizza, Mariagrazia
Serruto, Davide
Published in PLOS Pathogens. 2011, vol. 7, no. 5, p. e1002027
Abstract During infection Neisseria meningitidis (Nm) encounters multiple environments within the host, which makes rapid adaptation a crucial factor for meningococcal survival. Despite the importance of invasion into the bloodstream in the meningococcal disease process, little is known about how Nm adapts to permit survival and growth in blood. To address this, we performed a time-course transcriptome analysis using an ex vivo model of human whole blood infection. We observed that Nm alters the expression of ≈30% of ORFs of the genome and major dynamic changes were observed in the expression of transcriptional regulators, transport and binding proteins, energy metabolism, and surface-exposed virulence factors. In particular, we found that the gene encoding the regulator Fur, as well as all genes encoding iron uptake systems, were significantly up-regulated. Analysis of regulated genes encoding for surface-exposed proteins involved in Nm pathogenesis allowed us to better understand mechanisms used to circumvent host defenses. During blood infection, Nm activates genes encoding for the factor H binding proteins, fHbp and NspA, genes encoding for detoxifying enzymes such as SodC, Kat and AniA, as well as several less characterized surface-exposed proteins that might have a role in blood survival. Through mutagenesis studies of a subset of up-regulated genes we were able to identify new proteins important for survival in human blood and also to identify additional roles of previously known virulence factors in aiding survival in blood. Nm mutant strains lacking the genes encoding the hypothetical protein NMB1483 and the surface-exposed proteins NalP, Mip and NspA, the Fur regulator, the transferrin binding protein TbpB, and the L-lactate permease LctP were sensitive to killing by human blood. This increased knowledge of how Nm responds to adaptation in blood could also be helpful to develop diagnostic and therapeutic strategies to control the devastating disease cause by this microorganism.
Keywords Adaptation, PhysiologicalAdultAntigens, Bacterial/geneticsBacteremia/blood/microbiologyBacterial Proteins/geneticsCluster AnalysisDown-Regulation/geneticsFemaleGene Expression Regulation, Bacterial/geneticsGenes, Bacterial/geneticsGenome, Bacterial/geneticsHost-Pathogen Interactions/geneticsHumansMaleMeningococcal Infections/blood/microbiologyModels, BiologicalNeisseria meningitidis, Serogroup B/genetics/growth & development/pathogenicity/physiologyRNA, Bacterial/geneticsSequence DeletionTranscriptomeUp-Regulation/geneticsVirulence Factors/genetics
Identifiers
PMID: 21589640
Full text
Article (Published version) (2.4 MB) - public document Free access
Structures
Research group Analyse génomique et fonctionnelle du staphylocoque doré (604)
Citation
(ISO format)
ECHENIQUE-RIVERA, Hebert et al. Transcriptome analysis of Neisseria meningitidis in human whole blood and mutagenesis studies identify virulence factors involved in blood survival. In: PLOS Pathogens, 2011, vol. 7, n° 5, p. e1002027. https://archive-ouverte.unige.ch/unige:25448

178 hits

29 downloads

Update

Deposited on : 2013-01-14

Export document
Format :
Citation style :