ArticlePLoS pathogens2011
Transcriptome analysis of Neisseria meningitidis in human whole blood and mutagenesis studies identify virulence factors involved in blood survival.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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88 citing papers in PubMed, 144 citations in OpenAlex.
- Microevolution of Neisseria lactamica during nasopharyngeal colonisation induced by controlled human infection.Nature communications · 2018Trial
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- Streptococcal arginine deiminase system defences macrophage bactericidal effect mediated by XRE family protein XtrSs.Virulence · 2024Article
- Deep learning-based characterization of neutrophil activation phenotypes inComputational and structural biotechnology journal · 2024Article
- Metatranscriptomic insights into the dengue patient blood microbiome: Enhanced microbial diversity and metabolic activity in severe patients.PLoS neglected tropical diseases · 2024Article
- Determinants of bacterial survival and proliferation in blood.FEMS microbiology reviews · 2024Review
- Classification ofiScience · 2024Article
- Biochemical and structural characterization of meningococcal methylenetetrahydrofolate reductase.Protein science : a publication of the Protein Society · 2023Article
- OpcA and PorB are novel bactericidal antigens of the 4CMenB vaccine in mice and humans.NPJ vaccines · 2023Article
- Broad-spectrum in vitro activity of macrophage infectivity potentiator inhibitors against Gram-negative bacteria and Leishmania major.The Journal of antimicrobial chemotherapy · 2022Article
- Neisseria genes required for persistence identified via in vivo screening of a transposon mutant library.PLoS pathogens · 2022Article
- Automated characterisation of neutrophil activation phenotypes inComputational and structural biotechnology journal · 2022Article
- Update on theFrontiers in cellular and infection microbiology · 2022Review
- Deconvolution of intergenic polymorphisms determining high expression of Factor H binding protein in meningococcus and their association with invasive disease.PLoS pathogens · 2021Article
- Anti-Virulence Therapeutic Approaches forAntibiotics (Basel, Switzerland) · 2021Review
- Omics Analysis of Blood-Responsive Regulon inInternational journal of molecular sciences · 2021Article
- The Novel Streptococcal Transcriptional Regulator XtgS Negatively Regulates Bacterial Virulence and Directly Represses PseP Transcription.Infection and immunity · 2020Article
- Meningococcal core and accessory phasomes vary by clonal complex.Microbial genomics · 2020Article
- In vitro immune responses of human PBMCs against Candida albicans reveals fungal and leucocyte phenotypes associated with fungal persistence.Scientific reports · 2020Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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