Project description:Microarray comparative genome hybridization (mCGH) data was collected from one Neisseria cinerea, two Neisseria lactamica, two Neisseria gonorrhoeae, and 48 Neisseria meningitidis isolates. For N. meningitidis, these isolates are from diverse clonal complexes, invasive and carriage strains, and all major serogroups. The microarray platform represented N. meningitidis strains MC58, Z2491, and FAM18 and N. gonorrhoeae FA1090.
Project description:Although usually a harmless colonizer of the human nasopharynx, Neisseria meningitidis (meningococcus) can spread to the blood stream and cause invasive disease. For survival in blood, N. meningitidis evades the complement system by expression of a polysaccharide capsule and surface proteins sequestering the complement regulator fH. Meningococcal strains are highly diverse and are categorized by their serogroup and multilocus sequence typing. The sequence type 41/44 clonal complex makes up a major proportion of serogroup B meningococcal disease worldwide, but it is also common in asymptomatic carriers. Proteome analysis of a serum resistant isolate from invasive meningococcal disease and two less resistant isolates from healthy carriers identified NspA as the sole protein consistently expressed more abundantly in the invasive isolate. Knock-out of nspA reduced serum resistance, accompanied by stronger deposition of membrane attack complex (C5b9). High or low expression of NspA was associated with sequence variation within a homopolymeric tract located in the -10/-35 region of the nspA promotor: A tract with 5 adenosines dictated low NspA expression, whereas a 6-adenosine motif led to high NspA expression. High levels of NspA correlated with high factor H sequestration onto the bacteria. We could not link the homopolymeric tract length to phase variation, unlike described for other N. meningitidis surface proteins with similar sequence motifs. Epidemiological evidence from carriage and disease isolates indicates that NspA contributes to serum resistance, but is not a prerequisite for invasive disease. Thus, the lineage ST-41/44 meningococcal strains are heterogenous in their NspA expression.
Project description:Neisseria meningitidis (meningococcus) is usually transmitted via respiratory droplets, whereas its close relative, the gonococcus is sexually transmitted. Invasive meningococcal disease due to isolates of serogroup C increased in Europe and the United States among men who have sex with men (MSM). These isolates were also recovered from cases of urethritis suggesting sexual transmission. Genome sequencing of representative strains revealed that isolates from MSM and urethritis cases belonged to a unique clade within clonal complex11. Proteome analysis showed expression of nitrite reductase by these isolates, enabling anaerobic growth as in gonococci. Invasive isolates from MSM, but not urethritis isolates expressed functional human factor H (hfH) binding protein associated with enhanced survival in transgenic mice expressing hfH, a complement regulatory protein. Our data provide a unique example of meningococcal evolution with adaptation to sexual transmissibility, initially associated with low virulence but with subsequent fHbp-associated invasiveness. Implications for vaccination strategies are discussed.
Project description:Streptococcus pneumoniae is a frequent coloniser of the human nasopharynx and a major cause of life-threating invasive infections such as pneumonia, meningitis and sepsis. Over 1 million people die every year due to invasive pneumococcal disease (IPD), mainly in developing countries. Serotype 1 is a common cause of IPD; however, unlike other serotypes, it is rarely found in the carrier state in the nasopharynx, which is often considered a prerequisite for disease. The aim of this study was to understand this dichotomy. We used murine models of carriage and IPD to characterise the pathogenesis of African serotype 1 (Sequence Type 217) pneumococcal strains obtained from the Queen Elizabeth Central Hospital in Blantyre, Malawi. We found that ST217 pneumococcal strains were highly virulent in a mouse model of invasive pneumonia, but in contrast to the generally accepted assumption, can also successfully establish nasopharyngeal carriage. Interestingly, we found that co-colonising serotypes may proliferate in the presence of serotype 1, suggesting that acquisition of serotype 1 carriage could increase the risk of developing IPD by other serotypes. RNAseq analysis confirmed that key virulence genes associated with inflammation and tissue invasiveness were upregulated in serotype 1. These data reveal important new insights into serotype 1 pathogenesis, with implications for carriage potential and risk of invasive disease through interactions with other co-colonising serotypes; an often overlooked factor in transmission and disease progression.
Project description:The Gram-negative bacterium Neisseria meningitidis causes meningitis in humans and has been demonstrated to manipulate or alter host signalling pathways during infection of the central nervous system. In this study, the phosphoproteome of an in vitro model of the blood-cerebrospinal fluid barrier was investigated during infection with the Neisseria meningitidis serogroup B (NmB) strain MC58 in presence and absence of the bacterial capsule. We show that the capsule deficient mutant has a higher impact on the phosphoproteome of the infected cells and identify potentially regulated pathways and cellular processes during infection.
Project description:Baart2007 - Genome-scale metabolic network of
Neisseria meningitidis (iGB555)
This model is described in the article:
Modeling Neisseria
meningitidis metabolism: from genome to metabolic fluxes.
Baart GJ, Zomer B, de Haan A, van
der Pol LA, Beuvery EC, Tramper J, Martens DE.
Genome Biol. 2007; 8(7): R136
Abstract:
BACKGROUND: Neisseria meningitidis is a human pathogen that
can infect diverse sites within the human host. The major
diseases caused by N. meningitidis are responsible for death
and disability, especially in young infants. In general, most
of the recent work on N. meningitidis focuses on potential
antigens and their functions, immunogenicity, and pathogenicity
mechanisms. Very little work has been carried out on Neisseria
primary metabolism over the past 25 years. RESULTS: Using the
genomic database of N. meningitidis serogroup B together with
biochemical and physiological information in the literature we
constructed a genome-scale flux model for the primary
metabolism of N. meningitidis. The validity of a simplified
metabolic network derived from the genome-scale metabolic
network was checked using flux-balance analysis in chemostat
cultures. Several useful predictions were obtained from in
silico experiments, including substrate preference. A minimal
medium for growth of N. meningitidis was designed and tested
successfully in batch and chemostat cultures. CONCLUSION: The
verified metabolic model describes the primary metabolism of N.
meningitidis in a chemostat in steady state. The genome-scale
model is valuable because it offers a framework to study N.
meningitidis metabolism as a whole, or certain aspects of it,
and it can also be used for the purpose of vaccine process
development (for example, the design of growth media). The flux
distribution of the main metabolic pathways (that is, the
pentose phosphate pathway and the Entner-Douderoff pathway)
indicates that the major part of pyruvate (69%) is synthesized
through the ED-cleavage, a finding that is in good agreement
with literature.
This model is hosted on
BioModels Database
and identified by:
MODEL1507180069.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.