The analysis of <b><i>Neisseria meningitidis</i></b> proteomes: Reference maps and their applications

Bernardini, Giulia; Braconi, Daniela; Santucci, Annalisa

doi:10.1002/pmic.200700094

Cited by 16 publications

(9 citation statements)

References 90 publications

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“…Since dedicated metabolic measurements such as isotopolog profiling under infection condition have not been carried out in meningococci so far, most information on the relation between metabolism and virulence is thus indirect and stems mostly from “omic” technologies such as (comparative) genomics (Dunning Hotopp et al, 2006; Rusniok et al, 2009; Hao et al, 2011; Joseph et al, 2011), transcriptomics (Grifantini et al, 2002a,b; Dietrich et al, 2003; Joseph et al, 2010; Echenique-Rivera et al, 2011; Hedman et al, 2012; Hey et al, 2013), proteomics (Bernardini et al, 2007; Van Alen et al, 2010) and genome-wide signature-tagged mutagenesis (STM) (Sun et al, 2000; Mendum et al, 2011) in conjunction with metabolic modeling (Baart et al, 2007). Therefore, after providing a very short overview of the metabolic capabilities of N. meningitidis derived in large part from genome-based approaches, we will discuss data also derived mostly from different “omic” approaches addressing the role of meningococcal core metabolism in the context of meningococcal colonization and invasion of host tissues.…”

Section: Introductionmentioning

confidence: 99%

Metabolism and virulence in Neisseria meningitidis

Schoen

Kischkies

Elias

et al. 2014

Front. Cell. Infect. Microbiol.

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A longstanding question in infection biology addresses the genetic basis for invasive behavior in commensal pathogens. A prime example for such a pathogen is Neisseria meningitidis. On the one hand it is a harmless commensal bacterium exquisitely adapted to humans, and on the other hand it sometimes behaves like a ferocious pathogen causing potentially lethal disease such as sepsis and acute bacterial meningitis. Despite the lack of a classical repertoire of virulence genes in N. meningitidis separating commensal from invasive strains, molecular epidemiology suggests that carriage and invasive strains belong to genetically distinct populations. In recent years, it has become increasingly clear that metabolic adaptation enables meningococci to exploit host resources, supporting the concept of nutritional virulence as a crucial determinant of invasive capability. Here, we discuss the contribution of core metabolic pathways in the context of colonization and invasion with special emphasis on results from genome-wide surveys. The metabolism of lactate, the oxidative stress response, and, in particular, glutathione metabolism as well as the denitrification pathway provide examples of how meningococcal metabolism is intimately linked to pathogenesis. We further discuss evidence from genome-wide approaches regarding potential metabolic differences between strains from hyperinvasive and carriage lineages and present new data assessing in vitro growth differences of strains from these two populations. We hypothesize that strains from carriage and hyperinvasive lineages differ in the expression of regulatory genes involved particularly in stress responses and amino acid metabolism under infection conditions.

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Section: Introductionmentioning

confidence: 99%

Metabolism and virulence in Neisseria meningitidis

Schoen

Kischkies

Elias

et al. 2014

Front. Cell. Infect. Microbiol.

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“…In the present study, soluble proteins of two rifampicin resistant and one susceptible meningococci isolated in Italy, and previously described [5], were analysed by two-dimensional electrophoresis (2-DE) combined with mass spectrometry (MALDI-ToF). The method has been chosen because it is a comprehensive approach to investigate the protein content of a pathogen [12], and in this context helpful to identify differential expression in specific proteins in particular in rifampicin resistance meningococci.…”

Section: Introductionmentioning

confidence: 99%

Neisseria meningitidis rifampicin resistant strains: analysis of protein differentially expressed

et al. 2010

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BackgroundSeveral mutations have been described as responsible for rifampicin resistance in Neisseria meningitidis. However, the intriguing question on why these strains are so rare remains open. The aim of this study was to investigate the protein content and to identify differential expression in specific proteins in two rifampicin resistant and one susceptible meningococci using two-dimensional electrophoresis (2-DE) combined with mass spectrometry.ResultsIn our experimental conditions, able to resolve soluble proteins with an isoelectric point between 4 and 7, twenty-three proteins have been found differentially expressed in the two resistant strains compared to the susceptible. Some of them, involved in the main metabolic pathways, showed an increased expression, mainly in the catabolism of pyruvate and in the tricarboxylic acid cycle. A decreased expression of proteins belonging to gene regulation and to those involved in the folding of polypeptides has also been observed. 2-DE analysis showed the presence of four proteins displaying a shift in their isoelectric point in both resistant strains, confirmed by the presence of amino acid changes in the sequence analysis, absent in the susceptible.ConclusionsThe analysis of differentially expressed proteins suggests that an intricate series of events occurs in N. meningitidis rifampicin resistant strains and the results here reported may be considered a starting point in understanding their decreased invasion capacity. In fact, they support the hypothesis that the presence of more than one protein differentially expressed, having a role in the metabolism of the meningococcus, influences its ability to infect and to spread in the population. Different reports have described and discussed how a drug resistant pathogen shows a high biological cost for survival and that may also explain why, for some pathogens, the rate of resistant organisms is relatively low considering the widespread use of a particular drug. This seems the case of rifampicin resistant meningococci.

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“…The increasing knowledge regarding highly immunoreactive antigens offers useful information for further investigation of potential associations between specific immune responses and diseases (91)(92)(93)(94). In addition, the comparison of multiple immunoproteomes may allow the discovery of immunogenic structural features shared and conserved between different pathogens, which could form the basis of broadly protective multispecies vaccines.…”

Section: Immunomics: Identification Of Immunogenic Proteinsmentioning

confidence: 99%

Vaccinology in the genome era

Rinaudo¹,

Telford²,

Rappuoli³

et al. 2009

J. Clin. Invest.

144

118

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Vaccination has played a significant role in controlling and eliminating life-threatening infectious diseases throughout the world, and yet currently licensed vaccines represent only the tip of the iceberg in terms of controlling human pathogens. However, as we discuss in this Review, the arrival of the genome era has revolutionized vaccine development and catalyzed a shift from conventional culture-based approaches to genome-based vaccinology. The availability of complete bacterial genomes has led to the development and application of high-throughput analyses that enable rapid targeted identification of novel vaccine antigens. Furthermore, structural vaccinology is emerging as a powerful tool for the rational design or modification of vaccine antigens to improve their immunogenicity and safety.

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The analysis of Neisseria meningitidis proteomes: Reference maps and their applications

Cited by 16 publications

References 90 publications

Metabolism and virulence in Neisseria meningitidis

Metabolism and virulence in Neisseria meningitidis

Neisseria meningitidis rifampicin resistant strains: analysis of protein differentially expressed

Vaccinology in the genome era

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