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Mining virulence genes using metagenomics.

Belda-Ferre P, Cabrera-Rubio R, Moya A, Mira A - PLoS ONE (2011)

Bottom Line: When a bacterial genome is compared to the metagenome of an environment it inhabits, most genes recruit at high sequence identity.From an applied point of view, MIs of human pathogens (e.g. those identified in enterohaemorragic Escherichia coli against the gut metagenome or in pathogenic Neisseria meningitidis against the oral metagenome) include virulence genes that appear to be absent in related strains or species present in the microbiome of healthy individuals.Using this approach, we detect well-known pathogenicity islands and identify new potential virulence genes in several human pathogens.

View Article: PubMed Central - PubMed

Affiliation: Joint Unit of Research in Genomics and Health, Centre for Public Health Research-Cavanilles Institute for Biodiversity and Evolutionary Biology, University of Valencia, Valencia, Spain.

ABSTRACT
When a bacterial genome is compared to the metagenome of an environment it inhabits, most genes recruit at high sequence identity. In free-living bacteria (for instance marine bacteria compared against the ocean metagenome) certain genomic regions are totally absent in recruitment plots, representing therefore genes unique to individual bacterial isolates. We show that these Metagenomic Islands (MIs) are also visible in bacteria living in human hosts when their genomes are compared to sequences from the human microbiome, despite the compartmentalized structure of human-related environments such as the gut. From an applied point of view, MIs of human pathogens (e.g. those identified in enterohaemorragic Escherichia coli against the gut metagenome or in pathogenic Neisseria meningitidis against the oral metagenome) include virulence genes that appear to be absent in related strains or species present in the microbiome of healthy individuals. We propose that this strategy (i.e. recruitment analysis of pathogenic bacteria against the metagenome of healthy subjects) can be used to detect pathogenicity regions in species where the genes involved in virulence are poorly characterized. Using this approach, we detect well-known pathogenicity islands and identify new potential virulence genes in several human pathogens.

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Comparing healthy microbiomes against bacterial genomes.Metagenomic recruitment of (A) the gut metagenome against the three enteric human pathogens S. flexneri. E. coli ETEC and E. coli CFT073; (B) the gut metagenome against the avirulent E. coli K12 laboratory strain; and (C) the dental plaque metagenome against twoe pathogenic neisserial species. Some relevant pathogenicity islands are indicated (for a full list of MIs gene content see Table S1). The few islands detected in the commensal E. coli K12 strain correspond to mobile genetic elements, mainly phage genes, as well as a few outer membrane genes.
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pone-0024975-g001: Comparing healthy microbiomes against bacterial genomes.Metagenomic recruitment of (A) the gut metagenome against the three enteric human pathogens S. flexneri. E. coli ETEC and E. coli CFT073; (B) the gut metagenome against the avirulent E. coli K12 laboratory strain; and (C) the dental plaque metagenome against twoe pathogenic neisserial species. Some relevant pathogenicity islands are indicated (for a full list of MIs gene content see Table S1). The few islands detected in the commensal E. coli K12 strain correspond to mobile genetic elements, mainly phage genes, as well as a few outer membrane genes.

Mentions: Similarly to free-living bacteria, when metagenomic recruitments are made between the genomes of gut-associated bacteria against the human gut metagenome, regions with low or absent recruitment are clearly visible (Figure 1A). This shows that gut inhabitants also have genomic regions that appear to be unique to individual strains. In free-living habitats like aquatic environments, intraspecific genomic diversification has been proposed as a strategy to exploit different microniches [8], and this would partly account for differences in gene content among strains from the same species. In the gut and other host-related environments, the confinement of bacteria to a given host individual, with limited microbial exchange through the faecal-oral route, imposes a compartmentalized structure to these niches, which may contribute to the observed differences in genomic content between strains. However, the appearance of MIs could also be showing genes specific to virulent strains because recruitment plots for commensal bacteria displayed a higher coverage along the genome and a limited presence of MIs (Fig. 1B), which were limited to mobile genetic elements, mainly phage genes (48.8% of the total) and several outer membrane proteins (14.6% of the total). Thus, in order to determine whether regions of absent recruitment identify genes involved in pathogenicity, we performed a systematic description of gene content in MIs from human pathogens for which pathogenicity islands and virulence genes are well characterized.


Mining virulence genes using metagenomics.

Belda-Ferre P, Cabrera-Rubio R, Moya A, Mira A - PLoS ONE (2011)

Comparing healthy microbiomes against bacterial genomes.Metagenomic recruitment of (A) the gut metagenome against the three enteric human pathogens S. flexneri. E. coli ETEC and E. coli CFT073; (B) the gut metagenome against the avirulent E. coli K12 laboratory strain; and (C) the dental plaque metagenome against twoe pathogenic neisserial species. Some relevant pathogenicity islands are indicated (for a full list of MIs gene content see Table S1). The few islands detected in the commensal E. coli K12 strain correspond to mobile genetic elements, mainly phage genes, as well as a few outer membrane genes.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198465&req=5

pone-0024975-g001: Comparing healthy microbiomes against bacterial genomes.Metagenomic recruitment of (A) the gut metagenome against the three enteric human pathogens S. flexneri. E. coli ETEC and E. coli CFT073; (B) the gut metagenome against the avirulent E. coli K12 laboratory strain; and (C) the dental plaque metagenome against twoe pathogenic neisserial species. Some relevant pathogenicity islands are indicated (for a full list of MIs gene content see Table S1). The few islands detected in the commensal E. coli K12 strain correspond to mobile genetic elements, mainly phage genes, as well as a few outer membrane genes.
Mentions: Similarly to free-living bacteria, when metagenomic recruitments are made between the genomes of gut-associated bacteria against the human gut metagenome, regions with low or absent recruitment are clearly visible (Figure 1A). This shows that gut inhabitants also have genomic regions that appear to be unique to individual strains. In free-living habitats like aquatic environments, intraspecific genomic diversification has been proposed as a strategy to exploit different microniches [8], and this would partly account for differences in gene content among strains from the same species. In the gut and other host-related environments, the confinement of bacteria to a given host individual, with limited microbial exchange through the faecal-oral route, imposes a compartmentalized structure to these niches, which may contribute to the observed differences in genomic content between strains. However, the appearance of MIs could also be showing genes specific to virulent strains because recruitment plots for commensal bacteria displayed a higher coverage along the genome and a limited presence of MIs (Fig. 1B), which were limited to mobile genetic elements, mainly phage genes (48.8% of the total) and several outer membrane proteins (14.6% of the total). Thus, in order to determine whether regions of absent recruitment identify genes involved in pathogenicity, we performed a systematic description of gene content in MIs from human pathogens for which pathogenicity islands and virulence genes are well characterized.

Bottom Line: When a bacterial genome is compared to the metagenome of an environment it inhabits, most genes recruit at high sequence identity.From an applied point of view, MIs of human pathogens (e.g. those identified in enterohaemorragic Escherichia coli against the gut metagenome or in pathogenic Neisseria meningitidis against the oral metagenome) include virulence genes that appear to be absent in related strains or species present in the microbiome of healthy individuals.Using this approach, we detect well-known pathogenicity islands and identify new potential virulence genes in several human pathogens.

View Article: PubMed Central - PubMed

Affiliation: Joint Unit of Research in Genomics and Health, Centre for Public Health Research-Cavanilles Institute for Biodiversity and Evolutionary Biology, University of Valencia, Valencia, Spain.

ABSTRACT
When a bacterial genome is compared to the metagenome of an environment it inhabits, most genes recruit at high sequence identity. In free-living bacteria (for instance marine bacteria compared against the ocean metagenome) certain genomic regions are totally absent in recruitment plots, representing therefore genes unique to individual bacterial isolates. We show that these Metagenomic Islands (MIs) are also visible in bacteria living in human hosts when their genomes are compared to sequences from the human microbiome, despite the compartmentalized structure of human-related environments such as the gut. From an applied point of view, MIs of human pathogens (e.g. those identified in enterohaemorragic Escherichia coli against the gut metagenome or in pathogenic Neisseria meningitidis against the oral metagenome) include virulence genes that appear to be absent in related strains or species present in the microbiome of healthy individuals. We propose that this strategy (i.e. recruitment analysis of pathogenic bacteria against the metagenome of healthy subjects) can be used to detect pathogenicity regions in species where the genes involved in virulence are poorly characterized. Using this approach, we detect well-known pathogenicity islands and identify new potential virulence genes in several human pathogens.

Show MeSH
Related in: MedlinePlus