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Identification of potential therapeutic targets for Burkholderia cenocepacia by comparative transcriptomics.

Yoder-Himes DR, Konstantinidis KT, Tiedje JM - PLoS ONE (2010)

Bottom Line: Conservation of these induced genes was established using the 11 available Bcc genome sequences to indicate whether potential therapeutic targets would be species-wide.Comparative transcriptomics is a useful way to identify new potential virulence factors and therapeutic targets for pathogenic bacteria.We identified eight genes induced under CF conditions that were also conserved in the Bcc and may constitute particularly attractive therapeutic targets due to their signal sequence, predicted cellular location, and homology to known therapeutic targets.

View Article: PubMed Central - PubMed

Affiliation: Center for Microbial Ecology, Michigan State University, East Lansing, Michigan, United States of America.

ABSTRACT

Background: Burkholderia cenocepacia is an endemic soil dweller and emerging opportunistic pathogen in patients with cystic fibrosis (CF). The identification of virulence factors and potential therapeutic targets has been hampered by the genomic diversity within the species as many factors are not shared among the pathogenic members of the species.

Methodology/principal findings: In this study, global identification of putative virulence factors was performed by analyzing the transcriptome of two related strains of B. cenocepacia (one clinical, one environmental) under conditions mimicking cystic fibrosis sputum versus soil. Soil is a natural reservoir for this species; hence, genes induced under CF conditions relative to soil may represent adaptations that have occurred in clinical strains. Under CF conditions, several genes encoding proteins thought to be involved in virulence were induced and many new ones were identified. Our analysis, in combination with previous studies, reveals 458 strain-specific genes, 126 clinical-isolate-specific, and at least four species-specific genes that are induced under CF conditions. The chromosomal distribution of the induced genes was disproportionate to the size of the chromosome as genes expressed under soil conditions by both strains were more frequent on the second chromosome and those differentially regulated between strains were more frequent on the third chromosome. Conservation of these induced genes was established using the 11 available Bcc genome sequences to indicate whether potential therapeutic targets would be species-wide.

Conclusions/significance: Comparative transcriptomics is a useful way to identify new potential virulence factors and therapeutic targets for pathogenic bacteria. We identified eight genes induced under CF conditions that were also conserved in the Bcc and may constitute particularly attractive therapeutic targets due to their signal sequence, predicted cellular location, and homology to known therapeutic targets.

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Distribution of J2315 genes, HI2424 homologous genes, and genes induced in J2315 compared to HI2424.Heat map analysis reveals gene clusters induced in J2315 compared to HI2424 under CF conditions that are shared (shown in the middle lane) or unique to J2315. Open reading frames in HI2424 bearing at least 70% identity over 70% of the length were considered homologous to J2315 genes. Red color indicates present/induced and gray indicates absent/not induced.
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pone-0008724-g004: Distribution of J2315 genes, HI2424 homologous genes, and genes induced in J2315 compared to HI2424.Heat map analysis reveals gene clusters induced in J2315 compared to HI2424 under CF conditions that are shared (shown in the middle lane) or unique to J2315. Open reading frames in HI2424 bearing at least 70% identity over 70% of the length were considered homologous to J2315 genes. Red color indicates present/induced and gray indicates absent/not induced.

Mentions: An examination of the 1490 protein-encoding genes induced over 2-fold in J2315 revealed that 751 of them were present in the HI2424 genome suggesting that the regulation of these “core” genes had changed since the two strains diverged (Fig. 4). The other 739 genes were not found in the HI2424 genome and these genes were typically found in small clusters, i.e, genomic islands, on all three chromosomes (Fig. 4).These 739 genes may represent recent acquisitions by J2315 since over 50% of these genes (430) were annotated as hypothetical proteins (Table S3). Also among these genes were 21 genes corresponding to phage structural genes and more than 30 transposon- and integrase-associated genes, features consistent with genes frequently transferred horizontally among bacteria.


Identification of potential therapeutic targets for Burkholderia cenocepacia by comparative transcriptomics.

Yoder-Himes DR, Konstantinidis KT, Tiedje JM - PLoS ONE (2010)

Distribution of J2315 genes, HI2424 homologous genes, and genes induced in J2315 compared to HI2424.Heat map analysis reveals gene clusters induced in J2315 compared to HI2424 under CF conditions that are shared (shown in the middle lane) or unique to J2315. Open reading frames in HI2424 bearing at least 70% identity over 70% of the length were considered homologous to J2315 genes. Red color indicates present/induced and gray indicates absent/not induced.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2806911&req=5

pone-0008724-g004: Distribution of J2315 genes, HI2424 homologous genes, and genes induced in J2315 compared to HI2424.Heat map analysis reveals gene clusters induced in J2315 compared to HI2424 under CF conditions that are shared (shown in the middle lane) or unique to J2315. Open reading frames in HI2424 bearing at least 70% identity over 70% of the length were considered homologous to J2315 genes. Red color indicates present/induced and gray indicates absent/not induced.
Mentions: An examination of the 1490 protein-encoding genes induced over 2-fold in J2315 revealed that 751 of them were present in the HI2424 genome suggesting that the regulation of these “core” genes had changed since the two strains diverged (Fig. 4). The other 739 genes were not found in the HI2424 genome and these genes were typically found in small clusters, i.e, genomic islands, on all three chromosomes (Fig. 4).These 739 genes may represent recent acquisitions by J2315 since over 50% of these genes (430) were annotated as hypothetical proteins (Table S3). Also among these genes were 21 genes corresponding to phage structural genes and more than 30 transposon- and integrase-associated genes, features consistent with genes frequently transferred horizontally among bacteria.

Bottom Line: Conservation of these induced genes was established using the 11 available Bcc genome sequences to indicate whether potential therapeutic targets would be species-wide.Comparative transcriptomics is a useful way to identify new potential virulence factors and therapeutic targets for pathogenic bacteria.We identified eight genes induced under CF conditions that were also conserved in the Bcc and may constitute particularly attractive therapeutic targets due to their signal sequence, predicted cellular location, and homology to known therapeutic targets.

View Article: PubMed Central - PubMed

Affiliation: Center for Microbial Ecology, Michigan State University, East Lansing, Michigan, United States of America.

ABSTRACT

Background: Burkholderia cenocepacia is an endemic soil dweller and emerging opportunistic pathogen in patients with cystic fibrosis (CF). The identification of virulence factors and potential therapeutic targets has been hampered by the genomic diversity within the species as many factors are not shared among the pathogenic members of the species.

Methodology/principal findings: In this study, global identification of putative virulence factors was performed by analyzing the transcriptome of two related strains of B. cenocepacia (one clinical, one environmental) under conditions mimicking cystic fibrosis sputum versus soil. Soil is a natural reservoir for this species; hence, genes induced under CF conditions relative to soil may represent adaptations that have occurred in clinical strains. Under CF conditions, several genes encoding proteins thought to be involved in virulence were induced and many new ones were identified. Our analysis, in combination with previous studies, reveals 458 strain-specific genes, 126 clinical-isolate-specific, and at least four species-specific genes that are induced under CF conditions. The chromosomal distribution of the induced genes was disproportionate to the size of the chromosome as genes expressed under soil conditions by both strains were more frequent on the second chromosome and those differentially regulated between strains were more frequent on the third chromosome. Conservation of these induced genes was established using the 11 available Bcc genome sequences to indicate whether potential therapeutic targets would be species-wide.

Conclusions/significance: Comparative transcriptomics is a useful way to identify new potential virulence factors and therapeutic targets for pathogenic bacteria. We identified eight genes induced under CF conditions that were also conserved in the Bcc and may constitute particularly attractive therapeutic targets due to their signal sequence, predicted cellular location, and homology to known therapeutic targets.

Show MeSH
Related in: MedlinePlus