GENOMIC COMPARISON OF A. ACTINOMYCETEMCOMITANS STRAINS
C Casey Chen, Associate Professor
University Of Southern California, Department Of Contracts And Grants, Los Angeles, Ca 90033
Grant 3R01DE012212-08S1 from National Institute Of Dental & Craniofacial Research
Abstract: This award is issued in response to Notice OD-09-060, Recovery Act Administrative Supplements Providing Summer Research Experiences for Students and Science Educators. It is hypothesized that the genomes of bacterial pathogens are comprised of a core gene pool and a flexible gene pool. The stable core gene pool is inherited clonally and is found in virtually every strain of a species. In contrast, the flexible pool contains genetic elements that are acquired by horizontal gene transfer (HGT). Individual bacterial strains have different constellations of flexible genes that are tailored to their specific life style. Genomic islands (GEIs) are large DNA blocks (10-100kbp) acquired by bacteria via HGT en bloc and constitute important components of the flexible gene pool of bacterial genome. The distinctions between pathogenic and non-pathogenic bacteria in some species have been explained by the acquisition of GEIs by pathogenic strains. Bacteria may also increase their virulence by genomic deletions. In some instances, genomic deletions eliminate inhibitors of virulence factors and allow a full expression of pathogenicity. The Gram-negative facultative bacillus Actinobacillus actinomycetemcomitans (Aa) is a major pathogen in human periodontitis. Individual clones of Aa appear to exhibit differing degrees of pathogenicity and might even employ different virulence mechanisms. Our laboratory has obtained preliminary evidence for the presence of GEIs and smaller genomic islets (of unknown functions) in diverse Aa strains. The insertions of GEIs and slets have lead to truncation and/or inactivation of genes in some Aa strains. Here we test the hypothesis that both GEIs/islets and genomic deletions are common in Aa strains. Furthermore, the gain and loss of genes may change the phenotypes and virulence of Aa. 4 Specific Aims are identified I) Perform genomic comparison of Aa isolates by DNA microarrays based on the sequenced Aa strain HK1651, II) identify non-HK1651 GEIs/islets in Aa by PCR genomic mapping followed by cloning and sequencing, III) Examine the expression of Aa GEIs/islets and their impact to the gene expression profiles of Aa, IV) Assess the stability of Aa genome over time by arrays. The research plan is expected to (i) generate a thorough catalogue of GEIs/islets and large DNA deletions in the genomes of diverse Aa strains, (ii) obtain evidence for the expression (and possibly the functions) of GEIs/islets, (iii) examine the gene expression profiles of Aa with or without the presence of GEIs/islets, (iv) obtain evidence for the genomic instability of Aa over short periods of time (years), (v) identify new candidate virulence factors of Aa and (vi) elucidate the genetic basis of the phenotype and virulence variations of Aa. The results are likely to further the progress in the field of periodontal disease pathogenesis
Keywords: A. actinomycetemcomitans; Actinobacillus actinomycetemcomitans; Bacillus; Bacillus (bacterium); Bacteria; Bacterial Genome; Bacterium actinomycetem comitans; Bacterium comitans; Cataloging; Catalogs; Chronic Periodontitis; Cloning; DNA; DNA Chips; DNA Microarray; DNA Microarray Chip; DNA Microchips; Deoxyribonucleic Acid; Disease; Disease Association; Disease Outcome; Disorder; Elements; Exhibits; Expression Profiling; Expression Signature; Gene Expression; Gene Inactivation; Gene Pool; Gene Silencing; Gene Transfer, Horizontal; Gene Transfer, Lateral; Genes; Genetic; Genome; Genome Instability; Genome, Bacterial; Genomic Instability; Genomic Islands; Genomic Islet; Genomics; Hereditary; Horizontal Gene Transfer; Human; Human, General; Individual; Inherited; Islet, Genomic; Laboratories; Lead; Life Style; Lifestyle; Man (Taxonomy); Man, Modern; Maps; Molecular Fingerprinting; Molecular Profiling; Parodontosis; Pathogenesis; Pathogenicity; Pathogenicity Factors; Pattern; Pb element; Periodontal Diseases; Periodontitis; Phenotype; Relative; Relative (related person); Research; Testing; Time; Variant; Variation; Virulence; Virulence Factors; base; disease/disorder; fitness; flexibility; genetic element; heavy metal Pb; heavy metal lead; improved; inhibitor; inhibitor/antagonist; islet; molecuar profile; molecular signature; mutant; pathogen; pathogenic bacteria; periodontal disorder; periodontium disease; periodontium disorder
Project start date: 2009-06-02
Project end date: 2010-05-31
Budget start date: 2-JUN-2009
Budget end date: 31-MAY-2010
3R01DE012212-08S1 (2009): $16300
Sponsored Links Excellgen http://Excellgen.com
GENOMIC COMPARISON OF A. ACTINOMYCETEMCOMITANS STRAINS
C Casey Chen, Associate Professor
University Of Southern California, Department Of Contracts And Grants, Los Angeles, Ca 90033
Grant 3R01DE012212-09S1 from National Institute Of Dental & Craniofacial Research
Abstract: It is hypothesized that the genomes of bacterial pathogens are comprised of a core gene pool and a flexible gene pool. The stable core gene pool is inherited clonally and is found in virtually every strain of a species. In contrast, the flexible pool contains genetic elements that are acquired by horizontal gene transfer (HGT). Individual bacterial strains have different constellations of flexible genes that are tailored to their specific life style. Genomic islands (GEIs) are large DNA blocks (10-100kbp) acquired by bacteria via HGT en bloc and constitute important components of the flexible gene pool of bacterial genome. The distinctions between pathogenic and non-pathogenic bacteria in some species have been explained by the acquisition of GEIs by pathogenic strains. Bacteria may also increase their virulence by genomic deletions. In some instances, genomic deletions eliminate inhibitors of virulence factors and allow a full expression of pathogenicity. The Gram-negative facultative bacillus Actinobacillus actinomycetemcomitans (Aa) is a major pathogen in human periodontitis. Individual clones of Aa appear to exhibit differing degrees of pathogenicity and might even employ different virulence mechanisms. Our laboratory has obtained preliminary evidence for the presence of GEIs and smaller genomic islets (of unknown functions) in diverse Aa strains. The insertions of GEIs and slets have lead to truncation and/or inactivation of genes in some Aa strains. Here we test the hypothesis that both GEIs/islets and genomic deletions are common in Aa strains. Furthermore, the gain and loss of genes may change the phenotypes and virulence of Aa. 4 Specific Aims are identified I) Perform genomic comparison of Aa isolates by DNA microarrays based on the sequenced Aa strain HK1651, II) identify non-HK1651 GEIs/islets in Aa by PCR genomic mapping followed by cloning and sequencing, III) Examine the expression of Aa GEIs/islets and their impact to the gene expression profiles of Aa, IV) Assess the stability of Aa genome over time by arrays. The research plan is expected to (i) generate a thorough catalogue of GEIs/islets and large DNA deletions in the genomes of diverse Aa strains, (ii) obtain evidence for the expression (and possibly the functions) of GEIs/islets, (iii) examine the gene expression profiles of Aa with or without the presence of GEIs/islets, (iv) obtain evidence for the genomic instability of Aa over short periods of time (years), (v) identify new candidate virulence factors of Aa and (vi) elucidate the genetic basis of the phenotype and virulence variations of Aa. The results are likely to further the progress in the field of periodontal disease pathogenesis
Keywords: A. actinomycetemcomitans; Actinobacillus actinomycetemcomitans; Bacillus; Bacillus (bacterium); Bacteria; Bacterial Genome; Bacterium actinomycetem comitans; Bacterium comitans; Cataloging; Catalogs; Chronic Periodontitis; Cloning; DNA; DNA Chips; DNA Microarray; DNA Microarray Chip; DNA Microchips; Deoxyribonucleic Acid; Disease; Disease Association; Disease Outcome; Disorder; Elements; Exhibits; Expression Profiling; Expression Signature; Gene Expression; Gene Inactivation; Gene Pool; Gene Silencing; Gene Transfer, Horizontal; Gene Transfer, Lateral; Genes; Genetic; Genome; Genome Instability; Genomic Instability; Genomic Islands; Genomic Islet; Genomics; Hereditary; Horizontal Gene Transfer; Human; Human, General; Individual; Inherited; Laboratories; Lead; Life Style; Lifestyle; Man (Taxonomy); Man, Modern; Maps; Molecular Fingerprinting; Molecular Profiling; Parodontosis; Pathogenesis; Pathogenicity; Pathogenicity Factors; Pattern; Pb element; Periodontal Diseases; Periodontitis; Phenotype; Relative; Relative (related person); Research; Testing; Time; Variant; Variation; Virulence; Virulence Factors; base; disease/disorder; fitness; flexibility; genetic element; heavy metal Pb; heavy metal lead; improved; inhibitor; inhibitor/antagonist; islet; molecuar profile; molecular signature; mutant; pathogen; pathogenic bacteria; periodontal disorder; periodontium disease; periodontium disorder
Project start date: 1999-01-01
Project end date: 2011-06-30
Budget start date: 1-JUL-2009
Budget end date: 30-JUN-2010
3R01DE012212-09S1 (2009): $78973
Grants awarded to C Casey Chen
GENOMIC COMPARISON OF A. ACTINOMYCETEMCOMITANS STRAINS
C Casey Chen, Associate Professor
University Of Southern California, Department Of Contracts And Grants, Los Angeles, Ca 90033
Grant 5R01DE012212-10 from National Institute Of Dental & Craniofacial Research
Abstract: It is hypothesized that the genomes of bacterial pathogens are comprised of a core gene pool and a flexible gene pool. The stable core gene pool is inherited clonally and is found in virtually every strain of a species. In contrast, the flexible pool contains genetic elements that are acquired by horizontal gene transfer (HGT). Individual bacterial strains have different constellations of flexible genes that are tailored to their specific life style. Genomic islands (GEIs) are large DNA blocks (10-100kbp) acquired by bacteria via HGT en bloc and constitute important components of the flexible gene pool of bacterial genome. The distinctions between pathogenic and non-pathogenic bacteria in some species have been explained by the acquisition of GEIs by pathogenic strains. Bacteria may also increase their virulence by genomic deletions. In some instances, genomic deletions eliminate inhibitors of virulence factors and allow a full expression of pathogenicity. The Gram-negative facultative bacillus Actinobacillus actinomycetemcomitans (Aa) is a major pathogen in human periodontitis. Individual clones of Aa appear to exhibit differing degrees of pathogenicity and might even employ different virulence mechanisms. Our laboratory has obtained preliminary evidence for the presence of GEIs and smaller genomic islets (of unknown functions) in diverse Aa strains. The insertions of GEIs and slets have lead to truncation and/or inactivation of genes in some Aa strains. Here we test the hypothesis that both GEIs/islets and genomic deletions are common in Aa strains. Furthermore, the gain and loss of genes may change the phenotypes and virulence of Aa. 4 Specific Aims are identified I) Perform genomic comparison of Aa isolates by DNA microarrays based on the sequenced Aa strain HK1651, II) identify non-HK1651 GEIs/islets in Aa by PCR genomic mapping followed by cloning and sequencing, III) Examine the expression of Aa GEIs/islets and their impact to the gene expression profiles of Aa, IV) Assess the stability of Aa genome over time by arrays. The research plan is expected to (i) generate a thorough catalogue of GEIs/islets and large DNA deletions in the genomes of diverse Aa strains, (ii) obtain evidence for the expression (and possibly the functions) of GEIs/islets, (iii) examine the gene expression profiles of Aa with or without the presence of GEIs/islets, (iv) obtain evidence for the genomic instability of Aa over short periods of time (years), (v) identify new candidate virulence factors of Aa and (vi) elucidate the genetic basis of the phenotype and virulence variations of Aa. The results are likely to further the progress in the field of periodontal disease pathogenesis
Keywords: A. actinomycetemcomitans; Actinobacillus actinomycetemcomitans; Bacillus; Bacillus (bacterium); Bacteria; Bacterial Genome; Bacterium actinomycetem comitans; Bacterium comitans; Cataloging; Catalogs; Chronic Periodontitis; Cloning; DNA; DNA Chips; DNA Microarray; DNA Microarray Chip; DNA Microchips; Deoxyribonucleic Acid; Disease; Disease Association; Disease Outcome; Disorder; Elements; Exhibits; Expression Profiling; Expression Signature; Gene Expression; Gene Inactivation; Gene Pool; Gene Silencing; Gene Transfer, Horizontal; Gene Transfer, Lateral; Genes; Genetic; Genome; Genome Instability; Genomic Instability; Genomic Islands; Genomic Islet; Genomics; Hereditary; Horizontal Gene Transfer; Human; Human, General; Individual; Inherited; Laboratories; Lead; Life Style; Lifestyle; Man (Taxonomy); Man, Modern; Maps; Molecular Fingerprinting; Molecular Profiling; Parodontosis; Pathogenesis; Pathogenicity; Pathogenicity Factors; Pattern; Pb element; Periodontal Diseases; Periodontitis; Phenotype; Relative; Relative (related person); Research; Testing; Time; Variant; Variation; Virulence; Virulence Factors; base; disease/disorder; fitness; flexibility; genetic element; heavy metal Pb; heavy metal lead; improved; inhibitor; inhibitor/antagonist; islet; molecuar profile; molecular signature; mutant; pathogen; pathogenic bacteria; periodontal disorder; periodontium disease; periodontium disorder
Project start date: 1999-01-01
Project end date: 2011-06-30
Budget start date: 1-JUL-2010
Budget end date: 30-JUN-2011
5R01DE012212-10 (2010): $369089
5R01DE012212-09 (2009): $372993