Genomic studies on bacterial pathogens 何漣漪 國立成功大學 微生物及免疫學研究所
Genomic studies on bacterial pathogens 何漣漪 國立成功大學 微生物及免疫學研究所
Types of bacterial infections Localized vs.systemic infections ● Acute vs.chronic or persistent infections ● Contagious vs.noncontagious infections Obligate vs.opportunistic pathogens Community vs.nosocomial infections Extracellular vs.intracellular pathogens
• Localized vs. systemic infections • Acute vs. chronic or persistent infections • Contagious vs. noncontagious infections • Obligate vs. opportunistic pathogens • Community vs. nosocomial infections • Extracellular vs. intracellular pathogens Types of bacterial infections
Approaches to bacterial pathogenesis ·Biochemical studies ·Genetic studies ·Genomic studies Functional genomics Comparative genomics Proteomics Bacterium-host interactions
• Biochemical studies • Genetic studies • Genomic studies Functional genomics Comparative genomics Proteomics • Bacterium-host interactions Approaches to bacterial pathogenesis
Applications of microbial genomes 1.Design of new antimicrobial agents and vaccines. Cegelski L,Marshall GR,Eldridge GR,and Hultgren SJ. 2008.The biology and future prospects of antivirulence nerapies.Nature Reviews Microbiology 6:17-26. 2 Development of high-throughput detection or diagnosis of microbial pathogens
Applications of microbial genomes 1. Design of new antimicrobial agents and vaccines. Cegelski L, Marshall GR, Eldridge GR, and Hultgren SJ. 2008. The biology and future prospects of antivirulence therapies. Nature Reviews Microbiology 6: 17-26. 2. Development of high-throughput detection or diagnosis of microbial pathogens
Staphyloxanthin Staphyloxanthin,the carotenoid pigment,acts as an anti- oxidant and helps the bacteria resist killing by the reactive oxygen species(ROS),such as O2-,H2O2 and HOCI,in neutrophils.Bacteria that lack this pigment grow normally, but are deficient in skin abscess formation. Liu GY et al.,J.Exp.Med.202,209 (2005) Early enzymatic steps in staphyloxanthin production resemble those for cholesterol biosynthesis.A cholesterol biosynthesis inhibitor blocks staphyloxanthin biosynthesis, resulting in colorless bacteria with diminished virulence that were cleared by the innate immune system Liu Cl et al.,Science 319,1391 (2008)
Staphyloxanthin, the carotenoid pigment, acts as an antioxidant and helps the bacteria resist killing by the reactive oxygen species (ROS), such as O2– , H2O2 and HOCl, in neutrophils. Bacteria that lack this pigment grow normally, but are deficient in skin abscess formation. Staphyloxanthin Liu GY et al., J. Exp. Med. 202, 209 (2005) Early enzymatic steps in staphyloxanthin production resemble those for cholesterol biosynthesis. A cholesterol biosynthesis inhibitor blocks staphyloxanthin biosynthesis, resulting in colorless bacteria with diminished virulence that were cleared by the innate immune system Liu CI et al., Science 319, 1391 (2008)
GOLD Genomes OnLine Database v 2.0 Contact: Last Update: Location Genomesonline May17,2008 www.genomesonline.org 797 126 Published Complete Genomes Search GOLD:3715 genome projects Metagenomes 90 1768 934 Archaeal Ongoing Genomes Bacterial Ongoing Genomes Eukaryotic Ongoing Genomes http://www.genomesonline.org/gold.cgi
http://www.genomesonline.org/gold.cgi
Genomes OnLine Database(GOLD)v.2 GOLDSTAMP Organism Size DATA Institution Project Status Contact Gc00007 H.pylori 1667Kb NC000915 26695 15760r6 J.Craig Venter Complete and MAP AE000511 Institute Published Tomb J正 Gi02776 H.pylori 35A BCM-HGSC targeted Weinstock G Gi02771 H.pylori 74B BCM-HGSC targeted Weinstock G Gi00295 H.pylori Uniy of Uppsala duodenal ulcer Karlinska Institut incomplete Gi00571 H.pylori Uniy of Uppsala gastric cancerl Karolinska Institute incomplete Gi00572 H.pylori Univ of Uppsala tric cancer2 Karolinska Institute incomplete 1596K Gc00390 NC008086 Washington Univ Complete and HPAGI 15360r MAP Published H.pylori Gi03002 Y438AG0( Washington Univ incomplete H.pylori Gi03001 X 438 CA4C Washington Univ incomplete 1 1643Kb Astra Gc00020 H.pylori NC000921 Complete and j99 14910r6 Genome Alm RA MAP AE001439 Therapeutics Published http://www.genomesonline.org/index.htm
Genomes OnLine Database (GOLD) v. 2 GOLDSTAMP Organism Size DATA Institution Project Status Contact Gc00007 H. pylori 26695 1667 Kb 1576 orfs MAP NC_000915 AE000511 J. Craig Venter Institute Complete and Published Tomb JF Gi02776 H. pylori 35A BCM-HGSC targeted Weinstock G Gi02777 H. pylori 74B BCM-HGSC targeted Weinstock G Gi00295 H. pylori duodenal ulcer Univ of Uppsala Karolinska Institute incomplete Gi00571 H. pylori gastric cancer1 Univ of Uppsala Karolinska Institute incomplete Gi00572 H. pylori gastric cancer2 Univ of Uppsala Karolinska Institute incomplete Gc00390 H. pylori HPAG1 1596 Kb 1536 orfs MAP NC_008086 Washington Univ Complete and Published Gi03002 H. pylori HPKX_438_AG0C 1 Washington Univ incomplete Gi03001 H. pylori HPKX_438_CA4C 1 Washington Univ incomplete Gc00020 H. pylori J99 1643 Kb 1491 orfs MAP NC_000921 AE001439 Astra Genome Therapeutics Complete and Published Alm RA http://www.genomesonline.org/index.htm
MINIREVIEW Ten years after the first Helicobacter pylori genome:comparative and functional genomics provide new insights in the variability and adaptability of a persistent pathogen Hilde de Reuse&Stefan Bereswill2 'Institut Pasteur,Unite de Pathogenie Bacterienne des Muqueuses,Paris,France:andInstitut for Mikrobiologie und Hygiene. Charite-Universitatsmedizin Berlin,Campus Charite Mitte,Berlin,Germany Correspondence:Stefan Bereswill Charite- Abstract Department of Microbiolgy and Hygiene. In this review,we summarize how genomic approaches contributed to the Campus Charite Mitte (C CM) understanding of the biology of the recently discovered pathogen Helicobacter DorotheenstraBe 96,D-10117 Berlin, pylori.Comparative genomics provided new insights into H.pylori's spectacular Germany.Tel.:+4930450524006: genetic diversity and generated exiting hypotheses on its evolutionary history. fax:+49450524904e-mait Transcriptomic studies provided original information on the mechanisms of stefan bereswillcharite de H.pylori gastric adaptation that are central to its virulence. FEMS Immunol Med Microbiol 50(2007)165-176
FEMS Immunol Med Microbiol 50 (2007) 165–176
Comparative genomics Helicobacter pylori diversity at the genome level Definition of the core genome and the variable gene pool Identification of strain-,species-and genus-specific genes Worldwide coevolution and spreading with the human host (by Multi Locus Sequence Typing,MLST) Microevolution and genetic variability within single human hosts H.pylori evolution during early infection and disease progression FEMS Immunol Med Microbiol 50(2007)165-176
Comparative genomics Helicobacter pylori diversity at the genome level Definition of the core genome and the variable gene pool Identification of strain-, species- and genus-specific genes Worldwide coevolution and spreading with the human host (by Multi Locus Sequence Typing, MLST) Microevolution and genetic variability within single human hosts H. pylori evolution during early infection and disease progression FEMS Immunol Med Microbiol 50 (2007) 165–176
Functional genomics Transcriptome analysis in conditions mimicking those encountered in the host (acidity,growth phase,iron starvation and attachment to gastric cells) Transcriptome analysis in mutants deficient in regulators (eg.Ars,Fur,o28,o54) Transcriptome analysis in mutants deficient in regulators in response to acidity and metal metabolism FEMS Immunol Med Microbiol 50(2007)165-176
Functional genomics Transcriptome analysis in conditions mimicking those encountered in the host (acidity, growth phase, iron starvation and attachment to gastric cells) Transcriptome analysis in mutants deficient in regulators (eg. Ars, Fur, s 28 , s 54) Transcriptome analysis in mutants deficient in regulators in response to acidity and metal metabolism FEMS Immunol Med Microbiol 50 (2007) 165–176