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Bapuji Institute of Engineering and Technology,
DAVANGERE
Presented by,
Lakshmi kavya
Mounika P. V. R.
Ranjana Nagendra
Jinu D'Souza
Contents
1 Introduction
2 Identification of virulence factors
3 Fungal Pathogenomics
4 Bacterial Pathogenomics
5 Pathogenomics in its applied trends
6 Future trends and challenges
7 Pathogenomics in drug design
8 Conclusion
9 References
INTRODUCTION
 Pathogenic infections leads to increase in morbidity and
mortality rate in human and animal population.
 Pathogenomics attempts to
utilize genomics and metagenomics data from high through-put
technologies.
 The prevention and treatment of infectious diseases has posed a
medical challenge to the researchers.
Contd...
• Pathogenomics applies the newly gained knowledge to
treat and prevent disease.
• With the Functional Genomics, we can reveal the
pathogenesis-related genes.
•The research promotes the development of drugs,
diagnostic tools and vaccines .
•Comparative Genomics has gained more applicability with
the recent increased amount of sequence information.
IDENTIFICATION OF
VIRULENCE FACTORS
Direct Sequence Annotation Tools for
Functional Genomics:
 The first is the identification of transcripts and the
determination of reading frames using programs such as
Genscan and Gene predict.
 The next step is to analyse the mRNA including the
identification of regulatory elements, using an RNA analyser ,it
identifies individual regulatory elements in a RNA sequence
using a decision tree and executes sequence and secondary
structure searches for various elements.
Genome Analysis of pathogens as a
basis for Pharmacogenomic
strategies:
• Current methods allow collection of data on a genomic scale
involving the complete genome sequence , an overview of the
transcriptomes (by EST) and insight into the proteomes.
• The available genome sequences of various pathogens provide a
wide range of novel gene targets for drug design which can be
identified using microarray analysis.
Contd…
•Detailed analysis of gene expression by software such
as Bioconductor and R allows prediction about
activated or repressed genes, gene clusters, groups, and
pathways in pathogens.
• Analysis of all involved pathogen genes and the
interacting host genes, enzymes, and pathways by the
application of methods such as Pathway alignment and
elementary mode analysis.
Fig: Depicting Salmonella’s virulence factors
FUNGAL PATHOGENOMICS
 It occurs to recognise respond and persevere against the
invasive infection .
 Many chronic air way diseases such as allergy, asthma and
various forms of sinusitis are the result of both deleterious
alterations in airway functionality and overzealous innate
and adaptive response leading to chronic inflammation .
Contd…
•Alternaria has been associated with chronic respiratory
diseases such as IgE-dependent mold allergy, asthma, chronic
sinusitis and other allergic airway diseases.
• Novel therapeutic strategies, new diagnostics, drug targets
and medicine are being developed to reduce the impact of
ubiquitous fungi on the plant earth.
•In 2004, the NSF-VSDA Interagency Microbial Genome
Sequencing Program founded the project entitle. “The genome
sequence of the model mesotropic fungus, Alternaria
brassicicola”.
Contd…
•A project team was assembled at the Virginia Bioinformatics
Institute[VBI] who played a major role in human genome
project.
•This team had worked on whole genome shot gun sequencing,
BAC library construction Express Sequence Tag[EST]
sequencing, database development, genome annotation, and
unique transcript profiling technologies.
Fig: Alternaria spore
BACTERIAL
PATHOGENOMICS
 The horizontal gene transfer and genome decay .
 In Genome dynamics, three main forces have been found to
shape genomic evolution, gene gain, gene loss and gene
change.
 1. Some genetically uniform lineages have emerged recently in
evolutionary terms[ex. Bacillus anthracis and Mycobacterium
leprae].
 2.The recombination can occur between closely related
sequences in closely relating strains [ex. Neisseria mehingitedis
, hemophylus influenza].
Contd…
•3. Wide spread horizontal gene transfer .[ex. many enterobacteria and
some staphylococci].
•The whole genome sequencing has been used to detect SNPs.
•Genome sequencing also conforms that phase variation is a wide spread
source of inter specific genotypic and phenotypic variations.
• Horizontal gene transfer may be defined as transfer of genes or genome
from one cell to another cell of the same generation.
Fig: Bacterial genome dynamics
Comparative patho-genomics of
bacteria causing infectious
diseases in fish:
•The genome sequencing has uncovered evolutionary stratergies
mediated by horizontal gene transfer, insertional sequence elements,
mutations and prophage sequence present in fish pathogens.
• The genomes of bacteria are made up of circular or linear
chromosomes, extra chromosomal linear or circular plasmids .The
genes located on the “core” part of the chromosome exhibit a
relatively uniform G+C content end a specific codon usage.
Contd…
•Bacteria Vibrio are mainly pathogenic to marine and brackish water
fish.
•Vibriosis, one of the major bacterial diseases is mainly caused by
pathogenic species such as Vibrio anguillarum and V.ordalii.
•The 96F strain has a type3 secretion system[T3SS2],which is absent
in the 775 strain . In the 775 strain three transposase genes are present
at the T3SS2 chromosomal location, one of which probably originated
from the pJM1,indicating that the gene cluster is in activated by a
transposition, deletion, or inversion event.
•A striking feature of V.ordalii genome is its significant reduction in
size[3.4Mb] compare to the V.anguillarum strain775[4.1Mb].
•V.ordalii lacks the ABC transporter genes, the type6 secretion systems
and the genes for microbial collagensase.
PATHOGENICS IN ITS
APPLIED TRENDS
 To study life-threatening human pathogens.
 The analysis of the gene pools of pathogenic bacteria
including antigenic diversity and antigenic variation results in
more effective vaccines and vaccine implementation programs.
 The metabolism of the pathogen in the host allows the
identification of new targets for anti-infectives and therapeutic
approaches.
 The study of multiple pathogenic and non-pathogenic
microbes interacting in the host will improve the management
of multiple infections and will allow probiotic and prebiotic
interventions.
FUTURE TRENDS AND
CHALLENGES
 Nearly 25% of the annual deaths worldwide are directly related
to pathogens multidrug- resistant tuberculosis and HIV/AIDS
are on the rise worldwide; and Staphylococcus and
Enterococcus strains in Western hospitals are becoming
increasingly resistant to antibiotics.
 Scientific information could be misused for bioterrorism .
Contd…
•In vivo expression analyses and new bio-imaging techniques
now enable scientists to investigate the role of individual
genes during infection in real time.
•The World Health Organization (WHO) in 2004,
accordingly addressed the need for action plans to counteract
potential bioterrorist attacks; indeed there is no such
international body till date to investigate the sudden
emergence of infectious diseases.
PATHOGENOMICS IN DRUG
DESIGN
 The evolution of drug resistance could be reduced by
developing drugs that target the secreted metabolites.
 Identifying the target in the drug discovery process. The
identified target should contain the following…
 It include homology between target and host .
• Discovery of new or improved drugs and vaccines to prevent
multiple resistance of pathogens .
• Antibiotics inhibit essential enzymatic processes and kills the
bacteria .
Contd…
•It include homology between target and host .
•The values of selection criteria can be found easily by querying
publicly available bioinformatics resources, including metabolic pathway
databases such as KEGG (Kyoto encyclopedia of genes and genomes),
protein classification sets such as COGs (clusters of orthologous groups),
and databases of “drug gable” (potentially useful as drug targets)
proteins.
Contd…
CONCLUSION
 It is useful in order to identify specific target genes for the
development of new vaccines and therapeutic approaches .
 Its wide-most application is in Pharmaco-genics .
 It is used to prevent re-emerging infectious diseases from turning
into an epidemic .
 By obtaining the genetic information we can manipulate the gene
expressing the virulence factor to modify the pathogenicity.
 The genetic information should not be misused .
Contd…
REFERENCES
1.Pathogenomics- Genome Analysis of Pathogenic microbes, Wiley-VCH
2.Fungal pathogenomics, Cris Lawrence, Lawrence@vbi.vt.edu
3.Ncbi.nlm.nih.gov/pubmed/
4.Bacterial pathogenomics, www.bcgsc.ca, BC cancer Agency
5.Bacterial pathogenomics, nature insight review, 18 October 2007
6.Fungal pathogenomics, plospathogens.org
7. Drug designing, www.plos1.org
THANK YOU TO ALL THE
DIGNITARIES AND THANK YOU
ONE AND ALL

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patho.ppt

  • 1.
  • 2. Bapuji Institute of Engineering and Technology, DAVANGERE Presented by, Lakshmi kavya Mounika P. V. R. Ranjana Nagendra Jinu D'Souza
  • 3. Contents 1 Introduction 2 Identification of virulence factors 3 Fungal Pathogenomics 4 Bacterial Pathogenomics 5 Pathogenomics in its applied trends 6 Future trends and challenges 7 Pathogenomics in drug design 8 Conclusion 9 References
  • 4. INTRODUCTION  Pathogenic infections leads to increase in morbidity and mortality rate in human and animal population.  Pathogenomics attempts to utilize genomics and metagenomics data from high through-put technologies.  The prevention and treatment of infectious diseases has posed a medical challenge to the researchers. Contd...
  • 5. • Pathogenomics applies the newly gained knowledge to treat and prevent disease. • With the Functional Genomics, we can reveal the pathogenesis-related genes. •The research promotes the development of drugs, diagnostic tools and vaccines . •Comparative Genomics has gained more applicability with the recent increased amount of sequence information.
  • 6. IDENTIFICATION OF VIRULENCE FACTORS Direct Sequence Annotation Tools for Functional Genomics:  The first is the identification of transcripts and the determination of reading frames using programs such as Genscan and Gene predict.  The next step is to analyse the mRNA including the identification of regulatory elements, using an RNA analyser ,it identifies individual regulatory elements in a RNA sequence using a decision tree and executes sequence and secondary structure searches for various elements.
  • 7. Genome Analysis of pathogens as a basis for Pharmacogenomic strategies: • Current methods allow collection of data on a genomic scale involving the complete genome sequence , an overview of the transcriptomes (by EST) and insight into the proteomes. • The available genome sequences of various pathogens provide a wide range of novel gene targets for drug design which can be identified using microarray analysis. Contd…
  • 8. •Detailed analysis of gene expression by software such as Bioconductor and R allows prediction about activated or repressed genes, gene clusters, groups, and pathways in pathogens. • Analysis of all involved pathogen genes and the interacting host genes, enzymes, and pathways by the application of methods such as Pathway alignment and elementary mode analysis. Fig: Depicting Salmonella’s virulence factors
  • 9. FUNGAL PATHOGENOMICS  It occurs to recognise respond and persevere against the invasive infection .  Many chronic air way diseases such as allergy, asthma and various forms of sinusitis are the result of both deleterious alterations in airway functionality and overzealous innate and adaptive response leading to chronic inflammation . Contd…
  • 10. •Alternaria has been associated with chronic respiratory diseases such as IgE-dependent mold allergy, asthma, chronic sinusitis and other allergic airway diseases. • Novel therapeutic strategies, new diagnostics, drug targets and medicine are being developed to reduce the impact of ubiquitous fungi on the plant earth. •In 2004, the NSF-VSDA Interagency Microbial Genome Sequencing Program founded the project entitle. “The genome sequence of the model mesotropic fungus, Alternaria brassicicola”. Contd…
  • 11. •A project team was assembled at the Virginia Bioinformatics Institute[VBI] who played a major role in human genome project. •This team had worked on whole genome shot gun sequencing, BAC library construction Express Sequence Tag[EST] sequencing, database development, genome annotation, and unique transcript profiling technologies. Fig: Alternaria spore
  • 12. BACTERIAL PATHOGENOMICS  The horizontal gene transfer and genome decay .  In Genome dynamics, three main forces have been found to shape genomic evolution, gene gain, gene loss and gene change.  1. Some genetically uniform lineages have emerged recently in evolutionary terms[ex. Bacillus anthracis and Mycobacterium leprae].  2.The recombination can occur between closely related sequences in closely relating strains [ex. Neisseria mehingitedis , hemophylus influenza]. Contd…
  • 13. •3. Wide spread horizontal gene transfer .[ex. many enterobacteria and some staphylococci]. •The whole genome sequencing has been used to detect SNPs. •Genome sequencing also conforms that phase variation is a wide spread source of inter specific genotypic and phenotypic variations. • Horizontal gene transfer may be defined as transfer of genes or genome from one cell to another cell of the same generation. Fig: Bacterial genome dynamics
  • 14. Comparative patho-genomics of bacteria causing infectious diseases in fish: •The genome sequencing has uncovered evolutionary stratergies mediated by horizontal gene transfer, insertional sequence elements, mutations and prophage sequence present in fish pathogens. • The genomes of bacteria are made up of circular or linear chromosomes, extra chromosomal linear or circular plasmids .The genes located on the “core” part of the chromosome exhibit a relatively uniform G+C content end a specific codon usage. Contd…
  • 15. •Bacteria Vibrio are mainly pathogenic to marine and brackish water fish. •Vibriosis, one of the major bacterial diseases is mainly caused by pathogenic species such as Vibrio anguillarum and V.ordalii. •The 96F strain has a type3 secretion system[T3SS2],which is absent in the 775 strain . In the 775 strain three transposase genes are present at the T3SS2 chromosomal location, one of which probably originated from the pJM1,indicating that the gene cluster is in activated by a transposition, deletion, or inversion event. •A striking feature of V.ordalii genome is its significant reduction in size[3.4Mb] compare to the V.anguillarum strain775[4.1Mb]. •V.ordalii lacks the ABC transporter genes, the type6 secretion systems and the genes for microbial collagensase.
  • 16. PATHOGENICS IN ITS APPLIED TRENDS  To study life-threatening human pathogens.  The analysis of the gene pools of pathogenic bacteria including antigenic diversity and antigenic variation results in more effective vaccines and vaccine implementation programs.  The metabolism of the pathogen in the host allows the identification of new targets for anti-infectives and therapeutic approaches.  The study of multiple pathogenic and non-pathogenic microbes interacting in the host will improve the management of multiple infections and will allow probiotic and prebiotic interventions.
  • 17. FUTURE TRENDS AND CHALLENGES  Nearly 25% of the annual deaths worldwide are directly related to pathogens multidrug- resistant tuberculosis and HIV/AIDS are on the rise worldwide; and Staphylococcus and Enterococcus strains in Western hospitals are becoming increasingly resistant to antibiotics.  Scientific information could be misused for bioterrorism . Contd…
  • 18. •In vivo expression analyses and new bio-imaging techniques now enable scientists to investigate the role of individual genes during infection in real time. •The World Health Organization (WHO) in 2004, accordingly addressed the need for action plans to counteract potential bioterrorist attacks; indeed there is no such international body till date to investigate the sudden emergence of infectious diseases.
  • 19. PATHOGENOMICS IN DRUG DESIGN  The evolution of drug resistance could be reduced by developing drugs that target the secreted metabolites.  Identifying the target in the drug discovery process. The identified target should contain the following…  It include homology between target and host . • Discovery of new or improved drugs and vaccines to prevent multiple resistance of pathogens . • Antibiotics inhibit essential enzymatic processes and kills the bacteria . Contd…
  • 20. •It include homology between target and host . •The values of selection criteria can be found easily by querying publicly available bioinformatics resources, including metabolic pathway databases such as KEGG (Kyoto encyclopedia of genes and genomes), protein classification sets such as COGs (clusters of orthologous groups), and databases of “drug gable” (potentially useful as drug targets) proteins. Contd…
  • 21. CONCLUSION  It is useful in order to identify specific target genes for the development of new vaccines and therapeutic approaches .  Its wide-most application is in Pharmaco-genics .  It is used to prevent re-emerging infectious diseases from turning into an epidemic .  By obtaining the genetic information we can manipulate the gene expressing the virulence factor to modify the pathogenicity.  The genetic information should not be misused . Contd…
  • 22. REFERENCES 1.Pathogenomics- Genome Analysis of Pathogenic microbes, Wiley-VCH 2.Fungal pathogenomics, Cris Lawrence, Lawrence@vbi.vt.edu 3.Ncbi.nlm.nih.gov/pubmed/ 4.Bacterial pathogenomics, www.bcgsc.ca, BC cancer Agency 5.Bacterial pathogenomics, nature insight review, 18 October 2007 6.Fungal pathogenomics, plospathogens.org 7. Drug designing, www.plos1.org
  • 23. THANK YOU TO ALL THE DIGNITARIES AND THANK YOU ONE AND ALL