Goals of PATHOGENOMICS related research

1
Goals of PATHOGENOMICS related research

• Chief Scientist Office
• Ministry of Health
• Israel

2
(No Transcript)
3
(No Transcript)
4

• BOTTOM-UP

5
Potential future research topics
6
Enteropathogenes

• E. coli enteropathogenic, enterohemorrhagic
  O157
• Structure and function of the EPEC/EHEC Type III
  protein system
• Delivery of toxic effector proteins into
  infected mammal the type III secretion system

I. Rosenshine
7

• Genomic and bioinformatic screens for
  identification of genes in EPEC and EHEC,
  including genes encoding for toxic proteins
• Genomic global regulation ( transcriptom) of
  expression of genetic network encoding for
  virulence
• Formation and function of surface structures
  including type III secretion system

I.Rosenshine
8
(No Transcript)
9
Salmonellosis

• The most important and frequently occuring
  foodborne disease worldwide
• However

S. Yaron
10
Genetic background

• Leads to variety of symptoms caused by the
  pathogenic Salmonella serovars, from
• Typhoid fever-like infections
• To
• Focal enteritis

S. Yaron
11
Genetic background

• Effector proteins translocated directly to the
  target cells
• Questions

S. Yaron
12
Genetic background

• What are the polymorph of the sequence and
• regulation of expression of the effector
• proteins among the salmonella serovars?

S. Yaron
13
Genetic background

• Is there any Correlation between potency of
• S. Enterica strains and expression profile
• of the virulence factors?

S. Yaron
14

• What is the cell biological function of
• each protein in the network of the virulence
• associated effector proteins?

S. Yaron
15

• How do they contribute to qualify a strain
  either towards typhoid fever-like infections,
  focal enteritis, or an epidemic spread?

S. Yaron
16
In addition

• Molecular basis for development of antibiotic
  resistance
• Screening for presence of antibiotic resistance
  genes or mutations among resistant isolates
• Development of micro- array and real-time PCR-
  based diagnostic capabilities for detection of
  antibiotic resistance genes and/or mutations
  conferring antibiotic resistance

S. Yaron
17
(No Transcript)
18
Group A Streptococcus (GAS)

• Life threatening highly invasive disease such as
  toxic shock syndrome (TSS) and necrotizing
  fasciitis (NF)
• Last two decades marked increase in incidence
  worldwide
• High mortality rates 20-60
• Develops resistance to macrolides and
  erythromycin

E. Hanski
19
In the present

• Better understanding why certain serotypes of GAS
  are associated with specific diseases
• It appears that the profile of expressed
  virulence factors is what determines the severity
  of the disease

E. Hanski
20
Interaction between Bacteria and Hosts defense
mechanism

• Profile of expressed genes in the presence and
  absence of the competence stimulating peptide
  SilCR which attenuates the virulence
• In vitro
• In vivo (murine model)

E. Hanski
21
(No Transcript)
22
Legionella pneumophilapathogenesis system

• Type IV secretion complex composed from 25
  Icm/Dot proteins

G. Segal
23
Legionella pneumophilapathogenesis system

• Effector proteins probably more than 30, that
  translocate into host cells via this secretion
  system
• Uncovering the function of these components, by
  using the genomic sequences available for 3 L.
  pneumophila strains, is one of our major research
  goals

G. Segal
24
(No Transcript)
25
Bacillus anthracis

• Selection of novel vaccine candidates and novel
  virulence factors
• proteins are assayed by classical or high
  throughput functional In- silico identified
  putative in-vitro and in-vivo screening and
  evaluation methods

A. Shafferman
26
Yersinia pestis

• Identification of genes involved in its
  pathogenesis by applying a combination of random
  signature tagged mutagenesis technique (STM) with
  genomic analyses

A. Shafferman
27
(No Transcript)
28
Listeria

• Microbial Thiol- Disulfide Redox Metabolism
• Genetic and Biochemical studies of Ribonucleotide
  Reductase ( coenzyme B12 cross regulates
  expression of class Ia and II ribonucleotide
  reductases via riboswitch and cofactor functions)

Y. Aharonowitz, G. Cohen
29
Listeria

• Novel route for synthesis of gutathione in
  bacterial pathogenes A multifunctional fused
  protein (GshF) integrates the two catalytic
  activities
• Development of new selective and essential
  targets for antibiotics, and their use in
  specific drug discovery programs

Y. Aharonowitz, G. Cohen
30
(No Transcript)
31
(No Transcript)
32
Aspergillus

• Important opportunistic group of pathogens in
  immunocompromised patients
• Fungus can spread from initial site of infection
  to lungs and internal organs
• Invasive Aspergillosis
• Often fatal

N. Osherov
33

• High mortality more than 90 if left untreated
  and 50-70 after aggressive treatment

N. Osherov
34
Research projects and goals

• Conidial (spore) germination and adhesion
• Bioinformatic approach to identify and
  characterize novel Aspergillus cell-wall proteins
• The response evoked in the host lung cells during
  infection
• Aspergillus resistance to antifungal drugs and
  novel drug combinations

N. Osherov
35
(No Transcript)