Aynaz Taheri H orizontally - PowerPoint Presentation

Slide1

Aynaz Taheri

Horizontally Transferred Genetic Elements and Their Role in Pathogenesis of Bacterial Disease

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C.

Gyles

and P.

Boerlin

Outline

Transfer of foreign DNAMechanisms of transfer of DNAMobile genetic elements (MGE)MGEs in the virulence of 4 major pathogensConclusion 2

Transfer of DNA

Foreign DNA originated from another organism and inserted to a bacterium. Characteristics: Different G+C percentage Codon usage Regions that are adjacent with the foreign DNA Horizontal or Lateral Gene Transfer (LGT) Mobile

Genetic Element (MGE) Mechanisms of transfer of DNA

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1. Conjugation

Direct cell-to-cell contact

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2. Transduction

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DNA transferred by a virus

3. Transformation

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Direct uptake of naked DNA

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MGEs

7ElementsMechanism of Transfer

Plasmid

Conjugation

Bacteriophage

Transduction

Integrative and conjugative elements (ICE)

Conjugation

Pathogenicity island (PAI)

Transduction, Conjugation, Transformation

Insertion Sequences , Transposon

Transformation

Insertion Sequence (IS)

Small segment of DNA Encode gene for mobilization and insertion.Simplest type of transposable elements found in bacteria.Two characteristics: 700 to 2500 bp, code proteins in transposition

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Transposon

Barbara McClintock’s discovery of these jumping genes earned her a Nobel prize in1983 Transposons carry other genes in addition to transposition functionIntrabacterial movement of DNAThey may be transferred to other bacteria by transfer of plasmid or chromosomal DNA9

Interrupted

DNA sequence

Interrupted

DNA sequence

Target site

Target site

Transposon

Transposon

Cut and paste

Copy and paste

Plasmid

Small DNA molecule within a cell that is physically separated from a chromosomal DNA Plasmids can perform conjugationPlasmids carry such as genes drug resistance, virulence factors, and fitnessPlasmid encoded many bacterial toxins: Bacillus Anthracis: pathogen of anthrax (PXO1)

Yersinia Pestis: pathogen of plague

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Bacteriophage

Bacterial viruses that invade bacterial cells Composed of  proteins  that  encapsulate  a  DNA  or

 RNA  genome Phages replicate within the bacterium following the

injection

of their genome into its

cytoplasm

Bacterial

toxins

in

the genomes of

phages:

Corynebacterium

diphteriae

Botulism:

b

otulinum

toxin

CTX: cholera toxin

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Pathogenicity Island (PAI)

Genomic islands (GEIs) are large segments (10-200 kb) of foreign DNA GEIs are usually flanked by IS and are inserted close to tRNAGEIs that carry virulence genes are called PAIs Mobilization for PAIs: conjugation, transduction and transformation

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Integrative and Conjugative element (ICE)

Mobile genetic elements that reside in the host cell’s chromosomeMobilization: conjugationTransfer large amount of genetic materials Common features with transposons, bacteriophages and plasmids:Integrative ability of bacteriophages or transposonsTransfer mechanisms of conjugative plasmids

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Virulence of Four Pathogens

Roles of horizontally transferred genes in virulence of bacterial pathogens:E. coliSalmonellaPyogenic SterptococciClostridium

perfringens and Necrotic Entries

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E. Coli

Escherichia coli is a rod-shaped bacterium of the  genus  Escherichia.Core of important genes + accessory genome

Core DNA: ratio of G+C 50.8%, 1700 genesGenome size from 4.6 to 5.6 MbComplexity

of gene

organization by

Insertions, deletions and rearrangement

over time.

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E. Coli

Nonpathogenic

P

athogenic

E

ncodes

more than 1600 proteins that are not found in nonpathogenic

Plasmids, phages and PAIs transferred to nonpathogenic

Enterotoxigenic E. Coli: diarrhea

Salmonella

A genus of rod-shaped bacteria of the enterobacteriaceae family.  Salmonella bongori

, Salmonella enterica

A pathogen

that can invade intestinal

cells and causes

different enteric and systemic diseases

.

E. Coli and Salmonella have the same

ancestor.

Accessory genome consisting of PAIs,

bacteriophages, and plasmids

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21 PAIs in Salmonella, called Pathogenicity Islands Salmonella (PIS)

PIS-

1

and

PIS-2

:

Invasion

in

nonphagocytic

cells and

replication

in phagocytic and

nonphagocytic

cells.

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Pyogenic Streptococci

An important group of human and animal pathogensRole of MGEs in the virulence and host adaptationStreptococcus pyogenes: human specific pathogen Local pyogenic infections, septicemia, toxic shock syndrome, necrotizing fasciitis and

postinfection rheumatic fever

113 genes acquired by S.

pyogenes through LGT are located in

prophages

,

including 5 virulence

genes.

S

treptococcus

agalactiae

:

main

hosts

are cattle and humans

I

mportant

LGT between S.

agalactiae

and S.

pyogenes

ICEs

in S.

agalactiae

containing virulence genes

and adaptation genes

in cattle

Streptococcus

canis

,

streptococcus

equi

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Pyogenic Streptococci

Streptococcus canis: was first isolated in dogs An important pathogen of dogs and also other animal species, including cattle Presence of multiple MGEs in S.

canis involving virulence genes

P

hages, ICE and plasmid

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Clostridium perfringens

and Necrotic EnteritisA rod-shaped bacterium of the genus Clostridium. C.Can be found as a normal component of decaying vegetation, marine sediment, the intestinal tract of humans and other vertebrates, insects, and soil. Plasmids have a critical role in diseases: tetanus toxin, enterotoxin

, cytotoxin, NetB toxin

Necrotic

Enterities

: hosted by poultry

Necrotic enteritis has been identified in broilers, laying hens, turkeys and quail

Caused by

toxins

produced by C.

perfringens

MGEs have important role on this economically important disease

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Conclusion

Understanding of bacterial adaptability, pathogenesis, and evolutionConduct genome searches for foreign genes that affect adaptation to the animal or human environmentRecognize likely developments in the years aheadFind activities that accelerate the emergence of new virulent pathogens continuously created through LGT

Reduce the capability for treating the disease they cause

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