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Aynaz Taheri

Horizontally Transferred Genetic Elements and Their Role in Pathogenesis of Bacterial Disease C. Gyles and P. Boerlin

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Outline

*Transfer of foreign DNA

*Mechanisms of transfer of DNA

*Mobile genetic elements (MGE)

*MGEs in the virulence of 4 major pathogens

*Conclusion

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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

DNA transferred by a virus

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3. Transformation

Direct uptake of naked DNA

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MGEs

Elements Mechanism of Transfer

Plasmid Conjugation

Bacteriophage Transduction

Integrative and conjugative elements

(ICE)

Conjugation

Pathogenicity island (PAI)

Transduction, Conjugation,

Transformation

Insertion Sequences , Transposon

Transformation

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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 function

*Intrabacterial movement of DNA

*They may be transferred to other bacteria by transfer of plasmid or chromosomal DNA

Interrupted DNA sequence

Interrupted DNA sequenceTarget site Target site

TransposonTransposon

Cut and pasteCopy and paste

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Plasmid

*Small DNA molecule within a cell that is physically separated from a chromosomal DNA

*Plasmids can perform conjugation

*Plasmids carry such as genes drug resistance, virulence factors, and fitness

*Plasmid 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: botulinum 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 tRNA

*GEIs 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

chromosome

*Mobilization: conjugation

*Transfer large amount of genetic materials

*Common features with transposons, bacteriophages and plasmids:

• Integrative ability of bacteriophages or transposons

• Transfer mechanisms of conjugative plasmids

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Virulence of Four Pathogens

*Roles of horizontally transferred genes in virulence of bacterial pathogens:

• E. coli

• Salmonella

• Pyogenic Sterptococci

• Clostridium 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 genes

*Genome size from 4.6 to 5.6 Mb

*Complexity of gene organization by Insertions, deletions and rearrangement over time.

E. Coli

Nonpathogenic

Pathogenic Encodes more than 1600 proteins that are not found in nonpathogenic

Plasmids, phages and PAIs transferred to nonpathogenic

Enterotoxigenic E. Coli: diarrhea

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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.

*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 pathogens

*Role of MGEs in the virulence and host adaptation

*Streptococcus 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.

*Streptococcus agalactiae: main hosts are cattle and humans

• Important 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

• Phages, ICE and plasmid

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Clostridium perfringens and Necrotic Enteritis*A 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 evolution

*Conduct genome searches for foreign genes that affect adaptation to the animal or human environment

*Recognize likely developments in the years ahead

*Find activities that accelerate the emergence of new virulent pathogens continuously created through LGT

*Reduce the capability for treating the disease they cause