Modulation of host virulence by virus

Some bacterial viruses encode factors that modulate the virulence of bacterial host against a third organism. This change in properties of the host can occur at different levels including bacterial adhesion, spread through human tissues, exotoxin production or protection against immune defenses. These virulence factors are mostly expressed from integrated viral genomes and provide strong advantages to the bacterial host that carry them.

Adhesion

- The phage SM1 encode PblA and PblB that promote binding of Streptococcus mitis to human platelets
– The phage lambda lom gene product promotes adhesion to buccal epithelial cells

Survival of intracellular bacteria
– The phage Gifsy-2 encodes a periplasmic copper- and zinc-cofactored superoxyde dismutase protecting the intracellular bacterium from oxydative stress .

Exotoxin
– Phage encoded Shiga toxin (Stx) acts as a bacterial defense against the eukaryotic predator Tetrahymena
– Phage encoded diphteria toxin causes the disease diphtheria in humans by gaining entry into the cytoplasm of cells and inhibiting protein synthesis.

Invasion
Some phages encode invasins that allow the bacteria to penetrate the eukaryotic host tissue layers or cells.
Some of these proteins catalyze the breakdown of tissues in the eukaryotic host. From a confined site of infection, the bacteria can thus spread to other parts of the organism.
– Hyaluronidase for example breaks down hyaluronan, a constituent of the extracellular matrix to increase tissue permeability and allow bacterial spread.
– The complex formed by staphylokinase and plasminogen (PLG) displays a plasmin-like proteolytic activity which lyses fibrin and causes dissolution if fibrin clots. This activity may improve bacterial invasion of host tissues.

- The gifsy-1 phage encodes gipA helps the bacteria to colonize the small intestine and invade the intestinal epithelium

- Other protein like SopE are invasion factors that are injected in the eukaryotic cell to subvert host key signaling pathways for the benefit of the invading bacteria.
The salmonella phage encoded sopE protein promotes uptake of its host in intestinal epithelial cells

Eukaryotic host immune system evasion
Some phage encoded virulence factor allow the bacteria to evade the eukaryotic host immune system. These factors can alter bacterial antigenicity and thus recognition by the host immune system or provide serum resistance.

Phage-encoded virulence factors

Source:Common themes among bacteriophage-encoded virulence factors and diversity among the bacteriophages involved

Virus Host bacteria Virulence factor Gene Type/function
β-phage Corynebacterium diphtheriae Diphtheria toxin tox Exotoxin
Phage C1 Clostridium botulinum Neurotoxin C1 Exotoxin
Phage H-19B, Enterobacteria phage 933W Escherichia coli Shiga toxin 1A, 1B, 2A, 2B stx1AB
stx2AB
Exotoxin
Phage CTXΦ Vibrio cholerae Cholera toxin A, B ctxAB Exotoxin
Phage ΦC3208 Escherichia coli Hemolysin hly2
stx2AB
Exotoxin
Phage ΦCTX Pseudomonas aeruginosa Cytotoxin ctx Exotoxin
Phage N315 Staphylococcus aureus Enterotoxin P sep Exotoxin
Phage Mu50A Staphylococcus aureus Enterotoxin A sea Exotoxin
Phage Φ13 Staphylococcus aureus Enterotoxin A entA Exotoxin
Phage ΦETA Staphylococcus aureus Exfoliative toxin A eta Exotoxin
Phage ΦPVL Staphylococcus aureus Panton-Valentine leukocidin S, F lukS Exotoxin/Invasin
Phage T12 Streptococcus pyogenes Toxin A speA Exotoxin
Phage CS112 Streptococcus pyogenes Toxin C speC Exotoxin
Phage Ε34 Salmonella enterica Glucosylation rfb Antigenicity modulator
Phage P22 Salmonella enterica Glucosylation gtr Antigenicity modulator
Phage sf6 Shigella flexneri O-antigen acetylase oac Antigenicity modulator
Phage SfX Shigella flexneri Glucosyl transferase gtrB Antigenicity modulator
Phage SopEΦ Salmonella typhimurium Type III secretion effector sopE Invasin
Phage Gifsy-2 Salmonella typhimurium Type III secretion effector ssel Invasin
Phage SopEΦ Salmonella typhimurium Type III secretion effector sopE Invasin
Phage Gifsy-1 Salmonella enterica Type III secretion effector gogB Invasin
Phage Sp4 Escherichia coli Superoxyde dismutase sodC Intracellular survival (macrophages)
Phage Gifsy-2 Salmonella typhimurium Superoxyde dismutase sodC Intracellular survival (macrophages)
Phage Fels-1 Salmonella enterica Superoxyde dismutase sodC-III Intracellular survival (macrophages)
Phage Φ13 Salmonella aureus Staphylokinase sak Invasin
Phage H4489A Streptococcus pyogenes Hyaluronidase hylP Invasin
Phage lambda Escherichia coli Outer membrane protein Lom lom Adhesin
Phage lambda Escherichia coli Outer membrane protein Bor bor Resistance factor to serum complement killing
Phage lambda-like Escherichia coli Outer membrane protein eib Resistance factor to serum complement killing
Phage MAV-1 Mycoplasma arthritidis Vir vir Adhesin
Phage SM1 Streptococus mitis Capsid proteins pblA, pblB pbla, pblb Adhesin
Phage VPIΦ Vibrio cholerae TCP pilus tcp Adhesin
Phage Gifsy-1 Salmonella typhimurium GipA gipA Invasin
.

Matching UniProtKB/Swiss-Prot entries

9 entries grouped by protein (browse by keywords)

All proteins are shown (view only 2 complete proteome entries)

Exotoxin type A (Erythrogenic toxin) (SPE A) (Scarlet fever toxin)


SPEA_BPT12Streptococcus pyogenes phage T12 (Bacteriophage T12)

Shiga-like toxin 1 subunit A (SLT-1 A subunit) (SLT-1a) (SLT-Ia) (EC 3.2.2.22) (Verocytotoxin 1 subunit A) (Verotoxin 1 subunit A) (rRNA N-glycosidase 1)

Select_all Deselect_all  
STXA_BP933Enterobacteria phage 933W (Bacteriophage 933W) reference strain

Shiga-like toxin 2 subunit A (SLT-2 A subunit) (SLT-2a) (SLT-IIa) (EC 3.2.2.22) (Verocytotoxin 2 subunit A) (Verotoxin 2 subunit A) (rRNA N-glycosidase 2)

STXA_BPH30Bacteriophage H30
STXA_BPH19Enterobacteria phage H19B (Bacteriophage H19B)
STXA_BP788Shigella phage 7888 (Shigella sonnei bacteriophage 7888)

Shiga toxin subunit A (EC 3.2.2.22)

Shiga-like toxin 1 subunit B (SLT-1 B subunit) (SLT-1b) (SLT-Ib) (Verocytotoxin 1 subunit B) (Verotoxin 1 subunit B)

Select_all Deselect_all  
STXB_BP933Enterobacteria phage 933W (Bacteriophage 933W) reference strain

Shiga-like toxin 2 subunit B (SLT-2 B subunit) (SLT-2b) (SLT-IIb) (Verocytotoxin 2 subunit B) (Verotoxin 2 subunit B)

STXB_BPH30Bacteriophage H30
STXB_BPH19Enterobacteria phage H19B (Bacteriophage H19B)
STXB_BP788Shigella phage 7888 (Shigella sonnei bacteriophage 7888)

Shiga toxin subunit B