Bacterial Toxins Associated with Cancer

January 14, 20090 comments

Traditionally bacterial infections are not considered as a cause of cancer. Recently, some bacteria have been linked to cancer by two mechanisms,
Induction of chronic inflammation
Production of carcinogenic bacterial metabolites

Helicobacter pylori toxins are highlighted in carcinogenesis. Chronic infection with other bacteria such as Salmonella typhi, Citrobacter rodentium, Pasteurella multocida, Bacteroids fragilis and some other bacteria facilitate tumor development.
The term ‘cancer microbe’ is available from past 30 years, to indicate oncogenic viruses. But, in the past bacteria was not considered as a cause of cancer because, cancer does not act like an infectious or contagious disease.
Later few scientists found unusual pleomorphic bacteria that had secondarily infected and cause cancerous growth.

Exotoxins are toxic proteins secreted by both gram positive and gram negative bacteria; some of them are function as superantigens.
Classical exotoxins fall into three categories,
Toxins that damage membranes
Toxins that function at the membrane
Toxins that function intracellularly

Toxins are delivered by five types of secretary systems. They are respectively follows,
ABC transporters
Two-step secretion
Contact-Dependent secretion
Conjugal transfer systems
Of these, Type III and Type IV delivery systems are having greater importance in carcinogenesis. That is the effector protein is directly delivered into the cytoplasm of affected cell.
The basic mechanism is, any bacterial product that interferes with signaling, resulting in the disruption of the normal balance of growth, cell division and apoptosis could encourage tumor formation.

Here is the list of bacterial toxins
associated with cancer:

Toxin Bacterium
CagA Helicobacter pylori
VacA Helicobacter pylori
PMT Pasteurella multocida
BFT Bacteroides fragilis
CNF-1 Escherichia coli

Escherichia coli

Campylobacter jejuni

Shigella dysenteriae
CDT Haemophilus ducreyi

Helicobacter hepaticus

Actinobacillus actinomycetemcomitans
CdtB Salmonella typhi
Cif Escherichia coli
MAP Citrobacter rodentium

Toxin Activity Carcinogenic Potential
CagA Binds to SHP2 and c-Met Cell scattering
VacA Vacuolation Inflammation, Apoptosis
PMT Modifies Gq Proliferation
BFT Cleaves E-cadherin Proliferation
CNF-1 Modifies Rho family Inflammation; Inhibit Cell cycle
CDT DNase DNA damage; Inhibit cell cycle
Cif ? Inhibit cell cycle
MAP ? Proliferation

VacA – Vacuolating cytotoxin A
CagA – Cytokine aggregating toxin
PMT – Pasteurella multocida toxin
BFT – Bacteroids fragilis toxin
CDT – Cytolethal Distending Toxin
CNF 1 – Cytotoxic Necrotizing Factor-1
Cif – Cycle inhibiting factor
MAP – Mitochondrial Associated Protein

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