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.

BACTERIAL EXOTOXINS:

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

Autotransporters

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

Abbreviations:

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