Toxin induced pathogenesis by selected bacterial pathogens

Toxins are one of the important virulence factors of bacterial pathogens. They are produced to induce pathogenesis in various hosts. Two types of toxins exo and endo with chemically different properties are known to be produced by bacteria. Exotoxins are secreted by living cells while as endotoxins are released from denatured or lysed cells of Gram negative bacteria. Exotoxins are proteins and hence heat labile. They are neutralized by antitoxins or can be converted to toxoids. Very small dose of exotoxin is very lethal as compared to endotoxins which are required in large quantity to be effectively potent. Generally, endotoxins are lipopolysaccharides. Examples of exotoxins include: diphtheria, botulinum, tetanus, cholera, streptolysin O and S; Alpha toxin or clostridial toxin of Clostridium perfringens, staph α of Staphylococcus aureus, staphylococcal enterotoxin, Panton-Valentine factor, ST and LT of Escherichia coli, exotoxin A of Pseudomonas aeruginosa, shiga of Shigella dysenteriae, anthrax of Bacillus anthracis, pertussigen of Bordetella pertussis and erythrogen of Streptococcus pyogenes. Based on their mode of actions exotoxins are categorized as neurotoxins, cytotoxins and enterotoxins. On the contrary, all endotoxins are heat stable. They show typical pharmacological effects such as pyrogenicity, blood changes accompanied by fever, internal hemorrhage and symptoms of toxic shock such as decreased blood pressure, rapid pulse, exhaustive breathing, circulatory collapse or unconsciousness. They are released during late growth phase from outer membrane of cell wall of Gram negative bacteria. Potency of both the toxin types is generally expressed as LD50 dose and MLD/LD100: a dose that kills 100% test animals. LD50 is a dose that kills 50% test animals.

Toxins of human pathogenic food poisoning bacteria
Staphylococcal food poisoning (SFP), enteric food poisoning (EFP) and clostridial food poisoning (CFP) are 3 characteristic examples of pathogenesis caused by bacterial toxins. Staphylococcal poisoning is caused by toxin of S. aureus. Severe nausea, vomiting accompanied by diarrohea are some of the symptoms of the poisoning. This exotoxin is called as enterotoxin. Its action is thought to be of cytotoxic acting on intestinal and stomach cell wall and possessing neurotoxic activity which can directly act on central nervous system following the absorption in upper gastrointestinal tract. SFP is caused by ingestion of improperly stored food in which S. aureus has multiplied. After the ingestion of contaminated food, the symptoms of poisoning are evident within 1-7hrs of onset period. Enterotoxin is heat stable even at 1000C. If foods are stored below 40C, toxin is not produced. Toxin has been detected in meat, confectionary and milk products.

Clostridial food poisoning is caused by C. perfringens. Ingestion of large number of live cells in vegetative state alongwith contaminated food is the main cause of food poisoning. Boiling and slow cooling of food under anoxygenic conditions allows spore germination followed by proliferation of vegetative cells. Food storage conditions such as oxygen deprivation allow clostridial spores to germinate. Onset is by 24hrs with the symptoms like diarrohea with severe abdominal pain. Other clostridial neurotoxins like botulinum and tetanus binds to motor neurons and prevents release of neurotransmitter acetylcholine. Tetanus toxin binds to nerve cells and blocks inhibitory impulse transmission.

Enteric food poisoning caused by enteric bacteria like E.coli, Salmonella typhimurium, Vibrio cholera, S. dysenteriae produce enterotoxins which stimulate abdominal pumping of electrolytes and water into colon. It is caused by elevating intracellular cAMP (cyclic adenosine monophosphate) concentration by toxins cholera and LT, cGMP (cyclic guanosine monophosphate) elevation by ST and stops protein synthesis in intestinal mucosal cells by interfering 60S ribosomal unit. Cytotoxins like streptolysin O and Sand diphtheria penetrates host cells and protein elongation factor to stop protein synthesis. O and S toxins destroy integrity of phagocyte cell membrane membrane. Cell lysis followed by intracellular release of hydrolytic enzymes is characteristic feature of EFP toxins.

Toxins of phytopathogenic bacteria
Agrobacterium tumefaciens, Clavibacter michiganense, Erwinia carotovora, Pseudomonas lycopersicum, P. syringae, Rhodococcus fascians and Xanthomonas campestris are all agriculturally important plant pathogenic bacteria in which infection of crop plants is mediated by production of phytotoxins. Phytotoxins are not host specific but they directly act on plant inducing symptoms like chlorosis, necrosis or wilting which eventually leads to development of disease. Most of the phytotoxins are lipopeptides, peptides or β-lactam amphipathic molecules. Their amphipathic nature enables them to interact with host cell wall membrane to the formation of pores. Cell wall porosity increases membrane permeability to cations resulting in cell wall lysis and necrotic symptoms. This has been characteristic functional property of phytotoxins syringomycin, syringopeptin, tabtoxin and phaseolotoxin of Pseudomonas spp. Syringotoxins, phaseolotoxin and coronatines are some of the phytotoxins which are synthesized during cold weather. They are synthesized at cold temperatures of 10-20˚C and hence diseases caused by these phytopathogens are more prevalent in winter season. Phytotoxins produced by Xanthomonas spp. are carboxylic or phenolic acids that generally induce necrotic symptoms during pathogenesis. Phytopathogens also produce plant growth regulators such as auxins, cytokinins, gibberellins, and ethylene in their plant hosts during infection resulting in abnormal growth like galls or tumors and related functions. Phytotoxins are commercially produced as important agrochemicals.

Toxins of entomopathogenic bacteria
Bacteria from Bacillus thuringiensis are very important insect pathogens or entomopathogenic bacteria. Their pathogenic potential has been commercialized as biological insecticide and one of the specific biocontrol measures against insect pest from the class Lepidoptera. B. thuringiensis' toxin thuringin is a protein crystalline parasporal body. When these bacteria are ingested by insect larvae of lepidopterans, toxic crystals are synthesized. Crystals are dissolved in internal body temperature of larvae and cause erosion of gut epithelium. Certain Gram negative bacteria associated with host nematodes in soil have been known to be toxic to different insect species. This bacteria-nematode symbiotic association has also been regarded as one of the natural biocontrol measures by plant pathologists.

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