Last Updated on August 21, 2020 by Sagar Aryal
Toxin manufacturing is the potential of microorganisms known as toxigenesis. It is used by microbes especially by bacteria to induce disease. Bacterial toxins have two types on the basis of their chemical composition called endotoxin, exotoxin. Endotoxin are part of Gram-negative bacteria cell wall and exotoxin are secreted out of a cell by diffusion. These toxins act as weapons for bacteria to attack host cells. The attacking mode varies from enzymatic activity, damaging host cells, immune cell suppression. These actions change the cell response system and ultimately cause cell death.
Endotoxin is a part of the cell wall of gram-negative bacteria. The term endotoxin shows its association with the cell wall. At the molecular level, it is called lipopolysaccharide (LPS) which is a combination of lipids and complex sugar molecules. These lipoglycans structured as lipid layer, core molecule, and polysaccharides make O-antigen. O-antigen is exposed outside and linked by a core molecule to the lipid layer. At the molecular level lipid layer made of highly acylated di-GlcNAc, core consist of oligosaccharides and O-antigen consisted of repeating polysaccharides. The diversity of LPS structure within genera to species and even in some condition LPS varies with different strains of bacteria. These variations also impact on virulence of the organism.
LPS importance for outer membrane
The outer membrane of Gram-negative bacteria composed of majorly by LPS which provides strength to bacterial cells and guard them against chemical agents. LPS is an essential requirement for some Gram-negative bacteria and in a few cases, its removal or mutation does not affect bacteria such as N.meningitids, A.bauminnii, etc. This outer membrane is a defensive blockade to large molecules and hydrophobic compounds of the atmosphere. It is a pervasiveness barrier and if it is removed or mutated organism survival is at risk. It also not allow the action of lysozyme and many antimicrobial products. And they are adhesive agents for colonization.
LPS is a strong trigger of immune reactions among eukaryotes from insects to humans. “LPS lipid A” content is the principal trigger of the immune response. The minimal dose of these components may induce a slight reaction with no symptom or antigen concentration considered mild with which body combats and eliminate them while in case of high amount intake of LPS may become pathological and leads towards fatality. O-antigen of LPS is an immunogenic component and Lipid A has toxic activity. Completely LPS induces inflammatory reactions as well as triggers the complement system by an alternative pathway. Immunogenicity also changes with LPS structural variations. The pyrogenic activity also stimulates by LPS if it introduces in the living organisms.
Exotoxins are discharged from bacterial cells and known as the most poisonous substance able to cause disease. These are heat-sensitive proteins. Gram-positive and Gram-negative bacteria both have the ability to produce exotoxin. The exotoxin production is diversified in a few strains of bacterial species while mostly it is the same in all. In a few species, toxin production is associated with the lysogenic phase. There is a diverse range of exotoxin which are classified according to their site of action namely they are cytotoxin, a neurotoxin, enterotoxin, leukotoxin.
Types of exotoxin
Cytotoxin produced by bacteria to resist killing mechanisms. Many clostridial species make cytotoxin known as large clostridial toxins to cause infection. They disrupt the actin cytoskeleton of cells and alters cell morphology also. Their prime target are regulatory enzymes Rho-GTPase and slightly Ras-GTPase for cytoskeleton structure maintenance. These regulatory molecules also involved in controlling transcription, apoptosis, and alteration. These toxins are made by clostridial species specifically C.difficle, C.novyi, C.perfringens, and C.sordellii.
Toxins damaging neurons are known as neurotoxins. The impact on both established and maturing neurons. Ion concentrations regulation across the cell membrane is lost due to neurotoxin activity. Neurotoxin also affects peripheral nervous system signaling and causes myopathy, neuropathy. These toxins can cause the systemic arrest of the nervous system. Neurotoxin producing species have a wide range such as C.botulinum, C.difficle, C.tetani, and C.barattii, etc.
An exotoxin secreted by Corynebacterium diphtheria is a disease-causing agent of diphtherial infection. This toxic gene is programmed on the prophage of Corynebacterium diphtheria. This toxin stops protein synthesis after entrance into the host cell. Structurally this toxin has three functional domains: surface binding, incorporation into cells, and prevents protein synthesis. This toxin production is an example of lysogeny. This toxin consists of a single polypeptide chain with two disulfide bonds consisted of two fragments A and B. This toxin has unusual potential of infection and the myocarditis establishment is related to this toxin and cell necrosis leads toward death.
These toxins have the ability to amend the transport mechanism of salt and water of trans-membranous enterocytes and they cause no impairment to mucosal tissues. They cause loss of electrolytes due to change in membrane permeability. They commonly causative agents of traveler’s diarrhea and food poisoning. These toxins produce various pathogenic species such as Bacillus cereus, Staphylococcus aureus, Streptococcus pyogenes, and Enterotoxigenic E. coli, etc.
Tetrodotoxin is a non-protein sodium transporter inhibitory toxin. It is a neurotoxin isolated from marine species. It may cause paralysis of the central nervous system as well as the peripheral nervous system. A low dose of tetrodotoxin causes itchiness, the lethargic reaction on fingers, toes mouth, and in case of high dose motion sickness vomiting, respiratory difficulty, paralysis, and death may occur. This toxin is isolated from pufferfishes produced by different bacterial species. Vibrio species produce this toxin specifically.
Bacterial toxin are preparatory molecules for host colonization act as virulence factors. And stimulate the damaging process. There is a toxin variety for infection and function in numerous ways. Immune responsive cells T-cells and antigen-presenting cells are prime targets and their impairment causes disease. This infectious agent elimination is dependent on innate immune response and especially neutrophils and macrophages activity. For complete removal, complement system activated and cell-mediated immunity also active to eliminate infectious agents.