Microbial toxin


Microbial toxins are toxins produced by micro-organisms, including bacteria, fungi, protozoa, dinoflagellates, and viruses. Many microbial toxins promote infection and disease by directly damaging host tissues and by disabling the immune system. Endotoxins most commonly refer to the lipopolysaccharide or lipooligosaccharide that are in the outer plasma membrane of Gram-negative bacteria. The botulinum toxin, which is primarily produced by Clostridium botulinum and less frequently by other Clostridium species, is the most toxic substance known in the world. However, microbial toxins also have important uses in medical science and research. Currently, new methods of detecting bacterial toxins are being developed to better isolate and understand these toxins. Potential applications of toxin research include combating microbial virulence, the development of novel anticancer drugs and other medicines, and the use of toxins as tools in neurobiology and cellular biology.

Bacterial

Bacteria toxins which can be classified as either exotoxins or endotoxins. Exotoxins are generated and actively secreted; endotoxins remain part of the bacteria. Usually, an endotoxin is part of the bacterial outer membrane, and it is not released until the bacterium is killed by the immune system. The body's response to an endotoxin can involve severe inflammation. In general, the inflammation process is usually considered beneficial to the infected host, but if the reaction is severe enough, it can lead to sepsis. Exotoxins are typically proteins with enzymatic activity that interfere with host cells triggering the symptoms associated with the disease. Exotoxins are also relatively specific to the bacteria that produce it; for example, diphtheria toxin is only produced by Corynebacterium diphtheriae bacteria and is required for the diphtheria disease. Some bacterial toxins can be used in the treatment of tumors. Endotoxins most commonly refer to the lipopolysaccharide or lipooligosaccharide that are in the outer plasma membrane of Gram-negative bacteria. Not all strains of a bacteria species are virulent; there are some strains of Corynebacterium diphtheriae that do not produce diphtheria toxin and are considered nonvirulent and nontoxigenic. Additional classifications used to describe toxins include enterotoxin, neurotoxin, leukocidin or hemolysin which indicate where in the host's body the toxin targets. Enterotoxins target the intestines, neurotoxins target neurons, leukocidin target leukocytes, and hemolysins target red blood cells. Exotoxin activity can be separated into specific cytotoxic activity or broad cytotoxic activity based on whether the toxin targets specific cell types or various cell types and tissues, respectively. Lethal toxins refers to the group of toxins that are the obvious agents responsible for death associated with the infection.
Toxinosis is pathogenesis caused by the bacterial toxin alone, not necessarily involving bacterial infection. It can be caused by Staphylococcus aureus toxins, for example.

Examples

Clostridial

There are over 200 Clostridium species in the world that live in mundane places such as soil, water, dust, and even our digestive tracts. Some of these species produce harmful toxins such as botulinum toxin and tetanus toxin among others. Most Clostridium species that do have toxins typically have AB toxins with part of the toxin involved in cellular entry and the other element delivering a toxic cargo, that is often an enzyme into the cell. Clostridial toxins are widespread and are common causes of disease in humans and other organisms.
Clostridioides difficile
Toxin A and Toxin B are the two major toxins produced by Clostridioides difficile. Toxin A and toxin B are glucosyltransferases that cause the antibiotic-associated pseudomembranous colitis and severe diarrhea that characterize disease presentation of Clostridioides difficile infections. The binary toxin toxin CDT is also produced by some strains of C. difficile.
''Botulinum''
are the causative agents of the deadly food poisoning disease botulism, and could pose a major biological warfare threat due to their extreme toxicity and ease of production. They also serve as powerful tools to treat an ever expanding list of medical conditions that benefit from its paralytic properties, an example drug with BoNTs as the active ingredient is Botox. TBotulinum neurotoxins are protein neurotoxins that are produced by the bacteria Clostridium. BoNTs are now largely being studied due to their ability to aid in chronic inflammatory diseases such as acne, multiple sclerosis, and for cosmetic purposes.
Tetanus
Clostridium tetani produces tetanus toxin, which leads to a fatal condition known as tetanus in many vertebrates. Tetanus toxin is produced from Clostridium tetani, a spore forming bacteria commonly found in soil, Tetanus is a paralytic disease that commonly affects newborns and non-immunized individuals. Tetanus enters the body of organisms through wounds or skin breaks and can be found in manure, soil, and dust. Tetanus mechanism includes tetanus preventing the transmission of glycine and γ-aminobutyric acid from inhibitory interneurons in the spinal cord, leading to activation of motor neurons causing contraction. It can also cause dysautonomia through a similar process that leads to autonomic dysinhibition. When tetanus toxin enters the body it is taken up by cholinergic nerve endings travel through axons into the spinal cord, the toxin is subsequently released from motor neurons and reuptaken into inhibitory nerve terminals triggering loss of inhibition and exaggerated reflexes in intoxicated individuals. Tetanus intoxication is a vaccine preventable illness.

Perfringolysin O toxin

Clostridium perfringens is an anaerobic, gram-positive bacteria that is often found in the large and small intestines of humans and other animals. Clostridium perfringens has the ability to reproduce quickly producing toxins relating to the cause of diseases. The pore-forming toxin perfringolysin has the ability to cause gangrene in calves with the presence of alpha toxin.

Staphylococcal

Immune evasion proteins from Staphylococcus aureus have a significant conservation of protein structures and a range of activities that are all directed at the two key elements of host immunity, complement and neutrophils. These secreted virulence factors assist the bacterium in surviving immune response mechanisms.
Examples of toxins produced by strains of S. aureus include enterotoxins that cause food-poisoning, exfoliative toxins that cause scalded skin syndrome, and toxic-shock syndrome toxin that underlies toxic shock syndrome. These toxin examples are classified as superantigens.
Multi-drug resistant S. aureus strains also produce alpha toxin, classified as a pore-forming toxin, which can cause abscesses.

Shiga

s, responsible for foodborne illnesses, are a classification of toxins produced by Shiga toxin-producing Escherichia coli and Shigella dysenteriae serotype 1. Stx was first identified in S. dysenteriae and was later found to be produced by certain strains of E. coli. Stxs act through inhibiting protein synthesis of infected cells and can be divided into two antigenically different groups: Stx/Stx1 and Stx2. Stx1 is immunologically equivalent to Stx; however, it received a separate name to indicate that it is produced by STEC and not S. dysenteriae. Stx2 is produced only by STEC and is antigenically different from Stx/Stx1. The term shiga-like toxins was previously used to further distinguish the shiga toxins produced by E. coli, but nowadays, they are collectively referred to as shiga toxins. Within the STEC strains, a subgroup classified as enterohemorrhagic E. coli represent a class of pathogens with more severe virulence factors in addition to the ability to produce Stxs. EHEC infections result in more severe diseases of hemorrhagic colitis and hemolytic uremic syndrome. There are around 200 strains of STEC, and the wide range of diversity and virulence between them can be partly attributed to phage-mediated horizontal transfer of genetic material.

Anthrax toxin

disease in humans results from infection with toxin producing Bacillus anthracis strains that can be inhaled, ingested in contaminated food or drink, or obtained through breaks in the skin like cuts or scrapes. Domestic and wild animals can also be infected via inhalation or ingestion. Depending on the route of entry, disease can present initially as inhalation anthrax, cutaneous anthrax, or gastrointestinal anthrax, but eventually will spread throughout the body, resulting in death, if not treated with antibiotics. Anthrax toxin is composed of three domains: protective antigen, edema factor, and lethal factor. EF is an adenylate cyclase that targets ATP. LF enzyme is a metalloprotease that confers the lethal phenotype associated with anthrax disease. As LF is the agent responsible for the death of infected hosts, it is classified in the group of lethal toxins.

Diphtheria toxin

is produced by virulent Corynebacterium diphtheriae that infect the mucosal membranes of the throat and nasal cavity causing a gray, thickened lining of the throat, sore throat, weakness, mild fever, swollen glands of the neck, and difficulty breathing. Diphtheria toxin is an ADP-ribosyltransferase that inhibits protein synthesis which causes the symptoms associated with the disease. Diphtheria used to be a leading cause of childhood death until the creation of a vaccine. The diphtheria vaccine contains a diphtheria toxoid, antigenically identical yet inactivated and non-toxic. When the toxoid is introduced to the body in a vaccine, an immune response is mounted without sequelae associated with the toxigenicity.