Introduction
The hazardous human pathogen Staphylococcus aureus brings on several disorders. Staphylococci secrete a broad spectrum of diverse proteins that make the bacterium virulent (highly severe in its effect), in contrast to many bacteria whose virulence primarily depends on producing a single or small number of virulence factors. These elements are necessary for staphylococcal virulence as a whole. However, they mostly lack the traits of everyday toxins. They do not operate independently to cause specific symptoms when purified and provided without the bacterium. When only one component is eliminated, bacterial pathogenicity is not decreased. S. aureus infection symptoms are brought on by common toxins such as toxic shock syndrome toxin 1 (TSST-1), enterotoxins, and exfoliative toxins (ETs).
Which Syndromes Are Caused Due to Exfoliative Toxins?
The syndrome commonly caused due to exfoliative toxins is listed below:
Staphylococcal Scalded Skin Syndrome (SSSS): It is also known as Ritter's illness,and skin exfoliation is its primary feature. Fever, malaise, lethargy, and poor feeding are early SSSS symptoms. An erythematous rash and large, fragile, fluid-filled blisters develop after these symptoms. When the blisters rupture mechanically, the injured body parts lose their protective epidermal layer. The mucosa is unaffected; only the skin is implicated. Large areas of the body are affected by SSSS, and the lesions are frequently sterile. Bullous impetigo is the term used to describe a localized form of SSSS that is limited to the infection sites. The only etiological difference between the two disorders is the degree of skin damage.
Along with antibiotic therapy, keeping the body at a constant temperature and covering any exposed skin to prevent secondary infections and fluid loss is advised. While the immune system and renal impairment are found to be susceptibility factors in adults, neonates, and babies are the primary populations affected by SSSS. Children who have received treatment have a low mortality rate of under five percent. Adult fatality rates are significantly higher, reaching 59 % in certain studies. The fact that SSSS frequently co-occurs with severe underlying disease explains why adult mortality is more elevated. Adults with isolated episodes of SSSS who had no apparent underlying condition have also been documented.
How Are the Toxins Identified?
Baron Gottfried Ritter von Rittershain originally outlined the characteristics of SSSS in 1878. Lyell discovered the connection between skin exfoliation and S. aureus in 1967. Because the toxin is transported from far-off sites of infection through the bloodstream, the blister fluid and exfoliated regions are frequently free of cultivable staphylococci, resulting in this substantial delay. Lyell hypothesized the presence of a hypothetical toxin in 1972 and established the production of blistering with sterile filtrates of bacterial cultures.
Early animal investigations demonstrated that S. aureus strains isolated from patients with SSSS could cause blistering in mice. Later, it was proven that bacteria is not required because model animals can develop blisters when exposed to a soluble component found in the sterile filtrates of bacterial cultures. These early investigations verified that the apparent illness signs are all purely the result of a soluble toxin. Infusing newborn mice with toxin-producing strains or giving them sterile culture filtrates recreated the symptoms of human SSSS, creating a viable animal model. After being refined, the toxin was discovered to be a protein of about 30 kD. It was soon shown that there are at least two serotypes of ETs.
What Are the Targets of Exfoliative Toxins in the Skin?
By the middle of the 1990s, it was widely believed that ETs would turn out to be proteases whose activity is only displayed under specific, unknown conditions. While mitogenic activity, whether physiologically relevant or just seen under specific experimental conditions, was undoubtedly not directly related to the core symptoms of SSSS, their proteolytic activity appeared to be directly responsible for skin exfoliation. The target molecule, whose hydrolysis would cause skin exfoliation, was the only missing piece of the puzzle.
Only the outermost layers of skin, not the mucosa or deeper skin layers, are affected by blistering in SSSS. The selectivity of desmoglein cleavage and the varied expression of specific desmogleins in various layers of the skin and mucosa provide a magnificent explanation for this phenomenon. The ETs preferentially hydrolyze dsg-1 (desmogleins), whereas Dsg-3 is unaffected. All layers of the skin exhibit Dsg-1, whereas only the deeper layers express Dsg-3. Exfoliation only happens in the stratum granulosum, where Dsg-3 is absent since Dsg-3 compensates for the disruption of Dsg-1 by ETs in the deep layers of the skin.
What Is the Susceptibility of Exfoliative Toxins?
SSSS particularly impacts neonatal in humans. The same effects are seen in mouse models, where the animals are only vulnerable until day seven of life. Two paths in the search for a reasonable explanation were deduced from the known susceptibility factors in adults. First, it is well known that immune system impairments, such as AIDS (acquired immune deficiency syndrome), chemotherapy for lymphoma, and pharmaceutical immunosuppression in autoimmune illnesses, are risk factors for SSSS and bullous impetigo in adult human subjects. Second, cross-reactive antibodies were proposed as the mechanism for toxin neutralization. Studies on adult mice showed that immunosuppressant therapy made them more vulnerable to S. aureus strains that produce ETs.
Additionally, no rise in susceptibility to a purified toxin was noted. Studies on mice showed that humoral response was not a factor in toxin tolerance. In this animal model, there was no difference in the rate at which toxin resistance developed or the degree of resistance in adulthood. In light of the immune system's involvement, the details of the process of resistance between people and mice may vary. SSSS in adults is also susceptible to severe kidney damage. There is evidence that the rate at which poison is cleared from the bloodstream determines how susceptible mice are to it and that the immune system's overall health has no impact. In the first week after birth, toxin clearance rises sharply along with the emergence of resistance. As was already indicated, the general health of the immune system is also significant in humans as opposed to mice. Deregulation of immunological responses brought on by renal impairment may make a person more vulnerable to pathogen infection or the toxin itself.
Conclusion
The staphylococcal scalded skin syndrome, a blistering skin condition that is more common in newborns and young children as well as adults with underlying diseases, is brought on by the exfoliative toxins of Staphylococcus aureus.
