What is the correlation between atopic dermatitis and Staphylococcus aureus?

Staphylococcus aureus

Atopic dermatitis (AD) is one of the most common chronic dermatologic disorder, that causes red dry skin, itching and inflammatory lesions.

It is a multifactorial skin disease characterized by:

● Skin lesions highly colonized by Staphylococcus aureus,
● An impaired epidermal barrier function,
● An immune dysregulation leading to cutaneous inflammation.

Staphylococcus aureus is a part of the commensal flora of the population worldwide and it asymptomatically colonizes the human skin. However, its proliferation can cause infections and is a marker of atopic condition.

In many cases, bacterial colonization by Staphylococcus aureus is encounter on the skin patients with AD. In fact, this pathogen is present on healthy skin in 5 to 30% of cases, but it colonizes the skin in 60 to 100% of AD patients. This leads to exacerbation of AD by stimulating the inflammatory cascade: its proliferation is responsible for the production of virulence factors that enhance immune activation and skin barrier dysfunction.

AD Treatments

Many treatments help to manage atopic dermatitis (AD), by reducing inflammation and pruritus, rebuilding the skin barrier or avoiding secondary infections, especially by Staphylococcus aureus.

● Topical corticosteroids
● Non-steroidal topical immunomodulators
● Oral antihistamines
● Topical emollients
● Antibiotics
● Antiseptics

These treatment help to relieve the symptoms and many cases improve over time. However, they are not always adapted to all type of lesions or patients. In fact, patients usually worry about the side effects that they can induce, and many of them admit being not completely compliant to their treatment because of their fears.

Another major difficulty is the development of antibiotic resistance, that can reduce the efficacy of antibiotics.

Novel microbiome manipulation with topically applied commensals has been investigated to eradicate S. aureus from AD skin such as autologous transplant with coagulase-negative staphylococcus strains, or topical application of lysate from a non-pathogenic gram-negative commensal bacterium Vitreoscilla filiformis.

Bacteriophage Endolysin Therapy

With the growing incidence of antibiotic-resistant strains, it becomes more and more difficult to treat bacterial infections and alternative solutions are needed.

In order to selectively eradicate S. aureus, a strategy is now emerging: a phage-derived endolysin-based therapy.

Endolysins are enzymes used by bacteriophages that allow them to escape from the bacterial cell during the phage lytic cycle, resulting in bacterial lysis and death ("lysis from within").

In the case of the exogenous application of endolysins to Gram-positive pathogens, which do not have a protective outer membrane, rapid and effective "lysis from without" is caused by endolysins, which makes them interesting as potential antimicrobial agents.

Endolysins are promising novel therapeutics for treatment of S. aureus skin infections.

Numerous approaches have been investigated and demonstrate that a recombinant phage endolysin is able to target specifically this bacterium. Plus, by being applied externally and acting on the cell wall, endolysins don't have to enter the bacterial cell: when used therapeutically, they avoid a majority of the possible resistance mechanisms.

For patients who are refractory to conventional first-line therapy, this could be the solution to treat their condition. The efficacy of recombinant endolysin in alleviating AD symptoms, reducing inflammation and achieving resolution of skin have been proven in many clinical studies.

Bibliography

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