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Deciphering the Pathological Role of Staphylococcal ?-Toxin and Panton-Valentine Leukocidin Using a Novel Ex Vivo Human Skin Model.

ABSTRACT: Staphylococcus aureus alpha-toxin and Panton-Valentine leukocidin (PVL) have been reported to play critical roles in different animal models of skin infection. These models, however, do not completely recapitulate the human disease due to the host specificity of these toxins as well as the intrinsic anatomical and immunological differences between animals and humans. Human skin explants represent a valid alternative to animal models for studying skin infections. Herein, we developed a human skin explant wound model to study the pathogenic role of alpha-toxin and PVL; inflammatory responses elicited by these toxins; and the neutralizing ability of antibodies to mitigate skin damage. Different concentrations of alpha-toxin and/PVL were applied to superficial wounds on human skin explants. Treatment with alpha-toxin resulted in high tissue toxicity and loss of skin epithelial integrity. PVL induced a milder but significant toxicity with no loss of skin structural integrity. The combination of both toxins resulted in increased tissue toxicity as compared with the individual toxins alone. Treatment of the skin with these toxins also resulted in a decrease of CD45-positive cells in the epidermis. In addition, both toxins induced the release of pro-inflammatory cytokines and chemokines. Finally, antibodies raised against alpha-toxin were able to mitigate tissue toxicity in a concentration-dependent manner. Results from this study confirm the key role of ?-toxin in staphylococcal infection of the human skin and suggest a possible cooperation of the two toxins in tissue pathology.

SUBMITTER: Olaniyi RO

PROVIDER: S-EPMC5953321 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Deciphering the Pathological Role of Staphylococcal α-Toxin and Panton-Valentine Leukocidin Using a Novel <i>Ex Vivo</i> Human Skin Model.

Olaniyi Reuben Olayinka RO Pancotto Laura L Grimaldi Luca L Bagnoli Fabio F

Frontiers in immunology 20180508

<i>Staphylococcus aureus</i> alpha-toxin and Panton-Valentine leukocidin (PVL) have been reported to play critical roles in different animal models of skin infection. These models, however, do not completely recapitulate the human disease due to the host specificity of these toxins as well as the intrinsic anatomical and immunological differences between animals and humans. Human skin explants represent a valid alternative to animal models for studying skin infections. Herein, we developed a hum ...[more]

PMID: 29867940

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Project description:IntroductionSkin and soft tissue infections (SSTI) caused by Panton-Valentine leukocidin (PVL)-producing strains of Staphylococcus aureus (PVL-SA) are associated with recurrent skin abscesses. Secondary prevention, in conjunction with primary treatment of the infection, focuses on topical decolonization. Topical decolonization is a standard procedure in cases of recurrent PVL-SA skin infections and is recommended in international guidelines. However, this outpatient treatment is often not fully reimbursed by health insurance providers, which may interfere with successful PVL-SA decolonization.AimOur goal was to estimate the cost effectiveness of outpatient decolonization of patients with recurrent PVL-SA skin infections. We calculated the average cost of treatment for PVL-SA per outpatient decolonization procedure as well as per in-hospital stay.MethodsThe study was conducted between 2014 and 2018 at a German tertiary care university hospital. The cohort analyzed was obtained from the hospital's microbiology laboratory database. Data on medical costs, DRG-based diagnoses, and ICD-10 patient data was obtained from the hospital's financial controlling department. We calculated the average cost of treatment for patients admitted for treatment of PVL-SA induced skin infections. The cost of outpatient treatment is based on the German regulations of drug prices for prescription drugs.ResultsWe analyzed a total of n = 466 swabs from n = 411 patients with recurrent skin infections suspected of carrying PVL-SA. PVL-SA was detected in 61.3% of all patients included in the study. Of those isolates, 80.6% were methicillin-susceptible, 19.4% methicillin-resistant. 89.8% of all patients were treated as outpatients. In 73.0% of inpatients colonized with PVL-SA the main diagnosis was SSTI. The median length of stay was 5.5 days for inpatients colonized with PVL-SA whose main diagnosis SSTI; the average cost was €2,283. The estimated costs per decolonization procedure in outpatients ranged from €50-€110, depending on the products used.ConclusionOur data shows that outpatient decolonization offers a highly cost-effective secondary prevention strategy, which may prevent costly inpatient treatments. Therefore, health insurance companies should consider providing coverage of outpatient treatment of recurrent PVL-SA skin and soft tissue infections.

Dataset Information

Deciphering the Pathological Role of Staphylococcal ?-Toxin and Panton-Valentine Leukocidin Using a Novel Ex Vivo Human Skin Model.

Publications

Deciphering the Pathological Role of Staphylococcal α-Toxin and Panton-Valentine Leukocidin Using a Novel <i>Ex Vivo</i> Human Skin Model.

Similar Datasets

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