A Wall Fragment of Cutibacterium acnes Preserves Junctional Integrity Altered by Staphylococcus aureus in an Ex Vivo Porcine Skin Model

Abstract

(1) Background alteration of the skin microbiota, dysbiosis, causes skin barrier impairment resulting in disease development. Staphylococcus aureus, the main pathogen associated with dysbiosis, secretes several virulence factors, including α-toxin that damages tight junctions and compromises the integrity of the skin barrier. The use of members of the resident microbiota to restore the skin barrier, bacteriotherapy, represents a safe treatment for skin conditions among innovative options. The aim of this study is the evaluation of a wall fragment derived from a patented strain of Cutibacterium acnes DSM28251 (c40) alone and conjugated to a mucopolysaccharide carrier (HAc40) in counteracting S. aureus pathogenic action on two tight junction proteins (Claudin-1 and ZO-1) in an ex vivo porcine skin infection model. Methods: skin biopsies were infected with live S. aureus strains ATCC29213 and DSM20491. Tissue was pre-incubated or co-incubated with c40 and HAc40. (3) Results: c40 and HAc40 prevent and counteract Claudin-1 and Zo-1 damage (4) Conclusions: c40 and the functional ingredient HAc40 represent a potential non-pharmacological treatment of skin diseases associated with cutaneous dysbiosis of S. aureus. These findings offer numerous avenues for new research.

Targeting S. aureus Extracellular Vesicles: A New Putative Strategy to Counteract Their Pathogenic Potential

“…The stratum corneum was damaged in tissues infected with two strains of S. aureus , as demonstrated by the immunohistochemically detected reduction in Claudin-1 and ZO-1 expression signals. On the other hand, administering c40 and HAc40 treatments led to elevated signal levels comparable to those observed in the control group [ 25 ].…”

“…HA was dissolved in distilled water at 0.5 mg/mL. c40 purified bacterial fragments of C. acnes DSM28251 and HAc40 were used at 25 µg/mL and 0.5 mg/mL, respectively [ 25 ]. α-Hemolysin from Staphylococcus aureus was purchased from Sigma-Aldrich (Merck Spa) Milano Italy (cat.…”

“…Stock solutions were prepared as previously described [ 25 ]. BEVs were treated as follows: a known concentration of BEV (20 ng) was brought into contact with HAc40, HA, and c40 (20 mg/mL) at a final concentration of 1:1 ( v / v ) for 2 h at room temperature under agitation at 200 rpm.…”

“…HA was dissolved in distilled water at 0.5 mg/mL. c40 purified bacterial fragments of C. acnes DSM28251 and HAc40 were used at 25 µg/mL and 0.5 mg/mL, respectively [25].…”

“…To this end, we evaluated the efficacy of a wall fragment derived from the patented strain of C. acnes DSM28251 (provided by Aileens Pharma S.r.l., Nova Milanese, MB, Italy). This wall fragment, referred to as c40 (DEPOSIT: 9517149, Aileens Pharma S.r.l., Nova Milanese, MB, Italy), was tested both independently and in combination with a mucopolysaccharide carrier, specifically hyaluronic acid (HAc40) (DEPOSIT: WO2022243558A1, Aileens Pharma S.r.l., Nova Milanese, MB, Italy) [ 25 , 26 , 27 , 28 ], to counteract the pathogenic potential of extracellular vesicles (EVs) produced by S. aureus ATCC 14458.…”