Marine Fungal Cerebroside Flavuside B Protects HaCaT Keratinocytes against Staphylococcus aureus Induced Damage.

Ekaterina A Chingizova,Anton N Yurchenko,Artur R Chingizov,Dmitry L Aminin,Elena V Girich,Evgeny A Pislyagin,Ekaterina A Yurchenko,Valery V Mikhailov,Ekaterina S Menchinskaya,Irina V Guzhova

doi:10.3390/md19100553

Abstract

Cerebrosides are glycosylated sphingolipids, and in mammals they contribute to the pro-/anti-inflammatory properties and innate antimicrobial activity of the skin and mucosal surfaces. Staphylococcus aureus infection can develop, not only from minor scratches of the skin, but this pathogen can also actively promote epithelial breach. The effect of cerebroside flavuside B from marine sediment-derived fungus Penicillium islandicum (Aniva Bay, the Sea of Okhotsk) on viability, apoptosis, total caspase activity, and cell cycle in human epidermal keratinocytes HaCaT line co-cultivated with S. aureus, as well as influence of flavuside B on LPS-treated HaCaT cells were studied. Influence of flavuside B on bacterial growth and biofilm formation of S. aureus and its effect on the enzymatic activity of sortase A was also investigated. It was found S. aureus co-cultivated with keratinocytes induces caspase-depended apoptosis and cell death, arrest cell cycle in the G0/G1 phase, and increases in cellular immune inflammation. Cerebroside flavuside B has demonstrated its antimicrobial and anti-inflammatory properties, substantially eliminating all the negative consequences caused by co-cultivation of keratinocytes with S. aureus or bacterial LPS. The dual action of flavuside B may be highly effective in the treatment of bacterial skin lesions and will be studied in the future in in vivo experiments.

Highlights

Drugs 2021, 19, 553 induces inflammasomes, generally at lytic concentrations and probably as part of the events leading to cell death by apoptosis and/or pyroptosis, but some are observed at sublytic concentrations
We found that flavuside B inhibits Staphylococcus aureus (SA) biofilm formation, as well as the activity of sortase A enzyme
The dual action of flavuside B may be highly effective in the treatment of bacterial skin lesions and will be studied in in vivo experiments in the future

Summary

Introduction

Cytolytic peptides called phenol-soluble modulins at sublytic concentrations. Cytolytic peptides called phenol-soluble modulins have a strong pro-inflammatory and chemotactic effects on neutrophils and keratinocytes have a strong pro-inflammatory and chemotactic effects on neutrophils and keratinocytes at sublytic concentrations. Worldwide incidence of bacterial skin diseases in 2019 was reat sublytic concentrations. Worldwide incidence of bacterial skin diseases in 2019 was ported by Global Burden Project as 14,684.3 cases per 100,000 of population [3]. It was reported by Global Burden Project as 14,684.3 cases per 100,000 of population [3]. In 2017, an estimated 48.9 million incident cases of sepsis were recorded wide and 11.0 million sepsis-related deaths were reported, representing 19.7% of all global worldwide and 11.0 million sepsis-related deaths were reported, representing 19.7% of all deaths [4] and SA is one of the main cause of this

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