EXHC FROM MAMMALIICOCCUS SCIURI: METABOLIC OUTCOMES OF INDUCED CELLULAR NECROSIS

Exfoliative toxins (ETs) are glutamyl endopeptidases (GEPs), members of the serine protease family similar to chymotrypsin (CLSPs), and are essential in the development of various dermatological pathologies. Exfoliative toxin C (ExhC), secreted by Mammaliicoccus sciuri, is a CLSP that has been identified as a reserve protein due to its necrotizing action on various cell lines, its role in inhibiting macrophage phagocytosis and causing skin exfoliation in mice and pigs. This latter function is attributed to the high affinity of ExhC for desmoglein-1 (in mice and pigs), a cadherin that aids in cell adhesion in the epidermis. Although the amino acid residues responsible for ExhC-induced necrosis have been identified, the specific cellular metabolic pathways leading to cell death are not yet fully understood. In this study, we employed nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques to investigate the metabolic pathways impacted by ExhC's necrotic activity in the BHK-21 cell line. Cells exposed to sub-toxic doses of ExhC exhibited notable changes in their metabolic profile, primarily affecting pathways related to oxidative stress protection, energy production, and gene expression. The data point to possible ways in which ExhC carries out its function and point out that this toxin can cause cellular injury, even when its concentration is low.

This work is supported by FAPESP (2020/08615-8) and CNPq (309940/2019-2 and 316398/2021-7).