Photoprotective sulfated mannogalactan from heterotrophic Bacillus velezensis blocks UV-A mediated matrix metalloproteinase expression and nuclear DNA damage in human dermal fibroblast

Abstract

Prolonged exposure of human dermal fibroblasts (HDF) to ultraviolet (UV) radiation triggers the production of reactive oxygen species by upregulating the expression of matrix metalloproteinases (MMPs), causing type-I collagen degradation and photoaging. A sulfated (1 → 3)/(1 → 4) mannogalactan exopolysaccharide (BVP-2) characterized as [→3)-α-Galp-{(1 → 4)-α-6-O-SO₃-Manp}-(1 → 3)-α-6-O-SO₃-Galp-(1→] was isolated from seaweed-associated heterotrophic bacterium Bacillus velezensis MTCC13097. Whole genome analysis of B. velezensis MTCC13097 (Accession number JAKYLL000000000) revealed saccharine biosynthetic gene clusters for exopolysaccharide production. BVP-2 administered cells showed noteworthy reduction in mitochondrial superoxide (∼85 %, p < 0.05) and ROS production (62 %) than those exhibited by UV-A irradiated HDF cells. Oxidative imbalance in HDF cells (after UV-A exposure) was recovered with BVP-2 treatment by significantly downregulating nitric oxide (NO) production (98.6 μM/mL, 1.9-fold) and DNA damage (⁓67 %) in comparison with UV-A induced cells (191.8 μM/mL and 98.7 %, respectively). UV-irradiated HDF cells showed a ∼30-50 % downregulation in the expression of MMPs (1, 2, and 9) following treatment with BVP-2. Considerable amount of sulfation (18 %) along with (1 → 3)/(1 → 4) glycosidic linkages in BVP-2 could be pivotal factors for down-regulation of the intracellular MMP-1, which was further supported by molecular docking and structure-activity studies. The (1 → 3)/(1 → 4)-linked bacterial exopolysaccharide (BVP-2) might be used as prospective natural lead to attenuate and mitigate UV-A-induced photoaging.