Sulfated exopolysaccharide from Bacillus altitudinis MTCC13046 accelerates cutaneous wound healing via dermal fibroblast migration: Insights into an in vivo wound re-epithelialization

Abstract

Bacterial exopolysaccharides with (1 → 3) linked β-glucans and β-galactans have been identified as potent candidates for wound healing. In this study, a sulfated exopolysaccharide (BAP-2), characterized by its major repeating units as [→3)-β-GlcAp-(1 → 3)-(2,6-di-O-SO3)-β-Galp-(1→], was isolated from seaweed-associated Bacillus altitudinis MTCC13046. Whole-genome analysis of B. altitudinis MTCC13046 revealed the presence of biosynthetic gene clusters coding for saccharin. BAP-2 demonstrated anti-inflammatory activity by downregulating the expressions of inflammatory cytokines, such as interferon (IFN)-γ (1.77-fold), interleukins (IL-2/1β/6/12), and tumor necrosis factor (TNF)-α (~87 %) along with nitric oxide (~45 %), while upregulating transforming growth factor-β (3.88-fold) in comparison with lipopolysaccharide-induced RAW 264.7 macrophage and human monocytic THP-1 cells. BAP-2 exhibited biocompatibility with dermal fibroblasts, promoting cell adhesion and proliferation by upregulating Ki-67 (fibroblast proliferation marker) (12.66-fold), epidermal growth factor (5.6-fold), and epithelial-cadherin expressions level (~6-fold), after 48 h. Cell cycle progression and cellular interaction studies showed that administration of BAP-2 promotes conversion of human dermal fibroblast cells into the S phase, highlighting its effect on cell proliferation. In vivo experiments demonstrated approximately 98 % wound closure in BAP-2 administered experimental rats along with re-epithelialization of injured tissue. The pharmaceutical characteristics of the (1 → 3)-linked sulfated exopolysaccharide (BAP-2) suggests it could be an effective candidate for the treatment of cutaneous wound