Author:
Singh Rupneet,Choudhury Chinmayee,Nambiyar Kaniyappan,Sharma Swati,Singh Lakhwinder,Bhatia Alka,Banerjee Dibyajyoti,Das Ashim,Chakraborti Anuradha
Abstract
AbstractGroup A streptococcus (GAS), Streptococcus pyogenes manifests plethora of diseases through its explicit virulence factors. Among these, the recently deciphered MSCRAMMs, Streptococcal collagen-like (Scls) adhesins are most studied proteins in context of their biophysically stable collagenous-sequence (Gly-X-Y) despite the difference from analogous mammalian-collagen. Based on recent evidence on collagen-mimetic Scls, we elucidated biomaterial-potential of the unmodified, recombinant Scl1 (rScl1). Initially, rScl1 trimeric- assembly yielded its stability in silico than the monomeric-unit. Thereby, rScl1 matrix characterization was confirmed in vitro. rScl1 exhibited high A549 and HepG2 cell- viability—rScl1 dose incremented to 20.0 µg/ml at time points up to 24 hr, and on 24 hr stored-dishes—deliberating it non-cytotoxic. Imploring cell-adhesion potential, we observed increased cell-counts tangential to rScl1-gradient. This affirmative prelude on rScl1 as a supporting-matrix cued its synergy to collagen; we discerned it through rScl1-augmented, full-thickness diabetic wound-closure in vivo and as a first, we studied > 18-month rabbit alloxan-models. We have ascertained re-epithelialization with higher type III collagen in absence of inflammation evidenced morphometrically and histologically. Finally, we correlated our observations through atomistic-evaluation of rScl1-α2β1-integrin interaction, surprisingly, with augmented binding-energy compared to collagen. Hence, connoting recombinant-streptococcal collagen as an ‘alternate’; with further characterization, rScl1 can potentiate important revelations conceding homogeneous and safe, bio-available, biomaterial.
Publisher
Cold Spring Harbor Laboratory