Biomedical and Biotechnology Research Journal (Jan 2024)
Unveiling the antimicrobial potential of 7-o-succinyl macrolactin F from Bacillus subtilis Group against HtsA siderophore receptor of Staphylococcus aureus: A Computational exploration
Abstract
Background: Staphylococcus aureus remains a prominent pathogen within health-care environments due to its extensive repertoire of virulence factors. The escalating prevalence of antibiotic-resistant strains has underscored the urgency of identifying alternative treatment strategies. The study focuses on the HtsA siderophore receptor, an integral cell wall component of all S. aureus strains, responsible for iron acquisition from the host environment. Here, we investigate the potential of Bacillus sp. derived macrolides as inhibitors of this critical iron uptake mechanism. Methods: Sixteen distinct macrolide ligands were evaluated for their ability to disrupt iron acquisition by S. aureus through interaction with the HtsA receptor. Employing molecular docking and subsequent molecular dynamics (MDs) simulations, the binding interactions and dynamic behaviors of these ligands with the receptor were assessed. Results: Notably, the complex formed between 7-O-succinyl macrolactin F and HtsA demonstrated a good binding affinity of − 8.5 kcal/mol, outperforming the binding affinity of staphyloferrin A, which exhibited a binding affinity of − 6.9 kcal/mol. MD simulations further corroborated the stability of the 7-O-succinyl macrolactin F-HtsA complex over time, suggesting the potential for this interaction to be harnessed as a novel therapeutic strategy not only for existing antibiotic-resistant strains but also for those that may arise in the future. Conclusion: The findings propose Bacillus species-derived macrolides as potential adjuvant therapies for S. aureus infections, pending comprehensive safety assessments. This research lays the foundation for the development of innovative antimicrobial agents targeting essential virulence-associated mechanisms in S. aureus.
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