Drug repurposing enhances antibiotic activity in multidrug-resistant staphylococcus aureus through modulation of oxidative stress homeostasis
Year: 2026
Type: article
Abstract: Introduction Antimicrobial resistance represents a major therapeutic challenge, particularly in Staphylococcus aureus , and highlights the urgent need for alternative strategies to enhance the efficacy of existing antibiotics. Modulating bacterial stress-response pathways, especially the RecA-mediated SOS response, may provide a promising adjuvant approach to increase bacterial susceptibility to antibiotic-induced stress. Methods This study investigated the potential of repurposed FDA-approved drugs to act as antibiotic adjuvants following in silico identification of compounds predicted to interact with the bacterial recombinase RecA. An integrated workflow was applied, combining in silico screening, formulation selection and optimization, biochemical validation, and in vitro antibacterial assays. The selected formulation was evaluated alone and in combination with streptomycin using IC 50 determination, oxidative stress assessment, RecA-associated ATPase activity measurement, growth curve, and colony-forming unit enumeration. Results Among the tested formulations, the selected combination enhanced streptomycin activity against resistant S. aureus , leading to a 2.2-fold reduction in IC 50 while showing no marked antibacterial effect when used alone. These findings support its role as an antibiotic adjuvant rather than as a directly active antibacterial treatment. Mechanistic investigation suggested that the potentiation of streptomycin activity was associated with increased oxidative stress and reduced RecA-associated ATPase activity. The improved antibacterial performance of the combination treatment was further confirmed by growth kinetics analysis and colony-forming unit enumeration. Conclusion These findings suggest that targeting RecA can increase bacterial susceptibility to antibiotic-induced stress and enhance streptomycin efficacy against resistant S. aureus . This study supports the development of stress-response-targeted antibiotic adjuvant strategies as a promising approach to improve the therapeutic performance of existing antibiotics.
Source: Frontiers in Pharmacology
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7222939416