Abstract
Staphylococcus aureus, an opportunistic Gram-positive pathogen, is known for causing various infections in humans, primarily by forming biofilms. The biofilm-induced antibiotic resistance has been considered a significant medical threat. Combinatorial therapy has been considered a reliable approach to combat antibiotic resistance by using multiple antimicrobial agents simultaneously, targeting bacteria through different mechanisms of action. To this end, we examined the effects of two molecules, cuminaldehyde (a natural compound) and tobramycin (an antibiotic), individually and in combination, against staphylococcal biofilm. Our experimental observations demonstrated that cuminaldehyde (20 μg/mL) in combination with tobramycin (0.05 μg/mL) exhibited efficient reduction in biofilm formation compared to their individual treatments (p < 0.01). Additionally, the combination showed an additive interaction (fractional inhibitory concentration value 0.66) against S. aureus. Further analysis revealed that the effective combination accelerated the buildup of reactive oxygen species (ROS) and increased the membrane permeability of the bacteria. Our findings also specified that the cuminaldehyde in combination with tobramycin efficiently reduced biofilm-associated pathogenicity factors of S. aureus, including fibrinogen clumping ability, hemolysis property, and staphyloxanthin production. The selected concentrations of tobramycin and cuminaldehyde demonstrated promising activity against the biofilm development of S. aureus on catheter models without exerting antimicrobial effects. In conclusion, the combination of tobramycin and cuminaldehyde presented a successful strategy for combating staphylococcal biofilm-related healthcare threats. This combinatorial approach holds the potential for controlling biofilm-associated infections caused by S. aureus.
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Data Availability
The datasets generated during the current study may be available from the corresponding author on reasonable request.
Code Availability
Software Minitab 19 (trial version) was used for the present study.
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The authors would like to thank The Neotia University for providing the financial assistance through sanctioning minor grant (R&D/2020/F2) in carrying out the shared research activity.
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RR, PP, PC, MM, SD, SC, AM, MD, RKS, SS, and ADG performed the experiments, analyzed the results, and wrote the manuscript. PT conceived the idea, designed the experiments, and analyzed the results.
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Roy, R., Paul, P., Chakraborty, P. et al. Cuminaldehyde and Tobramycin Forestall the Biofilm Threats of Staphylococcus aureus: A Combinatorial Strategy to Evade the Biofilm Challenges. Appl Biochem Biotechnol (2024). https://doi.org/10.1007/s12010-024-04914-6
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DOI: https://doi.org/10.1007/s12010-024-04914-6