Role of calcium in the eugenol-mediated reduction of tobramycin resistance in Pseudomonas aeruginosa

Background Pseudomonas aeruginosa infections are difficult to treat because the pathogen is resistant against a multitude of antibiotics including tobramycin. Tobramycin resistance is increased by Ca²⁺ induced transcription of efflux transporters [1] but can be abrogated by eugenol [2].

Aim We investigated the influence of eugenol and Ca²⁺ on tobramycin resistance of P. aeruginosa.

Methods Minimum inhibitory concentrations (MIC) of tobramycin and eugenol against resistant P. aeruginosa isolates (including synergistic concentrations) were investigated by checkerboard microdilution.

Results Eugenol reduced tobramycin resistance of P. aeruginosa. The resistance-modification was specifically reversed by calcium.

Conclusion The inhibition of eugenol-mediated resistance modification by Ca²⁺ provides evidence that eugenol disrupts Ca²⁺ homeostasis which is essential for tobramycin efflux, as shown earlier [3]. The role of Ca²⁺ in the resistance-modifying activity of eugenol was further confirmed by complexing with EDTA. Results indicate that calcium plays a critical role in the reduction of P. aeruginosa tobramycin resistance by eugenol.

Publication History

Article published online:
13 June 2022

• References

• 1 Khanam S. et al. Cell Calcium 2017; 61: 32-43
• 2 Ulanowska M. et al. Int J Mol Sci 2021; 22: 3671
• 3 Mao W. et al. Antimicrob Agents Chemother 2001; 45: 2001-2007