Effect of N-Acetyl-L-cysteine on Activity of Doxycycline against Biofilm-Forming Bacterial Strains

Abstract

Biofilm-forming bacteria are associated with difficult-to-cure bacterial infections in veterinary patients. According to previous studies, N-acetyl-L-cysteine (NAC) showed an inhibitory effect on biofilm formation when it was applied in combination with beta-lactam antibiotics and fluoroquinolones. The lack of information about the effect of NAC on doxycycline activity against biofilm-forming strains was the reason for conducting this study. Staphylococcus aureus (S. aureus) ATCC 25923, Staphylococcus aureus O74, Escherichia coli (E. coli) ATCC 25922 and Pseudomonas aeruginosa (P. aeruginosa) ATCC 27853 were used to evaluate the activity of doxycycline with and without addition of NAC on planktonic bacteria and on biofilm formation. The minimum inhibitory concentrations (MICs) of doxycycline were not affected by NAC for Gram-negative strains and were found to be two times higher for the strains of S. aureus. The minimum biofilm inhibitory concentrations (MBICs) for Gram-negative bacteria (2 μg/mL for E. coli ATCC 25922 and 32 μg/mL for P. aeruginosa ATCC 27853), determined using a standard safranin colorimetric assay, were higher than the MICs (0.5 and 4 μg/mL, respectively). The data suggest that the combinations of doxycycline and NAC could stimulate the growth of planktonic cells of S. aureus and biofilm-forming E. coli ATCC 25922. NAC did not affect the strong inhibitory effect of doxycycline on the biofilm formation by the strains of S. aureus.

Exploring Immune Redox Modulation in Bacterial Infections: Insights into Thioredoxin-Mediated Interactions and Implications for Understanding Host–Pathogen Dynamics

“…NAC works through several pathways: it reduces disulfide bonds in proteins, scavenges reactive oxygen species, and serves as a precursor for glutathione, a critical antioxidant in cellular defense mechanisms. In addition to its antioxidative properties [18], NAC exhibits antibacterial and anti-biofilm activities, effectively inhibiting the growth of pathogens like S. aureus and E. coli [145][146][147][148][149][150][151][152]. It competes with cysteine for uptake into bacterial cells, impairing protein synthesis and metabolic activities [18].…”