The expression of the fosfomycin (fos) resistant gene in chitosan nanoparticle-treated Proteus mirabilis isolated from urine samples

Abstract

The emergence of multidrug-resistant Proteus mirabilis is a significant threat to public health due to the high morbidity and mortality associated with catheter-associated urinary tract infections. The clinical treatment options for these infections are becoming less effective, emphasizing the need for alternative antibacterial agents. Chitosan nanoparticles (CS-NPs) have demonstrated antimicrobial activity against a wide range of pathogens. Hence, this study aimed to detect fosfomycin resistance gene in P. mirabilis isolates collected from urine samples, also to study the impact of CS-NPs on the fosA gene expression in P. mirabilis using real-time PCR method. In this cross-sectional descriptive study, 60 strains of P. mirabilis were collected from urine samples. Antibiotic susceptibility tests against nine antibiotics were performed using disk diffusion method. Moreover, multiplex PCR test was performed to investigate the presence of fosA, fosB and fosC genes. Afterwards, MIC of CS-NPs against P. mirablis isolates was determined by microbroth dilution method. Real-time PCR was performed to investigate the expression fosA in isolates treated with sub-MIC concentrations of CS-NPs. Our results showed that ciprofloxacin had the lowest rate of resistance at 15 %, while 48.3 % of the isolates were resistant to fosfomycin. The frequency of the fosA, fosB, and fosC genes were 23.3 %, 8.3 %, and 11.7 %, respectively. The MIC of the synthesized nanoparticle was 500 μg/mL, with a sub-MIC concentration of 250 μg/mL. Treatment with the sub-MIC concentration of the nanoparticle resulted in a statistically significant reduction in the expression level of the fosA gene 0.562 (1.78 downregulation compared to control). The study suggests concerning increase in antibiotic resistance among P. mirabilis isolates. CS-NPs demonstrated effective antimicrobial properties, as evidenced by their ability to reduce the expression of the fosfomycin resistance gene. This suggests that CS-NPs may be a promising option for the treatment of infections caused by Proteus. However, further research is needed to fully evaluate their efficacy and safety.