Evaluation of Antimicrobial Effects of Photo-sonodynamic Antimicrobial Chemotherapy Based on Nano-micelle Curcumin on Virulence Gene Expression Patterns in Acinetobacter baumannii

Abstract

Background: Abaumannii baumannii rapidly resistant to a wide range of antimicrobial agents. The combination of Antimicrobial Photodynamic Therapy (aPDT) and Sonodynamic Antimicrobial Chemotherapy (SACT), known as Photo-Sonodynamic Antimicrobial Chemotherapy (PSACT), has received considerable attention as one of the emerging and promising strategies against microbial infections.

Objective: This study aimed to investigate the antimicrobial effects of PSACT based on nano-micelle curcumin (N-MCur) on the virulence gene expression patterns in A. baumannii.

Materials and methods: N-MCur as a photo-sonosensitizer was synthesized and confirmed. To determine sub-significant reduction dose of PSACT, sub-significant reduction dose of N-MCur and blue laser light during aPDT, and ultrasound power output during SACT was assessed. Finally, changes in the expression of genes involved in treated A. baumannii by minimum sub-significant reduction dose of PSACT were determined using quantitative real-time-PCR (qRT-PCR).

Results: PSACT using 12.5 mM N-MCur at the ultrasound power outputs of 28.7, 36.9, and 45.2 mW/cm² with 4 min irradiation time of the blue laser, as well as 6.2 mM N-MCur at an ultrasound power output of 45.2 mW/cm² plus 3 min blue laser irradiation time exhibited the significant dosedependent reduction against A. baumannii cell viability compared to the control group (P<0.05). After treatment of A. baumannii using 3.1 mM N-MCur + 2 min blue laser irradiation time + 28.7 mW/cm2 ultrasound as the minimum sub-significant reduction doses of PSACT, mRNA expression was significantly upregulated to 6.0-, 11.2-, and 13.7-folds in recA, blsA, and dnaK and downregulated to 8.6-, 10.1-, and 14.5-folds in csuE, espA, and abaI, respectively.

Conclusion: N-MCur-mediated PSACT could regulate the expression of genes involved in A. baumannii pathogenesis. Therefore, PSACT can be proposed as a promising application to treat infections caused by A. baumannii.

Keywords: Acinetobacter baumannii; antimicrobial photodynamic therapy; biofilms; chemotherapy; curcumin; sonodynamic therapy.