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

Abstract

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. 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. 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). 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. 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.