S -Nitrosated alpha-1-acid glycoprotein exhibits antibacterial activity against multidrug-resistant bacteria strains and synergistically enhances the effect of antibiotics

Abstract

Alpha‐1‐acid glycoprotein (AGP) is a major acute‐phase protein. Biosynthesis of AGP increases markedly during inflammation and infection, similar to nitric oxide (NO) biosynthesis. AGP variant A (AGP) contains a reduced cysteine (Cys149). Previously, we reported that S‐nitrosated AGP (SNO‐AGP) synthesized by reaction with a NO donor, possessed very strong broad‐spectrum antimicrobial activity (IC50 = 10−9‐10−6 M). In this study, using a cecal ligation and puncture animal model, we confirmed that AGP can be endogenously S‐nitrosated during infection. Furthermore, we examined the antibacterial property of SNO‐AGP against multidrug‐resistant Klebsiella pneumoniae and Pseudomonas aeruginosa to investigate the involvement of SNO‐AGP in the host defense system. Our results showed that SNO‐AGP could inhibit multidrug efflux pump, AcrAB‐TolC, a major contributor to bacterial multidrug resistance. In addition, SNO‐AGP decreased biofilm formation and ATP level in bacteria, indicating that SNO‐AGP can revert drug resistance. It was also noteworthy that SNO‐AGP showed synergistic effects with the existing antibiotics (oxacillin, imipenem, norfloxacin, erythromycin, and tetracycline). In conclusion, SNO‐AGP participated in the host defense system and has potential as a novel agent for single or combination antimicrobial therapy.

Inhalant Mammal-Derived Lipocalin Allergens and the Innate Immunity

“…Lipocalins are involved in multiple other functions, such as olfaction, gustation and prostaglandin D 2 synthesis ( 19 , 39 , 56 ). Several lipocalin proteins are acute-phase proteins, thus related to inflammation and innate immunity ( 58 , 59 ). Therefore, neutrophil gelatinase-associated lipocalin or alpha-1-acid glycoprotein, for example, may be used as inflammatory biomarkers in medical conditions ( 60 , 61 ).…”

Niosome‐encapsulated tobramycin reduced antibiotic resistance and enhanced antibacterial activity against multidrug‐resistant clinical strains of Pseudomonas aeruginosa

“…Also, pyocyanin, elastase, and proteases are the main virulence factors of P. aeruginosa , which is enhance the pathogenesis of bacteria 14 . Several studies indicated that the essential role of virulence factors in the pathogenesis of P. aeruginosa in animal models 15 . To date, the researchers are studying the design of novel antibacterial agents that suppressed antibiotic resistance and virulence factors 15,16 .…”

“…Several studies indicated that the essential role of virulence factors in the pathogenesis of P. aeruginosa in animal models 15 . To date, the researchers are studying the design of novel antibacterial agents that suppressed antibiotic resistance and virulence factors 15,16 . Hence, the design of safe and effective new antimicrobial agents with a wide range of effects is necessary to prevent and treat infections caused by P. aeruginosa 17 .…”