Synergy between “Probiotic” Carbon Quantum Dots and Ciprofloxacin in Eradicating Infectious Biofilms and Their Biosafety in Mice

Pharmaceutics

卷:13

Guang Yang¹  Linqi Shi¹  Henk J. Busscher²  Henny C. van der Mei²  Yanyan Wu³  Yijin Ren³ 

[1] State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China;

[2] University of Groningen and University Medical Center Groningen, Department of Biomedical Engineering, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands;

[3] University of Groningen and University Medical Center of Groningen, Department of Orthodontics, Hanzeplein 1, 9700 RB Groningen, The Netherlands;

关键词: matrix disruption;    antibiotics;    Bifidobacterium breve;    Escherichia coli;    reactive oxygen species;    intestinal infections;   

DOI  :  10.3390/pharmaceutics13111809

来源: DOAJ

【 摘 要 】

Orally administrated probiotic bacteria can aid antibiotic treatment of intestinal infections, but their arrival at their intestinal target site is hampered by killing in the gastrointestinal tract and by antibiotics solely intended for pathogen killing. Carbon-quantum-dots are extremely small nanoparticles and can be derived from different sources, including bacteria. Here, we hypothesize that carbon-quantum-dots inherit antibacterial activity from probiotic source bacteria to fulfill a similar role as live probiotics in intestinal infection therapy. Physico-chemical analyses indicated that carbon-quantum-dots, hydrothermally derived from Bifidobacterium breve (B-C-dots), inherited proteins and polysaccharides from their source-bacteria. B-C-dots disrupted biofilm matrices of Escherichia coli and Salmonella typhimurium biofilms through extensive reactive-oxygen-species (ROS)-generation, causing a decrease in volumetric bacterial-density in biofilms. Decreased bacterial densities leave more open space in biofilms and have enhanced ciprofloxacin penetration and killing potential in an E. coli biofilm pre-exposed to probiotic B-C-dots. Pathogenic carbon-quantum-dots hydrothermally derived from E. coli (E-C-dots) did not disrupt pathogenic biofilms nor enhance E. coli killing potential by ciprofloxacin. B-C-dots were biosafe in mice upon daily administration, while E-C-dots demonstrated a decrease in white blood cell and platelet counts and an increase in C-reactive protein levels. Therefore, the way is paved for employing probiotic carbon-quantum-dots instead of viable, probiotic bacteria for synergistic use with existing antibiotics in treating intestinal infections.

【 授权许可】

Unknown