Abstract
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.
Highlights
The ongoing increase in the number of antimicrobial-resistant bacterial strains has made the treatment of infectious biofilms across the human body extremely difficult, and in many cases, antibiotics have lost a considerable part of their usefulness [1,2,3]
carbon quantum dots (C-dots) derived from probiotic B. breve (B-C-dots) and pathogenic E. coli (E-C-dots) sources both possessed spherical shapes (Figure 1a) with average diameters of 8.0 ± 1.3 and 7.5 ± 1.4 nm, respectively (Figure 1b)
Comparisons included spectroscopies on the freeze-dried bacteria employed for carbonization
Summary
The ongoing increase in the number of antimicrobial-resistant bacterial strains has made the treatment of infectious biofilms across the human body extremely difficult, and in many cases, antibiotics have lost a considerable part of their usefulness [1,2,3]. Probiotic bacteria are predominantly administered orally to assist the development of Pharmaceutics 2021, 13, 1809. A combination of probiotic bacteria with existing antibiotics has been demonstrated to synergistically increase antibiotic efficacy against infectious biofilms [11]. In the clinical scenario, this synergy is difficult to exploit because probiotic bacteria may be killed by acidic gastric fluid and by the antibiotics with which they are co-administered
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