<p>Evaluation of the Antimicrobial and Antibiofilm Effect of Chitosan Nanoparticles as Carrier for Supernatant of Mesenchymal Stem Cells on Multidrug-Resistant <em>Vibrio cholerae</em></p>

Abstract

Aim The aim of the present study was to evaluate the in vitro antimicrobial and antibiofilm activity of chitosan nanoparticles (CS NPs) incorporated with mesenchymal stem cells-derived conditioned media (MSCs CM) on MDR Vibrio cholerae strains. Materials and Methods Chitosan NPs were prepared and characterized by dynamic light scattering (DLS), scanning electron microscope (SEM) and zeta potential measurement. MSCs CM were prepared and entrapped into MSCs CM-CS NPs composite and its release efficiency was measured. Antibacterial efficacy of nano structures was determined by disk diffusion and broth microdilution methods. Antibiofilm activity was assessed by crystal violet assay. Results BM-MSCs were characterized to be negative for CD34 and CD45 markers, positive for CD73 and CD44 markers, and able to differentiate into osteoblast and adipocyte cells. The mean particle size of 96.6% of chitosan NPs was 414.9 nm with a suitable zeta potential and SEM morphology. Entrapment efficiency of MSCs CM-CS NPs was 76.9%. Unstimulated MSCs CM-CS NPs composite as a novel and proficient therapeutic nanostructure against MDR V. cholerae strains showed the synergistic activity of the two components of MSCs CM and CS NPs, leading to greater bacterial killing compared to control groups. MSCs CM more efficiently inhibited biofilm formation, although MSCs CM-CS NPs was also appeared to be effective in inhibiting biofilm formation compared to CS NPs and control group. Conclusion The designed nanodrug composite showed the best release in conditions mimicking the physiological conditions of the intestinal lumen. Given the fact that no overuse or genetic event would cause the emergence of antimicrobial resistance against the MSCs CM-CS NPs nanodrug, it could be considered as a promising alternative for the treatment of MDR V. cholerae infections in clinical settings.

Antimicrobial Properties of Chitosan and Chitosan Derivatives in the Treatment of Enteric Infections

“…Ingestion of pathogens and disruption of normal microbiota cause enteric infections [ 1 , 2 ]. Enteric infections mainly manifest as fairly distinct clinical syndromes, including acute vomiting, acute watery diarrhea, profuse watery diarrhea, invasive or bloody diarrhea (dysentery), persistent diarrhea, and enteric fever [ 3 ].…”

“…Recently, there is a consensus that antibiotics overuse contributed to increased drug resistance and the resulting dysbiosis [ 2 ]. Novel antibiotics are massively produced, but the continuous fear of the resulting antibiotic resistance and dysbiosis elicited researchers to concentrate on the application of nonantibiotic compounds as antimicrobial agents [ 1 ].…”

Mesenchymal Stem Cells as a Cornerstone in a Galaxy of Intercellular Signals: Basis for a New Era of Medicine

“…Recent in vitro and in vivo studies also reported that secreted products found in MSC-conditioned medium have a wide range of anti-microbial activity, including against E. coli and S. aureus [ 76 , 93 ], E. epidemidis [ 93 ], Vibrio cholerae [ 17 , 94 ], P . aeruginosa [ 95 ], Mycobacterium tuberculosis [ 96 ], Acinetobacter baumannii [ 97 ], and several Candida species [ 98 , 99 ], including effects against biofilm formation [ 100 , 101 ].…”

“…In addition, recent studies highlight the interest in improving antimicrobial effect by combining of MSC secretome-derived products with nanoparticles. Thus, for example, research has shown the synergic effect of MSC-conditioned media coupled with chitosan nanoparticles against multidrug-resistant Vibrio cholerae [ 94 ]. On the other hand, MSC can produce a direct antiviral effect by secreting antibacterial peptides and proteins (IDO, IL-17, etc.)…”

The role of bacterial extracellular vesicles in chronic wound infections: Current knowledge and future challenges

“…149,150 Loading of hEVs with a miRNA miR-21 mimic allowed delivery of the miRNA to target cells to improve Wnt/β-catenin controlled migration of keratinocytes in vitro and wound healing in vivo using a diabetic rat model. 151 The secretome of MSC cultures exerts antimicrobial and antibiofilm activity against both Gram-positive and -negative bacterial species, including S. aureus and P. aeruginosa [152][153][154][155] (for a review of MSC antimicrobial peptides see Alcayaga-Miranda et al 94 ). Impregnating wound dressings with a combination of silver nanoparticles and MSC derived hEV increased wound closure, angiogenesis and alpha smooth muscle actin presence in an murine wound model, while also showing in vivo and in vitro activity against P. aeruginosa and broad in vitro antimicrobial activity against E. coli, S. aureus and Candida albicans.…”