The effect of mesenchymal stem cell conditioned medium incorporated within chitosan nanostructure in clearance of common gastroenteritis bacteria in-vitro and in-vivo.

Gastroenteritis infection is a major public health concern worldwide, especially in developing countries due to the high annual mortality rate. The antimicrobial and antibiofilm activity of human mesenchymal stem cell-derived conditioned medium (hMSCsCM) encapsulated in chitosan nanoparticles (ChNPs) was studied in vitro and in vivo against common gastroenteritis bacteria. The synthesized ChNPs were characterized using Zeta potential, scanning electron microscopy (SEM), and dynamic light scattering (DLS) techniques. HMSC-derived conditioned medium incorporated into chitosan NPs (hMSCsCM-ChNPs) composite was fabricated by chitosan nanoparticles loaded with BM-MSCs (positive for CD73 and CD44 markers). The antimicrobial and antibiofilm activity of composite was investigated against four common gastroenteritis bacteria (Campylobacter jejuni ATCC29428, Salmonella enteritidis ATCC13076, Shigella dysenteriae PTCC1188, and E. coli ATCC25922) in-vitro and in-vivo. Majority of ChNPs (96%) had an average particle size of 329 nm with zeta potential 7.08 mV. The SEM images confirmed the synthesis of spherical shape for ChNPs and a near-spherical shape for hMSCsCM-ChNPs. Entrapment efficiency of hMSCsCM-ChNPs was 75%. Kinetic profiling revealed that the release rate of mesenchymal stem cells was reduced following the pH reduction. The antibacterial activity of hMSCsCM-ChNPs was significantly greater than that of hMSCsCM and ChNPs at dilutions of 1:2 to 1:8 (P < 0.05) against four common gastroenteritis bacteria. The number of bacteria present decreased more significantly in the group of mice treated with the hMSCsCM-ChNPs composite than in the groups treated with hMSCsCM and ChNPs. The antibacterial activity of hMSCsCM against common gastroenteritis bacteria in an in vivo assay decreased from > 106 CFU/ml to approximately (102 to 10) after 72 h. Both in vitro and in vivo assays demonstrated the antimicrobial and antibiofilm activities of ChNPs at a concentration of 0.1% and hMSCsCM at a concentration of 1000 µg/ml to be inferior to that of hMSCsCM-ChNPs (1000 µg/ml + 0.1%) composite. These results indicated the existence of a synergistic effect between ChNPs and hMSCsCM. The designed composite exhibited notable antibiofilm and antibacterial activities, demonstrating optimal release in simulated intestinal lumen conditions. The utilization of this composite is proposed as a novel treatment approach to combat gastroenteritis bacteria in the context of more challenging infections.

Correlation between biofilm formation and antibiotic resistance in Pseudomonas aeruginosa: a meta-analysis.

Biofilm formation is one of the important resistance mechanisms in Pseudomonas aeruginosa. This study aimed to consider the correlation between biofilm formation and antibiotic resistance in Pseudomonas aeruginosa through a systematic review and meta-analysis. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) strategies. Scientific databases were searched by MeSH terms and keywords such as "Pseudomonas aeruginosa", "biofilm formation", "antibiotic resistance", "prevalence" AND "Iran", to obtain articles published from 1st January 2016 to 30th November 2019. Studies recording biofilm formation and antibiotic resistance in P. aeruginosa recovered from clinical samples of Iranian patients were included. Data analysis was performed using CMA software. The combined biofilm formation rate was reported as 87.6 % (95% CI: 80-92.5). The heterogeneity index among the selected articles was Q2=96.5, I2=85.5, and t=0.26 (p=0.16). The pooled occurrences of strong, moderate and weak biofilms were 47.7% (95% CI: 28.7-67.3), 30.2% (95% CI: 19.4-43.8), and 27.4% (95% CI: 8.8-59.8), respectively. The pooled prevalence of MDR P. aeruginosa strains was as follows: 62.5% (95% CI: 40-77.2). The highest combined rates of antibiotic resistance were against ceftriaxone and tobramycin with the rates of 79.2.9% (95% CI: 54.2-96.2) and 64.4% (95% CI: 36.3-92), respectively. Also, the lowermost antibiotic resistance rates were against colistin and polymyxin B, with the prevalence of 2.1% (95% CI: 0.2-18.1), and 3% (95% CI: 0.5-17.3), respectively. More than half of the studies included in the present review showed a significant correlation between biofilm formation and antibiotic resistance pattern.