Colistin is considered to be an antimicrobial of last-resort for the treatment of multidrug-resistant Gram-negative bacterial infections. The recent global dissemination of mobilized colistin resistance (mcr) genes is an urgent public health threat. An accurate estimate of the global prevalence of mcr genes, their reservoirs and the potential pathways for human transmission are required to implement control and prevention strategies, yet such data are lacking. Publications from four English (PubMed, Scopus, the Cochrane Database of Systematic Reviews and Web of Science) and two Chinese (CNKI and WANFANG) databases published between 18 November 2015 and 30 December 2018 were identified. In this systematic review and meta-analysis, the prevalence of mcr genes in bacteria isolated from humans, animals, the environment and food products were investigated. A total of 974 publications were identified. 202 observational studies were included in the systematic review and 71 in the meta-analysis. mcr genes were reported from 47 countries across six continents and the overall average prevalence was 4.7% (0.1–9.3%). China reported the highest number of mcr-positive strains. Pathogenic Escherichia coli (54%), isolated from animals (52%) and harboring an IncI2 plasmid (34%) were the bacteria with highest prevalence of mcr genes. The estimated prevalence of mcr-1 pathogenic E. coli was higher in food-animals than in humans and food products, which suggests a role for foodborne transmission. This study provides a comprehensive assessment of prevalence of the mcr gene by source, organism, genotype and type of plasmid.
Live attenuated bacteria are of increasing importance in biotechnology and medicine in the emerging field of cancer immunotherapy. Oral DNA vaccination mediated by live attenuated bacteria often suffers from low infection efficiency due to various biological barriers during the infection process. To this end, we herein report, for the first time, a new strategy to engineer cationic nanoparticle-coated bacterial vectors that can efficiently deliver oral DNA vaccine for efficacious cancer immunotherapy. By coating live attenuated bacteria with synthetic nanoparticles self-assembled from cationic polymers and plasmid DNA, the protective nanoparticle coating layer is able to facilitate bacteria to effectively escape phagosomes, significantly enhance the acid tolerance of bacteria in stomach and intestines, and greatly promote dissemination of bacteria into blood circulation after oral administration. Most importantly, oral delivery of DNA vaccines encoding autologous vascular endothelial growth factor receptor 2 (VEGFR2) by this hybrid vector showed remarkable T cell activation and cytokine production. Successful inhibition of tumor growth was also achieved by efficient oral delivery of VEGFR2 with nanoparticle-coated bacterial vectors due to angiogenesis suppression in the tumor vasculature and tumor necrosis. This proof-of-concept work demonstrates that coating live bacterial cells with synthetic nanoparticles represents a promising strategy to engineer efficient and versatile DNA vaccines for the era of immunotherapy.
Salmonella is a major foodborne pathogen which causes widespread contamination and infection worldwide. Salmonella Typhimurium is one of the leading serovars responsible for human and animal salmonellosis, globally. The increasing rate of antibiotic resistance in Salmonella Typhimurium poses a significant global concern, and an improved understanding of the distribution of antibiotic resistance patterns in Salmonella Typhimurium is essential for choosing the suitable antibiotic for the treatment of infections. To evaluate the roles of animal and human in antibiotic resistance dissemination, this study aims to categorize 11,447 S . Typhimurium strains obtained across the food-chain, including food animals, retail meats and humans for 21 years in the United States by analyzing minimum inhibitory concentrations (MICs) values for 27 antibiotics. Random Forest Algorithm and Hierarchical Clustering statistics were used to group the strains according to their minimum inhibitory concentration values. Classification and Regression Tree analysis was used to identify the best classifier for human- and animal-populations’ isolates. We found the persistent population or multi-drug resistant strains of S . Typhimurium across the four time periods (1996∼2000, 2001∼2005, 2006∼2010, 2011∼2016). Importantly, we also detected that there was more diversity in the MIC patterns among S . Typhimurium strains isolated between 2011 and 2016, which suggests significant emergence of diversified multi-drug resistant strains. The most frequently observed (43%) antibiotic resistance patterns found in S . Typhimurium were tetra-resistant pattern ASSuT (ampicillin, streptomycin, sulfonamides, and tetracycline) and the penta-resistant pattern ACSSuT (ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline). Animals (mainly swine and bovine) are the major source for these two frequently found antibiotic resistance patterns. The occurrence of antibiotic resistant strains from humans and chicken is alarming. Strains were mostly susceptible to fluoroquinolones. Together, this study helped in understanding the expansion of dynamics of antibiotic resistance of S . Typhimurium and recommended fluoroquinolones as a possible treatment options against S . Typhimurium infection.
Analysis of the genome sequence of Vibrio parahaemolyticus reveals two IcmF family genes in putative type VI secretion system (vpT6SS) clusters in chromosomes 1 (icmF1) and 2 (icmF2). The icmF1 gene is present in majority of clinical isolates (87.5 %), but has a low fraction (25.0 %) in environmental isolates. However, icmF2 is contained in all strains of both clinical and environmental sources. Deletion of either icmF1 or hcp1 significantly reduced bacterial adhesion to Caco-2 cells or HeLa monolayers. However, the ΔicmF2 and Δhcp2 mutants showed decreased adhesion only to HeLa monolayers. Western blot analysis showed that Hcp2 was present both in the supernatant and pellet samples in the wild-type strain, but only in the pellet of the ΔicmF2 mutant, indicating that Hcp2 is a translocon of T6SS2. Although vpT6SS1 might be functional in cellular adhesion, the putative translocon Hcp1 was not detectable. Quantitative PCR revealed 10-fold and 17-fold less transcripts of hcp1 and icmF1 mRNA than those of hcp2 and icmF2 accordingly. Thus, we postulate that the putative vpT6SS systems contribute to adhesion of V. parahaemolyticus to host cells.
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