Project description:<p>The study of antimicrobial resistance (AMR) in infectious diarrhea has generally been limited to cultivation, antimicrobial susceptibility testing and targeted PCR assays. When individual strains of significance are identified, whole genome shotgun (WGS) sequencing of important clones and clades is performed. Genes that encode resistance to antibiotics have been detected in environmental, insect, human and animal metagenomes and are known as "resistomes". While metagenomic datasets have been mined to characterize the healthy human gut resistome in the Human Microbiome Project and MetaHIT and in a Yanomani Amerindian cohort, directed metagenomic sequencing has not been used to examine the epidemiology of AMR. Especially in developing countries where sanitation is poor, diarrhea and enteric pathogens likely serve to disseminate antibiotic resistance elements of clinical significance. Unregulated use of antibiotics further exacerbates the problem by selection for acquisition of resistance. This is exemplified by recent reports of multiple antibiotic resistance in Shigella strains in India, in Escherichia coli in India and Pakistan, and in nontyphoidal Salmonella (NTS) in South-East Asia. We propose to use deep metagenomic sequencing and genome level assembly to study the epidemiology of AMR in stools of children suffering from diarrhea. Here the epidemiology component will be surveillance and analysis of the microbial composition (to the bacterial species/strain level where possible) and its constituent antimicrobial resistance genetic elements (such as plasmids, integrons, transposons and other mobile genetic elements, or MGEs) in samples from a cohort where diarrhea is prevalent and antibiotic exposure is endemic. The goal will be to assess whether consortia of specific mobile antimicrobial resistance elements associate with species/strains and whether their presence is enhanced or amplified in diarrheal microbiomes and in the presence of antibiotic exposure. This work could potentially identify clonal complexes of organisms and MGEs with enhanced resistance and the potential to transfer this resistance to other enteric pathogens.</p> <p>We have performed WGS, metagenomic assembly and gene/protein mapping to examine and characterize the types of AMR genes and transfer elements (transposons, integrons, bacteriophage, plasmids) and their distribution in bacterial species and strains assembled from DNA isolated from diarrheal and non-diarrheal stools. The samples were acquired from a cohort of pediatric patients and controls from Colombia, South America where antibiotic use is prevalent. As a control, the distribution and abundance of AMR genes can be compared to published studies where resistome gene lists from healthy cohort sequences were compiled. Our approach is more epidemiologic in nature, as we plan to identify and catalogue antimicrobial elements on MGEs capable of spread through a local population and further we will, where possible, link mobile antimicrobial resistance elements with specific strains within the population.</p>
Project description:Impact of COVID-19-related nonpharmaceutical interventions on antimicrobial resistance and spectrum of non-typhoidal Salmonella: One Health approach
| PRJNA1019062 | ENA
Project description:Network Program on Antimicrobial Resistance, Superbugs and One Health
Project description:Diminished colonic health is associated with various age-related pathologies. In this study, we applied an integrative approach to reveal potential interactions between determinants of colonic health in aging C57BL/6J mice. Analysis of gut microbiota composition revealed an enrichment of various potential pathobionts, including Desulfovibrio spp., and a decline of the health-promoting Akkermansia spp. and Lactobacillus spp. during aging. Intraluminal concentrations of various metabolites varied between ages and we found evidence for an increased gut permeability at higher age. Colonic gene expression analysis suggested that during the early phase of aging (between 6 and 12 months), expression of genes involved in epithelial-to-mesenchymal transition and (re)organization of the extracellular matrix were increased. Differential expression of these genes was strongly correlated with Bifidobacterium spp. During the later phase of aging (between 12 and 28 months), gene expression profiles pointed towards a diminished antimicrobial defense and were correlated with an uncultured Gastranaerophilales spp. This study demonstrates that aging is associated with pronounced changes in gut microbiota composition and colonic gene expression. Furthermore, the strong correlations between specific bacterial genera and host gene expression may imply that orchestrated interactions take place in the vicinity of the colonic wall and potentially mediate colonic health during aging.
2018-05-09 | GSE113257 | GEO
Project description:transmission chain of oxazolidinone resistance genes through one health approach
| PRJNA948548 | ENA
Project description:Monitoring Antimicrobial Resistance in Bovine Feces from Farms across Lebanon: Sequencing and Genomic Surveillance under One Health
Project description:Salmonella enterica causes serious global burden of morbidity and mortality and is a major cause of infant bacteremia in sub Saharan Africa. Diseases caused by Salmonella are treatable with antibiotics but successful antibiotic treatment has become difficult due to antimicrobial resistance. An effective vaccine together with public health effort may therefore be a better strategy to control these infections. Protective immunity against Salmonella depends primarily on T cell-mediated immune responses and therefore identifying relevant T cell antigens is necessary for Salmonella vaccine development. Our laboratory has used an immunoproteomics approach to identify Chlamydia T cell antigens that exhibited significant protection against Chlamydia infection in mice. In this study, we infected murine bone marrow derived dendritic cells from C57BL/6 mice with Salmonella enterica strain SL1344 followed by isolation of MHC class I and II- molecules and elution of bound peptides. The sequences of the peptides were then identified using tandem mass spectrometry. We identified 87 MHC class II and 23 MHC class I Salmonella derived peptides. Four of 12 peptides stimulated IFN-? production by CD4 T cells from the spleens of mice with persistent Salmonella infection. These antigens will be useful for Salmonella immunobiology research and are potential Salmonella vaccine candidates.
2016-12-14 | PXD004451 | Pride
Project description:One Health Brazilian Resistance (OneBR)
Project description:Salmonella spp. biofilms have been implicated in persistence in the environment and plant surfaces. In addition, Salmonella is able to form biofilms on the surface on cholesterol gallstones. The ability of Salmonella spp. on these surfaces is superior to biofilm formation on surfaces on glass or plastic. Thus, we hypothesized that Salmonella gene expression is specific during biofilm development on cholesterol surfaces.