Antibiotic resistance genes
Antibiotic resistance gene pool estimation through metagenomic approach
Tech Area / Field
- BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
3 Approved without Funding
Armenian State Agrarian University, Armenia, Yerevan
- Tohoku University / Tohoku University School of Medicine, Japan, Sendai\nGeorgia Institute of Technology / School of Biology, USA, GA, Atlanta\nInstitut Pasteur, France, Paris\nAgriculture and Agri-Food Canada, Canada, ON, Ottawa\nMcMaster University, Canada, ON, Hamilton
Project summaryThe emergence of multidrug-resistant bacterial strains such as Mycobacterium tuberculosis (causative agent of tuberculosis), Streptococcus pneumoniae (pneumonia, ear infections, and meningitis), Enterococcus species (hospital infections), Staphylococcus aureus (skin, bone, lung, and bloodstream infections), Klebsiella (infections in health care settings), Salmonella (foodborne infections), Escherichia coli (urinary tract infections), and other infective agents has immense clinical and societal implications: for example, about 100,000 annual deaths in Europe resulted from inappropriate antibiotic treatment of patients with severe infections and about 15% of patients in European hospitals acquire multi-drug resistant infections. Thus, retaining the efficacy of newer antibiotics entering the clinical practice is vital to control these infections. In this proposal, we will address the question “What kind of antibiotic use practices may accelerate the appearance of resistance to newer antibiotics?” We suggest that the frequency of resistances to newer antibiotics may be higher in communities with less controlled antibiotic use. We will test the hypothesis that in communities with uncontrolled use of antibiotics the pool of antibiotic resistance genes is larger, thus increasing the probability of mutations/transpositions/transfers leading to resistance to newer antibiotics. Experimentally, the pool of these new mutant alleles will be estimated through the metagenomic analysis of fecal samples from two cohorts of communities, with controlled and uncontrolled use of antibiotics. The metagenome libraries will be tested for resistance to newer antibiotics and the corresponding genes identified through transposon mutagenesis, deletion analysis, and sequencing. Genetic transfer potential of these genes will be evaluated by sequence analysis of surrounding regions as well as in conjugation experiments. The frequency and the possibility of dissemination of these genes will be through quantitative real-time PCR detection in fecal samples, sewage water, and environmental samples. This proposal is in lines with the general strategy to protect public health by identification of antibiotic use practices leading to the appearance and dissemination of genes conferring resistance to newer antibiotics. Results obtained are intended for use in early warning monitoring efforts to prevent the transmission of these resistance genes to human and animal pathogens. Data generated in this study will provide background information for recommendations on the antibiotic use policy.
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