The dynamics of antimicrobial resistance genes in the pig and human gut microbiome in Uganda

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The proposed research aims to gain fundamental insight into the generation, sharing and transfer of antimicrobial resistance (AMR) genes within and between humans and their pigs under natural settings that represent different levels of antibiotic use/misuse. Defining these dynamics offers the best chance of developing effective control measures and underwrites the efforts toward limiting irrational antibiotic use in both human and animal health care.This study combines the use of current molecular techniques, efficiency in data processing and a setting of epidemiological relevance to detect antibiotic driven changes in the gut bacteria. A forensic investigation of each of these changes would then reveal the fundamental characteristics of AMR genes in the gut and their transfer potential across the pig-human interface. The hypothesis to be tested is that people in contact with pigs in peri-urban settings are at higher risk of acquiring AMR genes across this interface than people in rural settings.The specific objectives are:1. To identify significant changes in taxonomic and AMR genes in gut microbiomes of people and their pigs in peri urban and rural settings over a one-year period using 16SrRNA, AMR gene probes and real time PCR. 2. To conduct forensic investigations of the significant changes detected in objective 1 using sequence based metagenomics on the corresponding gut microbiomes in parallel with whole genome sequencing and phenotypic AMR testing of sentinel bacteria to understand the underlying dynamics. 3. To predict, estimate and make inferences on AMR gene occurrence, taxa-linked within and between host exchange and their potential phenotypic effects using bioinformatic, statistical and support vector machine approaches on the data generated in 1&2.