This dissertation reports prevalence, serotype distribution and phenotypic and genotypicrncharacteristics of non-typhoidal Salmonella (NTS) in humans and animals in centralrnEthiopia and effect of small molecule adenosine mimetic compounds on Salmonella biofilmrnformation. Farm level and animal level Salmonella prevalence was (7.6%, 2.3%) in dairy;rn(14.6%, 4.7%) in poultry; and (42.6%, 4.4%) in swine farms. The prevalence was 7.2% inrndiarrheic patients from primary health centers and 2.1% from hospitals. S.Typhimuriumrn(27.6%) was the most frequently isolated serotype, followed by S. Saintpaul (21.7%), S.rnVirchow (18.4%) and S. Kentucky (6.6%). Salmonella isolation was significantly associatedrnwith detection of diarrhea in dairy cattle (p=0.012), and consumption of raw vegetables inrnhumans (OR=1.91, 95% CI=1.29-2.83, Ï‡2=4.74, p=0.025). Drug resistance was morerncommon in dairy farms in Addis Ababa than outside (p=0.009) and overall antimicrobialrnresistance was more common in animals than in humans. Clonally related genotypes ofrnS.Virchow, S.Typhimurium, S.Kentucky, S.Braendurp and S. Miami were circulating amongrnhumans and animals as determined by pulsed-field gel electrophoresis (PFGE). MLSTrnanalysis showed 3 novel allele types and 5 novel sequence types among 21 strains examined.rnThe dominant beta-lactamase enzyme was blaTEM type. BlaOXA10 and blaCTX-15 wererndetected only in a single MDR S. Concord strain. Double mutation in gyrA (Ser83-Phe andrnAsp87-Gly) as well as parC (Thr57-Ser + Ser80-Ile) subunits of quinolone resistancerndetermining region (QRDR) was the primary mechanism for resistance to quinolones andrnwas detected in all S. Kentucky isolates resistant to both nalidixic acid and ciprofloxacinrnfrom animals (n=8) and humans (n=2). Although decreased susceptibility to ciprofloxacinrnand/or nalidixic acid was observed in some isolates, no mutation in QRDR nor plasmidrnmediated quinolone resistance (PMQR) genes were detected. Majority of Salmonellarniirnisolates exhibited robust biofilm formation (89%) and displayed red dry and rough (RDAR)rnmorphotype. Detection of class 1 integron was correlated with expression of multicellularrnbehavior and the extent of MDR. Screening of an ATP-mimetic library, gave a singlerncompound (7955004) capable of significant inhibition of Salmonella enterica andrnAcinetobacter baumannii biofilm formation. The compound was not bactericidal orrnbacteriostatic toward S. Typhimurium nor cytotoxic to mammalian cells. GroEL and DeoDrnwere found to be the potential protein-binding targets of the compound as identified byrnATP-sepharose affinity matrix. Circulation of clonally related NTS serotypes in foodrnanimals and humans, abundance of MDR in isolates from food animals, co-dominance ofrnMDR and multicellular behavior in Salmonella isolates in the study area, increased the riskrnof spreading resistant Salmonella strains and resistance genes to human population.rnIntegrated surveillance of NTS in humans and animals and implementation of appropriaternpathogen control strategy along critical points in food animal production from farm to benchrnis recommended. The identification of a lead compound with biofilm inhibitory capabilitiesrntoward Salmonella provides a potential new avenue of therapeutic intervention againstrnSalmonella and other bacterial pathogens. Further activity guided evaluation of compoundrn7955004 and its derivatives with the goal of increasing its potency and broadening itsrnspectrum of activity against additional biofilm forming pathogens should be conducted.rnKey words: Antimicrobial resistance, Biofilm, Non-typhoidal Salmonella, Prevalence,rnSerotype