Abiola, I.2020-11-232020-11-232019-07http://ugspace.ug.edu.gh/handle/123456789/35880PhD. Molecular Cell Biology of Infectious DiseasesHospitals are hubs for transmission of different pathogens. In Ghana, little is known about the diversity and antimicrobial resistance (AMR) profiles of bacterial pathogens from hospital environments. Essential is also the rising challenges of antimicrobial heteroresistance, which has contributed to the increase in bacterial AMR. In this study, bacterial strains were isolated from air and fomites of the Intensive Care Unit (ICU) and characterized with phenotypic and molecular techniques. Bacterial AMR profiles to conventional and last resort antibiotics were determined with agar disc diffusion and micro-broth dilution assays. Antimicrobial heteroresistance to polymyxins was determined using E-test and population analysis profiling assays. Galleria mellonella infection (GMI) model was employed to evaluate the virulence and pathogenicity of the identified bacterial strains. Lipopolysaccharides (LPS) was analyzed and profiled using Sodium Dodecyl Sulfate (SDS-PAGE) and matrix assisted laser desorption ionization-time of flight (MALDI-TOF) Mass Spectrometry analysis. AMR markers and LPS-modifying genes were characterized using specific primers targeted Polymerase Chain Reaction (PCR) and sequencing. Our findings confirmed that there is diversity of Gram-Positive and Gram-negative bacteria with high (> 80%) level of resistance to conventional and last resort antibiotics in sampled Ghanaian hospital environments. Majority of these strains are hereroresistant phenotypes and are highly virulent and pathogenic in GMI. The mechanisms of AMR to conventional antibiotics were associated with the presence of resistance markers (such as β-lactamases, quinolone resistant, gyrase, KPC carbapenemase, methicillin, aminoglycosides and macrolide efflux genes). The resistance of the strains to polymyxins (B and E) are on account of LPS modifications, especially with the identifications of the LPS modifying markers, PhoP, PhoQ, PmrA and PrmB. The structural differences in the lipid A moieties reported in this study are possible pointers to mechanisms of resistance exhibited by these strains. Overall, this study provides evidence on the potential high risk associated with bacteria in Ghanaian hospital environments.enAntimicrobial Resistance (AMR)VirulenceHospitalBacteriaThesis