Proteomic Profiling of Surgical Site Infection Pathogens in Nigerian Tertiary Hospitals: Implications for Novel Antimicrobial Strategies

The rising burden of multidrug-resistant surgical site infection (SSI) pathogens in Nigerian hospitals demands innovative antimicrobial strategies beyond conventional antibiotic regimens. Proteomic profiling of SSI pathogens can reveal novel virulence factors and potential drug targets. This dissertation performs the first proteomic characterization of predominant SSI pathogens from Nigerian tertiary hospitals, seeking to identify novel antimicrobial targets and inform future drug development. Wound swab samples yielding significant bacterial growth were collected from 300 SSI cases at hospitals in Lagos (South West), Kano (North West), and Enugu (South East) from 2020 to 2023. Proteomic analysis was performed using two-dimensional gel electrophoresis and label-free quantitative mass spectrometry. Differentially expressed proteins between drug-susceptible and drug-resistant isolates were identified and mapped to virulence and resistance pathways. Staphylococcus aureus and Klebsiella pneumoniae were the most common pathogens. Proteomic analysis identified novel overexpressed proteins in MRSA isolates including biofilm-associated surface proteins (IsdA, SasG) and resistance-associated secreted proteases. Klebsiella pneumoniae isolates showed upregulation of outer membrane proteins linked to carbapenem efflux. Seventeen candidate drug target proteins were identified, with three demonstrating no human homologs. The dissertation establishes a proteomic SSI pathogen database as an original scientific contribution and recommends international collaboration for translational antimicrobial development targeting the identified protein candidates. Keywords: proteomics, surgical site infection, antimicrobial resistance, MRSA, drug targets