Sequence Variation and Structural Insights into Porin Genes (OmpF, OmpC) of Wastewater-Derived <i>Escherichia coli</i> : A Molecular and Bioinformatics Approach

Multi-drug-resistant Escherichia coli is one of the most common waterborne pathogens, causing severe illnesses with limited treatment options. Hospital wastewater effluents containing unused and excreted drugs, including antibiotics, are considered the primary contributors to multidrug resistance in microorganisms. This wastewater is directly released into the environment, contaminating water sources. The study aimed to assess the occurrence, molecular and in silico characterization of antibiotic-resistant genes in E. coli isolated from three tertiary care units in Peshawar. Among the total 462 collected samples, 111 samples were positive for E. coli. These strains exhibited resistance to Ampicillin, Gentamycin, Tetracycline, Cefazolin, Ciprofloxacin, Penicillin, Cefepime, Ceftriaxone, Imipenem, Meronem, Amikacin, Norfloxacin, Fosfomycin, Levofloxacin, Tobramycin, Chloramphenicol, Colistin and Tigecycline, while varying susceptibility was shown to tigecycline, Fosfomycin, chloramphenicol and colistin. Among the resistant isolates (n [Formula: see text] 33), 18% of the isolates expressed OmpC, while OmpF was detected in 36% of the isolates. Following PCR, the products were subjected to next-generation sequencing due to its high accuracy in detecting mutations. Genetic analysis revealed G13E and G116E mutations in OmpF, while A239V and R292 L mutations were detected in OmpC. The conformational stability of wild and mutated proteins was estimated using a 100 ns molecular dynamics simulation. In brief, this study focused on discovering promising chemical entities that could support the development of in silico drug candidates targeting antibiotic-resistant strains of E. coli.