COMPARATIVE GENOMIC ANALYSIS OF ANTIBIOTIC RESISTANCE MECHANISMS IN PATHOGENIC BACTERIA

Abstract

In this work, there is an inquiry of the genetic determinants of antibiotic resistance in the generic pathogenic bacteria, and a comparative genomic design has been adopted to choose resistance determinants, pattern of mutation, and gene transfer systems. The NCBI database was searched and 45 clinical isolates (Escherichia coli (n = 15), Staphylococcus aureus (n = 15) and Pseudomonas aeruginosa (n = 15)) were annotated with Prokka with their whole-genome sequences downloaded. Each genome contained between 3, 250 and 5,870 protein-coding genes, and the GC content of 32.8 -66.2%. The screening of the antibiotic resistance genes with CARD and ResFinder identified 142 different resistance genes, 61% of which were common to multiple species, and 39% of the genes were species-specific. The most common resistance genes were 0 -lactamase genes (78% of isolates), followed by efflux genes and aminoglycoside resistance genes, respectively. Verification of comparative resistome analysis indicated that the core resistance genes formed about 58 % of the entire resistome, and accessory genes formed about 42 %. Frank SNP analysis revealed 1,240 significant mutations in important target genes of which 27 were determined to directly correlate with resistance phenotype. Phylogeny analysis presented consistency in clustering with the resistance profiles with the mean bootstrap value of 91. The study in horizontal gene transfer showed that 73% of the isolates had plasmid based resistance genes, 46% of genomes had integrons, which showed that the dissemination of genes is active. On the whole, the findings show that a complex of conserved resistome factors, evolution-induced mutation adjustments, and widespread horizontal gene transfer contribute to the growth of antibiotic resistance in pathogenic bacteria and the necessity of comparing genomics in comprehending resistance evolution and in designing therapeutic antimicrobial approaches.