The Genetic Compatibility between Antibiotic Resistance Genes and Bacterial Hosts: Evaluated by measuring differences in k-mer distributions and comparing gene codon usage with tRNA availability

Abstract

Antibiotic resistance is a growing global health concern, driven by bacteria exchanging antibiotic resistance genes (ARGs) through horizontal gene transfer. The factors influencing the spread of ARGs across bacteria are not entirely understood, though genetic compatibility has been proposed as a contributing factor. This project aimed to explore genetic compatibility between ARGs and bacterial genomes by creating two metrics. The first metric, the 5mer score, was created by looking at nucleotide composition, specifically comparing 5-mer distributions using Euclidean distance. The second metric, the tRNA score, was created by comparing codon usage in the genes with the tRNA availability in the bacterial hosts. The results showed that both scores capture certain aspects of genetic compatibility and that higher compatibility correlates with increased likelihood of horizontal gene transfer. Although some transfers have occurred with poor scores, this suggests that transfers can still take place despite lower genetic compatibility, for example under evolutionary pressure. Gene length was identified as an important factor to take into account when working with 5-mers. Further studies include implementing the 5mer score in machine learning to determine the spread of ARGs, and refining the tRNA score due to its limitations, including how the scores were determined.