Abstract
Pathogens, which survive from stressed environmental conditions and evolve with antimicrobial resistance, cause millions of human diseases every year in the world. Fortunately, the NCBI Pathogen Detection Isolates Browser (NPDIB) collects the detected stress response genes and antimicrobial resistance genes in pathogen isolates sampled around the world. While several studies have been conducted to identify important antimicrobial resistance genes, little work has been done to analyze the stress response genes in the NPDIB database. In order to address this, this work conducted the first comprehensive statistical analysis of the stress response genes from five countries of the major residential continents, including the US, the UK, China, Australia, and South Africa. Principal component analysis was first conducted to project the stress response genes onto a two-dimensional space, and hierarchical clustering was then implemented to identify the outlier (i.e., important) genes that show high occurrences in the historical data from 2010 to 2020. Stress response genes and AMR genes were finally analyzed together to investigate the co-occurring relationship between these two types of genes. It turned out that seven genes were commonly found in all five countries (i.e., arsR, asr, merC, merP, merR, merT, and qacdelta1). Pathogens E. coli and Shigella, Salmonella enterica, and Klebsiella pneumoniae were the major pathogens carrying the stress response genes. The hierarchical clustering result showed that certain stress response genes and AMR genes were grouped together, including golT~golS and mdsB~mdsC, ymgB and mdtM, and qacEdelta1 and sul1. The occurrence analysis showed that the samples containing three stress response genes and three AMR genes had the highest detection frequency in the historical data. The findings of this work on the important stress response genes, along with their connection with AMR genes, could inform future drug development that targets stress response genes to weaken antimicrobial resistance pathogens.