On the hunt for candidate genes involved in host-adaptation in Pseudomonas aeruginosa using comparative genomics

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen responsible for causing severe hospital-acquired infections, largely due to its adaptability, diverse range of virulence factors and drug resistance mechanisms. Despite extensive research, a substantial portion of the genome of P. aeruginosa remains functionally uncharacterized. The aim of this study was to identify candidate host-adaptation genes, including potential virulence factors, among these numerous uncharacterized genes. We performed a comparative genomic analysis of P. aeruginosa strains isolated from human clinical sources versus those from natural environments to identify clusters of homologous proteins significantly enriched with sequences from bacteria isolated from humans. Our analysis revealed that approximately 3% of all protein clusters showed significant enrichment in sequences from human isolates. Functional characterization of 45 selected clusters with particularly large enrichment of human isolates showed that these clusters contained genes with roles primarily related to host interaction and horizontal gene transfer. Notably, twelve of the 45 selected clusters consisted of genes with unknown function, suggesting the existence of potentially novel virulence factors or genes involved in the infection process within human-derived isolates. Our findings highlight specific uncharacterized protein clusters as promising targets for future investigation. The identification of both known virulence-associated functions and uncharacterized proteins among human-enriched clusters demonstrates the ability of our comparative genomics approach to detect established as well as potentially novel candidate host-adaptation genes. These findings further suggest that this strategy may be broadly applicable to the study of other opportunistic pathogens.