Comparative Genomic Analysis of Pseudomonas aeruginosa Isolates from Community-Acquired and Hospital-Acquired Pneumonia

Purpose: To characterize the genomic features of Pseudomonas aeruginosa isolates causing community-acquired pneumonia (CAP) and compare them with hospital-acquired pneumonia (HAP) genomes to identify setting-associated genetic determinants. Patients and Methods: Three CAP isolates collected in China underwent antimicrobial susceptibility testing and whole-genome sequencing. Comparative genomic analyses were performed against 84 complete HAP-associated genomes retrieved from NCBI RefSeq (accessed in December 2023), including core genome SNP phylogeny, profiling of antimicrobial resistance (AMR) determinants, virulence genes, and pangenome analysis to identify CAP-specific genes. Results: The three CAP cases presented with severe pneumonia (including septic shock), with one fatality; however, all CAP isolates remained susceptible to the most commonly used antipseudomonal agents. CAP genomes were 6.5– 7.1 Mb (GC 65.76– 66.41%) and contained 5908– 6633 predicted coding sequences. Core-SNP phylogeny showed clustering of the three CAP isolates. Compared with HAP genomes, CAP isolates harbored fewer acquired AMR genes and fewer resistance-associated mutations. Virulence profiling identified a subset of virulence genes absent from all CAP genomes (n = 40), largely annotated as immune modulation and including loci consistent with highly variable surface polysaccharide regions, together with several genes annotated to biofilm-related functions and effector delivery systems. Major type III secretion system effector profiles differed across CAP isolates ( exoU in one isolate; exoS in two). Pangenome analysis identified 10,225 gene families, and 157 genes were specific to the CAP isolates, most encoding hypothetical proteins, with a subset related to lipid transport and metabolism, including fatty acid uptake and functions associated with β-oxidation. Given the limited number of CAP isolates, comparisons between groups are descriptive. Conclusion: CAP-associated P. aeruginosa showed a distinct comparative genomic profile with reduced AMR determinant burden and a distinct virulence gene repertoire despite severe clinical presentation. CAP-specific genes, including those linked to lipid metabolism, may contribute to niche adaptation and warrant functional validation. Keywords: Pseudomonas aeruginosa , community-acquired pneumonia, hospital-acquired pneumonia, comparative genomics, virulence, antimicrobial resistance