Species-Specific Stress Responses to Selenium Nanoparticles in Pseudomonas aeruginosa and Proteus mirabilis

Urinary tract infections (UTIs) remain a major global health concern, with rising antimicrobial resistance prompting the search for alternative therapies. Selenium nanoparticles (Se NPs) are promising antimicrobial agents due to their unique physicochemical properties and ability to disrupt bacterial physiology. This study evaluated the antibacterial efficacy of Se NPs against four uropathogens and conducted comparative proteomic analyses to elucidate stress responses. Enumeration assays showed that Se NPs effectively inhibited bacterial growth, with <i>Pseudomonas aeruginosa</i> being the most susceptible and <i>Proteus mirabilis</i> the most resistant. Microscopy revealed Se NP-induced membrane rupture and cellular deformation across all species. Proteomic and bioinformatic analyses showed more pronounced protein regulation in <i>P. mirabilis</i> than in <i>P. aeruginosa</i>. Cluster of Orthologous Groups (COG) analysis revealed both shared and species-specific responses, while Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated activation of key stress pathways. Virulence-associated proteins were modulated in both species, with <i>P. mirabilis</i> uniquely upregulating stress survival and exotoxin-related proteins. Both regulated efflux pumps, suggesting active transport mitigates Se NP toxicity. <i>P. aeruginosa</i> showed mercury resistance, while <i>P. mirabilis</i> expressed tellurite resistance proteins. These findings highlight distinct yet overlapping strategies and support the potential of Se NPs in novel antimicrobial development.