Abstract Salmonella enterica serovar Typhimurium persists across environments and causes disease by coordinating biofilm formation and host invasion. Although PagN is a known adhesin and invasin, its role in regulating these processes is unclear. We investigated PagN’s contribution to biofilm development and pathogenicity using a chromosomal pagN deletion mutant (ΔpagN) and a complemented strain. Deletion did not affect growth but significantly reduced biofilm formation on polystyrene at 20°C and 28°C. The mutant showed altered morphotypes, reduced cellulose, impaired pellicle formation, delayed autoaggregation, and restricted motility. In Caco-2 cells, pagN loss reduced adhesion by ∼60% and abolished invasion by 90%. Ectopic expression of pagN successfully abrogated phenotypic shifts, confirming gene specificity. Comparative transcriptomics revealed a niche-specific regulatory footprint; the profound hilA (SPI-1) repression in planktonic cultures was not recapitulated in biofilms. Instead, the mutant exhibited targeted csgD-yaiC attenuation during biofilm development, alongside robust fimF induction, indicating a potential compensatory shift in the adhesive landscape. Network analysis suggests PagN is integrated into global circuits, influencing pathways through the regulator of capsule synthesis (Rcs) system. These findings demonstrate PagN is a key determinant linking biofilm development with virulence regulation in S. Typhimurium, coordinating environmental persistence and host–pathogen interaction.
Karaca et al. (Wed,) studied this question.