From Environmental Persistence to Host Adaptation: Differential Curli Regulation in Salmonella enterica Serovars Typhimurium and Typhi.

Salmonella enterica comprises numerous serovars with distinct host ranges and disease outcomes. Among them, Salmonella enterica serovar Typhimurium (S. Typhimurium) is a leading cause of gastroenteritis worldwide. Its ability to persist both in the environment and within the host gastrointestinal tract is largely attributed to biofilm formation. In contrast, the human-restricted pathogen Salmonella enterica serovar Typhi (S. Typhi) primarily forms biofilm in the gallbladder during chronic infection. These differences suggest that the two serovars are exposed and respond to distinct environmental cues. Curli fimbriae are key components of the biofilm matrix, contributing to initial surface adhesion and structural stability. In this review, we examine the regulation of curli fimbriae (csg operons) in S. Typhimurium, incorporating recent advances in the field, and compare these mechanisms with new insights concerning regulation in S. Typhi. Comparative analyses highlight significant differences in csg expression and regulatory pathways between the two serovars. All two-component systems known to influence curli expression carry mutations in active protein domains in S. Typhi. This is also true for diguanylate cyclases and phosphodiesterases, with some exhibiting important modifications in S. Typhi, including truncation and insertion. Such polymorphisms could contribute to variation in the curli regulatory pathway and may reflect broader mechanisms of host adaptation in S. Typhi. Understanding this regulatory divergence is essential for elucidating host specificity and the distinct pathogenic strategies of S. Typhi related to biofilm formation.