Identification of OxyR as an activator of type 1 fimbriae () in serovar Typhi.

serovar Typhi (. Typhi) encodes 14 fimbrial gene clusters, including the mannose-binding type 1 fimbriae known as Fim. Type 1 fimbriae have been implicated in biofilm formation and adhesion to host cells in . However, their regulation in . Typhi remains largely unknown. To identify genes affecting the regulation of in . Typhi, we employed both a targeted and a genome-wide transposon-based screening approach. Overall, we identified 18 potential regulators of expression: 10 activators and 8 repressors. Two genes involved in the electron transport chain, and which encode the type II NADH dehydrogenase NDH-2, were identified. Both YqiC and NDH-2 contribute to the production of reactive oxygen species, prompting an investigation into the roles of oxidative stress response regulators OxyR and SoxR. We found that only OxyR regulates expression, which was specific to . Typhi. OxyR acts by directly binding to the promoter region. This study paves the way for future development of anti-adhesion strategies through the identification of 14 novel regulators for the most prominent fimbriae of . Typhi.IMPORTANCEAdhesion mediated by fimbriae is one of the critical steps in the infection process. Therefore, it is essential to better understand the regulation of type 1 fimbriae () in the human-specific pathogen serovar Typhi, the etiologic agent of typhoid fever. In this study, we identified 18 distinct mutants with altered regulation of . Furthermore, we confirmed that the DNA-binding protein OxyR directly regulates expression. Importantly, we also demonstrated regulatory differences in expression between . Typhi and . Typhimurium, as six of the genes identified altering expression in . Typhi either did not affect expression in . Typhimurium or had the contrary effect. This highlights fundamental differences between these serovars and emphasizes the need to investigate and compare aspects of gene regulation in . Typhi.