Keywords

small non-coding RNA, iron homeostasis, Salmonella Typhimurium

Abstract

Iron is an essential element for most bacteria as it is a crucial cofactor for enzymes involved in fundamental reactions such as DNA synthesis. Despite being the fourth most abundant element on Earth, bacteria face challenges acquiring iron under aerobic conditions due to the poor solubility of its oxidized form (Fe³⁺). To overcome this, bacteria have developed various strategies of iron acquisition, such as the production of siderophores. Siderophores are small molecules that scavenge free Fe³⁺ in iron-deprived environments. Iron acquisition is tightly regulated due to its capability of promoting hydrogen peroxide formation via the Fenton reaction. In Salmonella Typhimurium, the transcriptional regulator Fur and the small RNAs RyhB-1 and RyhB-2 are master regulators of iron homeostasis. Under iron-rich conditions, ferrous iron binds to Fur, repressing the transcription of iron acquisition genes and of ryhB-1 and ryhB-2 genes. In contrast, under iron-poor conditions, Fur is inactive, which results in the expression of siderophore genes and of RyhB-1/2 that post-transcriptionally repress genes encoding non-essential iron-using proteins and promote siderophore synthesis.

Despite our extensive knowledge of iron homeostasis in Salmonella, some genes of the Fur and RyhB-1/2 regulons still resist functional characterization. This is the case of yncE (STM14_1918 in S. Typhimurium) that is repressed by Fur in the presence of iron and predicted to be activated by RyhB upon iron starvation in E. coli. Previous studies have demonstrated that the YncE protein is contained in outer membrane vesicles (OMVs) and that it contributes to S. Typhimurium’s survival inside host macrophages that are iron-deprived. Here, I demonstrate that RyhB-1/2 are essential for YncE expression during iron starvation and that both small RNAs directly activate yncE. My future work aims at elucidating the function of YncE that we hypothesize plays a key role in promoting iron acquisition during infection.

Thesis Completion Year

2025

Thesis Completion Semester

Spring

Thesis Chair

Salvail, Hubert

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Thesis Discipline

Biomedical Sciences

Language

English

Access Status

Campus Access

Length of Campus Access

1 year

Campus Location

Orlando (Main) Campus

Restricted to the UCF community until 5-15-2026; it will then be open access.

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Rights Statement

In Copyright