A Salmonella Virulence Factor Regulates Second Messenger Signaling and Effector Protein Expression via Proteolysis
Restricted (Penn State Only)
Author:
Kendra, Christopher
Graduate Program:
Biomedical Sciences (PHD)
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
June 01, 2023
Committee Members:
Christopher Norbury, Major Field Member Mauricio Pontes, Co-Chair & Dissertation Advisor Guy Townsend, Outside Unit Member Clare Sample, Co-Chair & Outside Field Member Ralph Keil, Program Head/Chair
Keywords:
Salmonella Proteolysis Cellulose second messenger virulence factors
Abstract:
Salmonella enterica is a facultative anaerobic, intracellular bacterium which causes gastroenteritis and, in some cases, severe systemic disease. To facilitate pathogenesis, S. enterica expresses various genes which encode proteins known as virulence factors. Virulence factors heighten bacterial fitness during host infection by inhibiting host antimicrobial processes and facilitate access to host tissues and resources. The critical virulence factor, MgtC, is necessary for growth during cytoplasmic magnesium starvation in laboratory media. Mutants of S. enterica lacking mgtC are unable to control phosphate uptake, harbor high intracellular levels of ATP and are translationally compromised. Additionally, the mgtC mutant is avirulent and overproduces cellulose biofilms during intracellular infection. In this thesis, I focus on defining the regulatory role of MgtC in repressing cellulose biosynthesis and promoting intracellular virulence. Findings from my work demonstrate a critical role of MgtC in maintaining cellular homeostasis through a post-translational mechanism. This mechanism enables a pro-virulence state in the bacterial cell by repressing c-di-GMP signaling and enabling the expression of virulence factors required for intracellular infection.
