Salmonella infection impacts host proteome thermal stability

Area of Science:

• Microbiology
• Proteomics
• Host-Pathogen Interactions

Background:

• Intracellular bacterial pathogens manipulate host cell machinery for survival.
• Salmonella enterica subsp. Typhimurium (STm) injects effector proteins to alter host protein function.
• Systematic, proteome-wide analysis of host protein functional changes during infection is challenging.

Purpose of the Study:

• To adapt and apply Thermal-Proteome Profiling (TPP) for systematic assessment of host protein abundance and thermal stability during STm infection.
• To differentiate between host protein changes induced by live STm versus non-viable STm.
• To identify specific host proteins and molecular interactions affected by STm infection.

Main Methods:

• Adaptation of Thermal-Proteome Profiling (TPP) for infection studies.
• Comparative analysis of host cells infected with live STm versus heat-killed STm.
• Integration of TPP data with host-pathogen protein-protein interaction databases.

Main Results:

• Most host protein abundance changes during STm infection occur independently of bacterial viability.
• Significant thermal stability changes in host proteins were specific to live STm infection.
• Identified thermal stability changes in mitochondrial proteins and Ifit1; discovered STm effector SteC destabilizes and phosphorylates Serbp1.

Conclusions:

• Measuring protein thermal stability is a powerful approach to study host-pathogen interactions.
• TPP can systematically uncover functional changes in host proteins during bacterial infections.
• This study revealed novel molecular interactions at the host-pathogen interface mediated by STm effectors.