Campylobacter jejuni Virulence Factors Identified by Modulating Their Synthesis on Ribosomes With Altered rRNA...

Area of Science:

• Microbiology
• Molecular Biology
• Pathogenesis

Background:

• Campylobacter jejuni is a primary cause of foodborne illness globally, responsible for gastroenteritis and intestinal issues.
• Bacterial virulence, including adhesion, host survival, and disease induction, relies on pathogen-synthesized virulence factors via ribosomes.
• Ribosome modification is a potential target for controlling bacterial infections.

Purpose of the Study:

• To investigate the impact of altering ribosome methylation on C. jejuni virulence.
• To identify essential factors for C. jejuni infection and pathogenesis by disrupting ribosome function.
• To demonstrate a novel approach for discovering bacterial virulence determinants.

Main Methods:

• Inactivation of the Cj0588/TlyA methyltransferase in C. jejuni to prevent rRNA methylation.
• Assessment of bacterial phenotypes, including biofilm formation, host cell adhesion, invasion, and survival.
• Proteomic analysis using mass spectrometry to identify changes in protein composition.
• Gene inactivation of identified virulence factors (cdtC, mlaEFD) to confirm their roles.

Main Results:

• Inactivation of TlyA significantly reduced C. jejuni virulence, impairing biofilm formation, host cell attachment, invasion, survival, and immune response.
• Proteomic analysis revealed decreased levels of cytolethal distending toxin (CdtC) and MlaEFD proteins involved in outer membrane vesicle production.
• Confirmation that CdtC and MlaEFD proteins are crucial for establishing infection.

Conclusions:

• Altering ribosome methylation is an effective strategy to attenuate C. jejuni virulence.
• This approach successfully identified key virulence factors, including CdtC and MlaEFD, essential for campylobacteriosis.
• Ribosome-targeted strategies offer a promising avenue for discovering and combating bacterial pathogens.