Changes in potential pathogenicity-associated proteins of Helicobacter cinaedi upon infection of macrophage cells
A K Voronina1, B A Efimov1,2, M V Malakhova1
1Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia.
Introduction:
Helicobacter cinaedi is a spiral-shaped Gram-negative, enterohepatic bacterium classified as a conditional pathogen (pathogenicity group 2). It is known to cause bacteremia and a variety of other diseases in humans. In particular, Helicobacter cinaedi has been shown to impair intracellular cholesterol metabolism when interacting with macrophages, leading to foam cell formation. M1-macrophages transformed into the foam cell phenotype contribute to atherosclerotic plaques, suggesting a potential link between H. cinaedi infection and atherosclerosis development.
Methods:
To uncover protein factors involved in H. cinaedi pathogenesis, we performed a detailed mass spectrometric analysis of the proteome of strain BAA-847. This study represents the first comprehensive analysis of the bacterium's proteome under standard culture conditions and after infection of M1-type macrophage cells.
Results:
We identified 1,575 proteins in the H. cinaedi proteome, 109 of which were differentially upregulated after macrophage infection. Functional analysis revealed roles for these proteins in immune evasion, intracellular survival, and potential pathogenicity. Beyond known virulence factors (HcaA, Cdt, AhpC), we identified poorly characterized proteins with toxic or immunomodulatory functions. Notably, some upregulated proteins enable cholesterol utilization as a carbon source, while others may participate in a toxin injection mechanism disrupting host cell metabolism-potentially linked to foam cell formation.
Conclusion:
Our findings provide new insights into H. cinaedi pathogenicity, highlighting previously unexplored virulence mechanisms. The identified proteins could serve as targets for further research into H. cinaedi-associated diseases, including atherosclerosis.
Insights
Helicobacter cinaedi infection impairs macrophage cholesterol metabolism, contributing to atherosclerosis. This study identifies novel bacterial proteins involved in H. cinaedi pathogenesis and virulence.
Area of Science:
- Microbiology
- Immunology
- Pathogenesis
Background:
- Helicobacter cinaedi is a Gram-negative bacterium causing human diseases like bacteremia.
- H. cinaedi infection impairs macrophage cholesterol metabolism, potentially linking it to atherosclerosis via foam cell formation.
Purpose of the Study:
- To identify protein factors contributing to H. cinaedi pathogenesis.
- To comprehensively analyze the H. cinaedi proteome under standard and infected macrophage conditions.
Main Methods:
- Mass spectrometric analysis of H. cinaedi proteome (strain BAA-847).
- Proteomic analysis under standard culture and M1-macrophage infection conditions.
Main Results:
- Identified 1,575 H. cinaedi proteins; 109 were upregulated post-macrophage infection.
- Upregulated proteins are involved in immune evasion, intracellular survival, and pathogenicity.
- Discovered novel proteins potentially involved in cholesterol utilization and toxin injection, linked to foam cell formation.
Conclusions:
- New insights into H. cinaedi virulence mechanisms and pathogenicity.
- Identified proteins offer potential targets for research into H. cinaedi-associated diseases, including atherosclerosis.
