Changes in Potential Pathogenicity-Associated Proteins of Helicobacter cinaedi Upon Infection of Macrophage Cells Authors

Alice K Voronina^1*Boris Efimov²Maja Malakhova¹Polina Shnaider¹Olga Ivanova¹M E Bogomyakova¹V O Shender^1,3Maria Lagarkova¹G P Arapidi^1,3,4

• ¹Federal Scientific Clinical Center of Physical and Chemical Medicine, Federal Medical & Biological Agency of Russia, Moscow, Russia
• ²Federal State Autonomous Educational Institution of Higher Education “N.I. Pirogov Russian National Research Medical University” of the Ministry of Health of the Russian Federation, Moscow, Russia
• ³Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia
• ⁴Moscow Institute of Physics and Technology (National Research University), Dolgoprudny, Russia

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 2 particular, Helicobacter cinaedi has been shown to cause impaired intracellular cholesterol metabolism when interacting with macrophages, leading to the foam cells formation. M1-macrophages transformed into the foam cells phenotype form the basis of atherosclerotic plaques, as a result of which Helicobacter cinaedi-associated atherosclerosis may develop. To uncover protein factors involved in the pathogenesis of Helicobacter cinaedi, we performed a detailed mass spectrometric analysis of the proteome of strain BAA-847. To the best of our knowledge, this is the first such comprehensive study examining the bacterium's protein profile both under standard culture conditions and after infection of M1-type macrophage cells. We identified 1,575 proteins in the Helicobacter cinaedi proteome, and of these, 109 proteins were differentially upregulated after infection of macrophage cells. For these proteins, we performed a detailed functional analysis and proposed a model to explain their potential roles during Helicobacter cinaedi infection. In addition to the known pathogenicity factors HcaA, Cdt, and AhpC, we discovered several poorly understood proteins that are involved in immune response evasion, adaptation for survival within host cells, and possess toxic or other potentially pathogenic functions. Among the differentially upregulated proteins, we found those that enable the bacterium to utilize intracellular cholesterol as a carbon source. Additionally, we identified proteins involved in a toxin injection mechanism that disrupts host cell metabolism, which may be linked to the foam cell formation induced by Helicobacter cinaedi.