Proteome analysis of BP1092 – a potential new virulence factor regulator in Bordetella pertussis

SURMANN, KRISTIN; DEBANDI, MARTINA; CARRICA, MARIELA; HENTSCHKER, CHRISTIAN; RODRIGUEZ, MARIA EUGENIA; VOLKER, UWE; LAMBERTI YANINA

Busan

Congreso; 22nd Human Proteome Organization World Congress (HUPO; 2023

Human Proteome Organization

BackgroundVirulence factors play a key role in Bordetella pertussis (Bp) persistence inside host cells. Virulence factor expression in Bp is controlled by the interrelated two-component systems (TCS) BvgAS and RisAK. There are hints that further, yet unknown, regulatory systems might be involved, too. BP1092 as TCS histidine kinase with increased protein levels upon internalization by a human macrophage cell line (Lamberti et al., JProteomics-2016) thus, is an interesting candidate for deeper analysis.MethodsWe first characterized the impact of BP1092 by global proteomics. To this end, we performed mass spectrometric analysis of Bp Tohama I wildtype (wt), an isogenic BP1092 deficient mutant (ΔBP1092), and ΔBP1092 trans-complemented with BP1092 (ΔBP1092 pBBR-BP1092) under control (SS) and virulence-modulating (SS + 40 mM MgSO4) conditions. Further, we used the three strains to infect THP-1 macrophages and determined bacterial survival as well as the host’s proteome after 24 h. ResultsIn total, we found eleven proteins with altered abundance between ΔBP1092 and wt or the trans-complemented strain, respectively. Among these eleven proteins, nine were related to virulence. Proteins with adhesion function FhaB, FhaC, and Cya had lower levels in the mutant compared to the wt under control conditions. Response regulator BvgAS and BvgR as well as FimC and toxins PtxAB showed lower levels in the mutant under modulating conditions. In addition, the wt and the complemented strain displayed a higher survival rate within THP-1 macrophages over 48 h. Consequently, almost 20 host proteins altered in level (fold change > |1.5|; q > 0.05) likewise after wt or complemented strain infection compared to mutant infection.ConclusionOur data of B. pertussis infection-mimicking models suggest that BP1092 may play a crucial role in fine-tuning of virulence factors to impact intracellular survival, thus revealing a new level of complexity of virulence regulations of Bp.