Comparative proteomic analysis of wild type and mutant lacking histidine kinase BP1092 provide new insights into Bordetella pertussis virulence gene regulation

MARTINA DEBANDI; MARIELA CARRICA; CHRISTIAN HENTSCHKER; BRUNO BLANCÁ; JIMENA ALVAREZ HAYES; UWE VÖLKER; MARIA EUGENIA RODRIGUEZ; KRISTIN SURMANN; YANINA LAMBERTI

Congreso; LVIII Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research; 2022

Bordetella pertussis (Bp) is the etiological agent of whooping cough, a severe illness that is re-emerging even in highly vaccinatedpopulations. Previous studies have shown that Bp survives inside human macrophages, which probably contributes to persistenceand vaccine failure. Our group has shown that virulence factors play a key role in the Bp persistence inside host cells. Transcriptionof Bp virulence factors is controlled by the interrelated two-component systems (TCS) BvgAS and RisAK, which are involved ina phenotypic conversion between virulence and avirulence phases in response to environmental stimuli. Howerver, other yetunknown TCS could be involved in the adaptation of Bp to the intracellular environment. Through proteomics assays we show thatBP1092 is a TCS histidine kinase with increased protein levels upon internalization by a human macrophage cell line. Here, wefurther characterized the regulatory contribution of BP1092 under virulent and avirulent conditions by global proteomics. To thisend, we performed a 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 modulating (SS + 40 mMMgSO4) conditions.We found ten proteins with altered abundance between ΔBP1092 and wt or the trans-complemented strain, respectively, underavirulent conditions but none under control conditions. Among the proteins with different abundance (fold change >1.5, q1.5, q>0.05, p