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

DEBANDI, MARTINA; CARRICA, MARIELA; HENTSCHKER, CHRISTIAN; BLANCÁ, BRUNO; ALVARES HAYES, JIMENA; RODRIGUEZ, MARIA EUGENIA; VOLKER, UWE; SURMANN KRISTIN; LAMBERTI, YANINA

Mendoza

Congreso; LVIII Congreso de la Sociedad Argentina de Investigaciones Bioquímicas (SAIB).; 2022

Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular

ordetella pertussis (Bp) is the etiological agent of whooping cough, a severe illness that is re-emerging even in highly vaccinated populations. Previous studies have shown that Bp survives inside human macrophages, which probably contributes to persistence and vaccine failure. Our group has shown that virulence factors play a key role in the Bp persistence inside host cells. Transcription of Bp virulence factors is controlled by the interrelated two-component systems (TCS) BvgAS and RisAK, which are involved in a phenotypic conversion between virulence and avirulence phases in response to environmental stimuli. Howerver, other yet unknown TCS could be involved in the adaptation of Bp to the intracellular environment. Through proteomics assays we show that BP1092 is a TCS histidine kinase with increased protein levels upon internalization by a human macrophage cell line. Here, we further characterized the regulatory contribution of BP1092 under virulent and avirulent conditions by global proteomics. To this end, 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 mM MgSO4) conditions.We found ten proteins with altered abundance between ΔBP1092 and wt or the trans-complemented strain, respectively, under avirulent conditions but none under control conditions. Among the proteins with different abundance (fold change >1.5, q1.5, q>0.05, p