A novel B. pertussis response regulator involved in the bacterial adaptation to low iron availability and intracellular survival

CARRICA, MARIELA; DEBANDI, MARTINA; ALVAREZ HAYES, JIMENA; LAMBERTI, YANINA; RODRIGUEZ, MARÍA EUGENIA

Simposio; 12th International Symposium on Bordetella; 2019

Pathogenic bacteria adapt to harsh conditions during the host infection mainly through two-component systems (TCS) that enable quick changes in gene expression. These systems are composed of a sensor, a histidine kinase (HK), that detects an environmental signal and phosphorylates a response regulator (RR) which finally binds promoter regions, in turns modulating gene expression. Bordetella spp. best characterized TCS is the BvgAS which regulates bacterial virulence. RisAK and PlrSR, are also TCS that act in coordination with BvgAS. To gain insight into the pertussis pathogenesis we previously studied the bacterial proteomic changes induced by two environments potentially relevant during infection. We analyzed the proteomic evolution of B. pertussis during intracellular infection of macrophages (THP1) and the bacterial response to low iron availability, a physiological stress that pathogens face in vivo. Our data showed that the adaptation to these environments included changes in abundance of BP3222, a potential RR, predicted as co-transcribed with RisK, recently described as the cognate HK of RisA. This genomic context suggests that BP3222 and RisA might share the same HK and be involved in the same regulatory network. In order to investigate the relevance of this RR we constructed a Bp in frame deletion mutant in the gene BP3222 (ΔBP3222). Comparative studies with THP1 cells infected with wtBp or ΔBP3222 showed that lack of this RR significantly decreased the bacterial intracellular survival. No significant differences between wtBp and ΔBP3222 growth in SS medium were observed suggesting a role of ΔBP3222 in bacterial adaptation to the intracellular environment. Comparative analysis of iron-starved wtBp and ΔBP3222 gene-expression profiles by qPCR showed that BP3222 regulates the expression of genes involved in iron acquisition and virulence which might explain the decrease in the intracellular survival and, more importantly, suggests a role of this RR in bacterial pathogenesis