A novel B. pertussisresponse regulator involved in the bacterialadaptation to low iron availability andintracellular survival

CARRICA M; CAFIERO H; DEBANDI M; ALVAREZ HAYES J; LAMBERTI Y; RODRÍGUEZ M E

Brusellas

Simposio; 12th International Symposium on Bordetella; 2019

Pathogenic bacteria adapt to harsh conditions during the host infectionmainly throughtwo-component systems (TCS) that enable quick changes in gene expression. These systems are composed of a sensor, a histidine kinase (HK), that detectsan 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 regulatesbacterial 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 twoenvironmentspotentially relevant during infection. We analyzed the proteomic evolution of B. pertussisduring intracellular infection of macrophages (THP1)and the bacterial response to low iron availability, a physiological stressthat pathogens face in vivo.Our data showed that the adaptation to these environments included changes in abundance of BP3222, a potential RR,predicted asco-transcribed with RisK, recently described as the cognate HK of RisA. This genomic context suggests that BP3222 and RisAmight share the same HK and be involved in the same regulatory network.In order to investigate the relevance of this RR we constructed aBpin frame deletion mutant in the gene BP3222 (ΔBP3222).Comparative studies with THP1 cells infected with wtBp or ΔBP3222showed thatlack of this RR significantly decreasedthe bacterialintracellular survival. No significant differences betweenwtBp 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 qPCRshowed that BP3222 regulates the expression of genes involved in iron acquisitionand virulence which might explain the decrease in the intracellular survival and, more importantly, suggestsarole of this RR in bacterial pathogenesis.