Combinatorial control of adhesion of Brucella abortus 2308 to host cells by transcriptional rewiring of the trimeric autotransporter btaE

RODRIGO SIEIRA; MAGALÍ G. BIALER; MARA S. ROSET; VERÓNICA RUIZ-RANWEZ; TOMÁS LANGER; GASTÓN M. AROCENA; ESTEFANÍA MANCINI; ANGELES ZORREGUIETA

MOLECULAR MICROBIOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2017

0950-382X

p { margin-bottom: 0.1in; direction: ltr; color: rgb(0, 0, 10); line-height: 120%; text-align: left; }p.western { font-family: "Times New Roman",serif; font-size: 12pt; }p.cjk { font-family: "Times New Roman",serif; font-size: 12pt; }p.ctl { font-family: "Times New Roman",serif; font-size: 12pt; }a:link { color: rgb(0, 0, 255); }Regulatory network plasticity is a key attributeunderlying changes in bacterial gene expression and a source ofphenotypic diversity to interact with the surrounding environment.Here, we sought to study the transcriptional circuit of HutC, aregulator of both metabolic and virulence genes of the facultativeintracellular pathogen Brucella.Using in silico andbiochemical approaches, we identified a novel functional HutC-bindingsite upstream of btaE,a trimeric-autotransporter adhesin involved in the attachment ofBrucellato host extracellular matrix components. Moreover, we identified twoadditional regulators, one of which, MdrA, acts in concert with HutCto exert a combinatorial control of both btaEpromoter activity and attachment of Brucellato HeLa cells. Analysis of btaEpromoter sequences of different species indicatedthat this HutC-binding site was generated denovo by a single point mutation in avirulent Brucellastrain, indicative of a transcriptional rewiring event. In additionto major domain organization differences existing between BtaEproteins within the genus Brucella,our analyses revealed that sequences upstream of btaEdisplay high variability probably associated to intrinsic promoterstructural features, which may serve as a substrate for reciprocalselection during co-evolution between this pathogen and its mammalianhost.