title: Dual input control: activation of the Bartonella henselae VirB/D4 type IV secretion system by the stringent sigma factor RpoH1 and the BatR/BatS two-component system.
abstract: The co-ordinated expression of virulence factors is a critical process for any bacterial pathogen to colonize its host. Here we investigated the mechanisms of niche adaptation of the zoonotic pathogen Bartonella henselae by combining genetic approaches and shotgun proteomics. We demonstrated that expression of the VirB/D4 type IV secretion system (T4SS) and its secreted effector proteins require the alternative sigma factor RpoH1, which levels are controlled by the stringent response (SR) components DksA and SpoT. The RpoH1-dependent activation requires an active BatR/BatS two-component system (TCS) while BatR expression is controlled by RpoH1 and the SR components. Deletion of spoT results in a strong attenuation of VirB/D4 T4SS expression whereas dksA, rpoH1 or batR deletion fully abolishes its activity. In contrast to their activating effect on the VirB/D4 T4SS, which is critical at the early stage of host infection, SpoT and DksA negatively regulate the Trw T4SS, which mediates host-specific erythrocyte infection at a later stage of the colonization process. Our findings support a model where the SR signalling and the physiological pH-induced BatR/BatS TCS conjointly control the spatiotemporal expression of B. henselae adaptation factors during host infection.
authors.affiliation: Focal Area Infection Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, 4056, Basel, Switzerland.
authors.forename: Maxime
authors.initials: M
authors.lastname: Québatte
authors.forename: Mathias S
authors.initials: MS
authors.lastname: Dick
authors.forename: Volkhard
authors.initials: V
authors.lastname: Kaever
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmidt
authors.forename: Christoph
authors.initials: C
authors.lastname: Dehio
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D058947:Bacterial Secretion Systems; D018416:Bartonella henselae / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D015964:Gene Expression Regulation, Bacterial; D054884:Host-Pathogen Interactions; D016296:Mutagenesis; D040901:Proteomics; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D012808:Sigma Factor; D037521:Virulence Factors