title: The Brucella abortus general stress response system regulates chronic mammalian infection and is controlled by phosphorylation and proteolysis.
abstract: BACKGROUND
  Virulence of pathogenic bacteria is often determined by their ability to adapt to stress.
  
  
  RESULTS
  The Brucella abortus general stress response (GSR) system is required for chronic mammalian infection and is regulated by phosphorylation and proteolysis.
  
  
  CONCLUSIONS
  The B. abortus GSR signaling pathway has multiple layers of post-translational control and is a determinant of chronic infection.
  
  
  CONCLUSIONS
  This study provides new, molecular level insight into chronic Brucella infection. Brucella spp. are adept at establishing a chronic infection in mammals. We demonstrate that core components of the α-proteobacterial general stress response (GSR) system, PhyR and σ(E1), are required for Brucella abortus stress survival in vitro and maintenance of chronic murine infection in vivo. ΔphyR and ΔrpoE1 null mutants exhibit decreased survival under acute oxidative and acid stress but are not defective in infection of primary murine macrophages or in initial colonization of BALB/c mouse spleens. However, ΔphyR and ΔrpoE1 mutants are attenuated in spleens beginning 1 month postinfection. Thus, the B. abortus GSR system is dispensable for colonization but is required to maintain chronic infection. A genome-scale analysis of the B. abortus GSR regulon identified stress response genes previously linked to virulence and genes that affect immunomodulatory components of the cell envelope. These data support a model in which the GSR system affects both stress survival and the interface between B. abortus and the host immune system. We further demonstrate that PhyR proteolysis is a unique feature of GSR control in B. abortus. Proteolysis of PhyR provides a mechanism to avoid spurious PhyR protein interactions that inappropriately activate GSR-dependent transcription. We conclude that the B. abortus GSR system regulates acute stress adaptation and long term survival within a mammalian host and that PhyR proteolysis is a novel regulatory feature in B. abortus that ensures proper control of GSR transcription.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Hye-Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Clayton C
authors.initials: CC
authors.lastname: Caswell
authors.forename: Robert
authors.initials: R
authors.lastname: Foreman
authors.forename: R Martin
authors.initials: RM
authors.lastname: Roop
authors.forename: Sean
authors.initials: S
authors.lastname: Crosson
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D002003:Brucella abortus / Q000235:genetics* / Q000502:physiology; D002006:Brucellosis / Q000382:microbiology*; D002908:Chronic Disease; D017124:Conserved Sequence; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D056426:Genetic Loci; D054884:Host-Pathogen Interactions; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D018384:Oxidative Stress; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D013312:Stress, Physiological; D059467:Transcriptome
chemical_list: D001426:Bacterial Proteins
keywords: Bacterial Pathogenesis; Bacterial Signal Transduction; Bacterial Transcription; Brucella; General Stress Response; Infectious Diseases; PhyR; Stress Response
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