title: Intracellularly induced cyclophilins play an important role in stress adaptation and virulence of Brucella abortus.
abstract: Brucella is an intracellular bacterial pathogen that causes the worldwide zoonotic disease brucellosis. Brucella virulence relies on its ability to transition to an intracellular lifestyle within host cells. Thus, this pathogen must sense its intracellular localization and then reprogram gene expression for survival within the host cell. A comparative proteomic investigation was performed to identify differentially expressed proteins potentially relevant for Brucella intracellular adaptation. Two proteins identified as cyclophilins (CypA and CypB) were overexpressed in the intracellular environment of the host cell in comparison to laboratory-grown Brucella. To define the potential role of cyclophilins in Brucella virulence, a double-deletion mutant was constructed and its resulting phenotype was characterized. The Brucella abortus ΔcypAB mutant displayed increased sensitivity to environmental stressors, such as oxidative stress, pH, and detergents. In addition, the B. abortus ΔcypAB mutant strain had a reduced growth rate at lower temperature, a phenotype associated with defective expression of cyclophilins in other microorganisms. The B. abortus ΔcypAB mutant also displays reduced virulence in BALB/c mice and defective intracellular survival in HeLa cells. These findings suggest that cyclophilins are important for Brucella virulence and survival in the host cells.
authors.affiliation: Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina. mroset@iibintech.com.ar
authors.forename: Mara S
authors.initials: MS
authors.lastname: Roset
authors.forename: Lucía
authors.initials: L
authors.lastname: García Fernández
authors.forename: Vito G
authors.initials: VG
authors.lastname: DelVecchio
authors.forename: Gabriel
authors.initials: G
authors.lastname: Briones
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002003:Brucella abortus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology*; D002006:Brucellosis / Q000235:genetics / Q000378:metabolism / Q000382:microbiology*; D045744:Cell Line, Tumor; D021983:Cyclophilins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation / Q000235:genetics; D040901:Proteomics / Q000379:methods; D013312:Stress, Physiological / Q000235:genetics / Q000502:physiology*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D021983:Cyclophilins