Cyclophilins play an important role in the stress adaptation and virulence of Brucella abortus

GARCÍA FERNANDEZ L.; COMERCI D. J.; ROSET M. S.

Puerto Madryn

Congreso; XLVI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular SAIB; 2010

Sociedad Argentina de Investigaciones Bioquímica y Biología Molecular

Brucella is a facultative intracellular pathogen that causes brucellosis, a worldwide zoonosis that affects a wide range of mammals and humans. Virulence of this pathogen is associated with the ability to survive and replicate within professional and non professional phagocytes. We performed a comparative intracellular proteomic experiment to identify genes that were differentially expressed during intracellular life of B. abortus. The observation of up-regulation of two cyclophilins during B. abortus intracellular life prompted us to speculate about their potential significant role during the infection. To provide a framework in order to answer this question, we constructed a double mutant of BAB1_1117 and BAB1_1118 genes by in frame deletion and characterized it. The B. abortus ppiase mutant was impaired in the ability to grow at low temperature and showed an increased sensitivity to several detergents, to oxidative stress and low pH conditions. In addition, the mutant displays a reduced virulence in BALB/c mice and defective intracellular replication in HeLa cells. All defects were reverted to the wild type phenotype by ectopic expression of wild type copy of the genes. These findings suggest that these genes products make an important contribution to Brucella pathogenesis, probably by allowing B. abortus to adapt to the harsh environment encountered within the hosts.is a facultative intracellular pathogen that causes brucellosis, a worldwide zoonosis that affects a wide range of mammals and humans. Virulence of this pathogen is associated with the ability to survive and replicate within professional and non professional phagocytes. We performed a comparative intracellular proteomic experiment to identify genes that were differentially expressed during intracellular life of B. abortus. The observation of up-regulation of two cyclophilins during B. abortus intracellular life prompted us to speculate about their potential significant role during the infection. To provide a framework in order to answer this question, we constructed a double mutant of BAB1_1117 and BAB1_1118 genes by in frame deletion and characterized it. The B. abortus ppiase mutant was impaired in the ability to grow at low temperature and showed an increased sensitivity to several detergents, to oxidative stress and low pH conditions. In addition, the mutant displays a reduced virulence in BALB/c mice and defective intracellular replication in HeLa cells. All defects were reverted to the wild type phenotype by ectopic expression of wild type copy of the genes. These findings suggest that these genes products make an important contribution to Brucella pathogenesis, probably by allowing B. abortus to adapt to the harsh environment encountered within the hosts.