Abstract
Brucella Cu-Zn superoxide dismutase (Cu-Zn SOD) is a periplasmic protein, and immunization of mice with recombinant Cu-Zn SOD protein confers protection against Brucella abortus infection. However, the role of Cu-Zn SOD during the process of Brucella infection remains unknown. Here, we report that Cu-Zn SOD is secreted into culture medium and is translocated into host cells independent of type IV secretion systems (T4SS). Furthermore, co-immunoprecipitation and immunofluorescence studies reveal that Brucella abortus Cu-Zn SOD interacts with the small GTPase Sar1. Overexpression of Cu-Zn SOD in Brucella abortus inhibits bacterial intracellular growth by abolishing Sar1 activity in a manner independent of reactive oxygen species (ROS) production.
Highlights
The genus Brucella is a gram-negative facultative intracellular pathogen that causes brucellosis in humans and many animals, including cows, goats, sheep, dogs, pigs and et al Brucellosis is one of the zoonotic diseases, which causes abortion and sterility in animals, and debilitating disorders in humans
We show that the periplasmic protein Cu-Zn SOD in B. abortus is secreted into culture medium and is able to be translocated into host cells in T4SS VirB-independent manner
We discovered a novel role for SOD in this process whereby overexpressed-Cu-Zn SOD can bind to the small GTPase protein Sar1, leading to inactivity of Sar1 and inhibition of bacterial intracellular growth
Summary
The genus Brucella is a gram-negative facultative intracellular pathogen that causes brucellosis in humans and many animals, including cows, goats, sheep, dogs, pigs and et al Brucellosis is one of the zoonotic diseases, which causes abortion and sterility in animals, and debilitating disorders in humans. Better understanding of the Brucella proteins that support Brucella intracellular growth is critical to design a safe and effective brucellosis vaccine [1]. The Brucella Cu-Zn superoxide dismuatse (CuZn SOD) is an 18.5 KD periplasmic protein encoded by Brucella sodC gene, and an appropriate immune response to this protein confers protection against B. abortus challenge in a mouse model [2]. Overexpression of CuZn SOD in a RB51 vaccine strain (RB51SOD strain) significantly increases its vaccine efficacy against B. abortus challenge and decreases its survival rate in macrophages [4]. As the virulence of Brucella depends on survival and replication properties in host cells [1], it will be important to determine the role of CuZn SOD in regulating Brucella intracellular growth for designing a safe vaccine in the future
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