Abstract
Brucellosis, also known as “undulant fever” is a zoonotic disease caused by Brucella, which is a facultative intracellular bacterium. Despite efforts to eradicate this disease, infection in uncontrolled domestic animals persists in several countries and therefore transmission to humans is common. Brucella evasion of the innate immune system depends on its ability to evade the mechanisms of intracellular death in phagocytic cells. The BvrR-BvrS two-component system allows the bacterium to detect adverse conditions in the environment. The BvrS protein has been associated with genes of virulence factors, metabolism, and membrane transport. In this study, we predicted the DNA sequence recognized by BvrR with Gibbs Recursive Sampling and identified the three-dimensional structure of BvrR using I-TASSER suite, and the interaction mechanism between BvrR and DNA with Protein-DNA docking and molecular dynamics (MD) simulation. Based on the Gibbs recursive Sampling analysis, we found the motif AAHTGC (H represents A, C, and T nucleotides) as a possible sequence recognized by BvrR. The docking and EMD simulation results showed that C-terminal effector domain of BvrR protein is likely to interact with AAHTGC sequence. In conclusion, we predicted the structure, recognition motif, and interaction of BvrR with DNA.
Highlights
Brucellosis is one of the most common zoonoses in the world and is caused by microorganisms of the genus Brucella, which can be transmitted directly or indirectly to humans
The N-terminal receiver domain has high homology with protein PmrA (3W9SB) and a signal transduction histidine kinase (3C97A). This domain belongs to the Superfamily 3.40.50.2300 and is the one that interacts with the sensor BvrS, which correlates with its protein binding activity and phosphorelay signal transduction activities. All these results, including the ones obtained with VERIFY3D, ERRAT and ProSA that prove the accuracy of the model, validate the BvrR structural model, even though some small regions were modeled in an unusual way
This may be because the modeling template contained those variations, which were transferred to the model; it may be due to the lack of better templates on which to base the prediction of the BvrR structure
Summary
Brucellosis is one of the most common zoonoses in the world and is caused by microorganisms of the genus Brucella, which can be transmitted directly or indirectly to humans. The disease is transmitted from animals to humans through genital excretions and contaminated milk, the greatest source of human infection [1,2]. Infections by B. abortus and B. suis usually affect occupational groups (veterinarians, farmers, and abattoir workers), whereas that caused by B. melitensis is more frequent in the community [5,6]. Acute brucellosis manifests as a febrile disease. Brucellosis without treatment progresses to a disabling chronic disease with severe complications, such as central nervous system (CNS) affectations, osteomyelitis, keratitis, Molecules 2019, 24, 3137; doi:10.3390/molecules24173137 www.mdpi.com/journal/molecules
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