Deletion of the LuxR-type regulator VjbR in Brucella canis affects expression of type IV secretion system and bacterial virulence, and the mutant strain confers protection against Brucella canis challenge in mice

2020 ◽  
Vol 139 ◽  
pp. 103865 ◽  
Author(s):  
Yufu Liu ◽  
Jiali Sun ◽  
Xiaowei Peng ◽  
Hao Dong ◽  
Yuming Qin ◽  
...  
2010 ◽  
Vol 79 (3) ◽  
pp. 1033-1043 ◽  
Author(s):  
Athanasios Paschos ◽  
Andreas den Hartigh ◽  
Mark A. Smith ◽  
Vidya L. Atluri ◽  
Durga Sivanesan ◽  
...  

ABSTRACTAs bacterial pathogens develop resistance against most currently used antibiotics, novel alternatives for treatment of microbial infectious diseases are urgently needed. Targeting bacterial virulence functions in order to disarm pathogens represents a promising alternative to classical antibiotic therapy. Type IV secretion systems, which are multiprotein complexes in the cell envelope that translocate effectors into host cells, are critical bacterial virulence factors in many pathogens and excellent targets for such “antivirulence” drugs. The VirB8 protein from the mammalian pathogenBrucellawas chosen as a specific target, since it is an essential type IV secretion system component, it participates in multiple protein-protein interactions, and it is essential for the assembly of this translocation machinery. The bacterial two-hybrid system was adapted to assay VirB8 interactions, and a high-throughput screen identified specific small-molecule inhibitors. VirB8 interaction inhibitors also reduced the levels of VirB8 and of other VirB proteins, and many of them inhibitedvirBgene transcription inBrucella abortus2308, suggesting that targeting of the secretion system has complex regulatory effectsin vivo. One compound strongly inhibited the intracellular proliferation ofB. abortus2308 in a J774 macrophage infection model. The results presented here show thatin vivoscreens with the bacterial two-hybrid assay are suited to the identification of inhibitors ofBrucellatype IV secretion system function.


2013 ◽  
Vol 163 (1-2) ◽  
pp. 196-199 ◽  
Author(s):  
Juan Jacobo de la Cuesta-Zuluaga ◽  
Miryan Margot Sánchez-Jiménez ◽  
Juliana Martínez-Garro ◽  
Martha Olivera-Angel

Author(s):  
XiaoYu Deng ◽  
Jinke He ◽  
Yueli Wang ◽  
Qin Yang ◽  
Ji Hai Yi ◽  
...  

Brucella abortus is a Gram-negative intracellular parasite bacteria causing serious health hazards in humans and animals. The type IV secretion system (T4SS), encoded by the virB promoter, has been identified as an important virulence factor for Brucella abortus, but the impact on Brucella abortus A19 remains unclear. In this study, the T4SS of Brucella abortus A19 was inactivated by deleting the virB promoter, resulting in a mutant strain A19ΔvirB. Real-time PCR and Western-blotting analysis demonstrated that T4SS-related proteins were not expressed after virB promoter deletion. Moreover, the survival rate of A19 in high salt and strong acidic environments was decreased after virB promoter deletion. Compared to the parental strain A19, the A19ΔvirB mutant strain showed reduced growth rate in TSB, decreased invasion ability to macrophages and dendritic cells, and reduced virulence of the mutant strain in macrophages, dendritic cells and mice. In addition, the A19ΔvirB mutant strain showed enhanced autophagy on macrophages and dendritic cells compared with A19, and the A19ΔvirB mutant strain was able to upregulate IL-6 and downregulate IL-10 in macrophages. These data help us to better understand the T4SS of the A19 vaccine strain and contribute to our efforts to improve Brucella vaccines.


2001 ◽  
Vol 120 (5) ◽  
pp. A652-A653
Author(s):  
Y HIRATA ◽  
S MAEDA ◽  
Y MITUNO ◽  
M AKANUMA ◽  
T KAWABE ◽  
...  

2019 ◽  
Vol 156 (6) ◽  
pp. S-171-S-172 ◽  
Author(s):  
Lydia Wroblewski ◽  
Eunyoung Choi ◽  
Christine Petersen ◽  
Alberto Delgado ◽  
M. Blanca Piazuelo ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document