Brucella abortus BspJ Is a Nucleomodulin That Inhibits Macrophage Apoptosis and Promotes Intracellular Survival of Brucella

Abstract

To date, a variety of Brucella effector proteins have been found to mediate host cell secretion, autophagy, inflammation, and other signal pathways, but nuclear effector proteins have not yet been reported. We identified the first Brucella nucleomodulin, BspJ, and we screened out the BspJ interaction host proteins NME/NM23 nucleoside diphosphate kinase 2 (NME2) and creatine kinase B (CKB) through yeast two-hybrid and co-immunoprecipitation assays. These proteins are related to the host cell energy synthesis, metabolism, and apoptosis pathways. Brucella nucleomodulin BspJ will decrease the expression level of NME2 and CKB. In addition, BspJ gene deletion strains promoted the apoptosis of macrophages and reduced the intracellular survival of Brucella in host cells. In short, we found nucleomodulin BspJ may directly or indirectly regulate host cell apoptosis through the interaction with NME2 and CKB by mediating energy metabolism pathways in response to the intracellular circulation of Brucella infection, but the mechanism needs further study.

Doxycycline Induces Apoptosis of Brucella Suis S2 Strain-Infected HMC3 Microglial Cells by Activating Calreticulin-Dependent JNK/p53 Signaling Pathway

“…Compared with the control group, the p-JNK and p-p53 protein levels in the 8 h group were significantly increased ( Figures 1C–E ). Because Brucella has been reported to inhibit apoptosis in macrophages ( Ahmed et al., 2016 ; Ma et al., 2020 ), we examined apoptosis in B. suis S2-infected HMC3 cells at different timepoints by flow cytometry ( Figure 1G ). Flow cytometric analysis indicated that compared with the control group, the apoptosis rate in HMC3 cells was reduced in the 2 h group but was increased in the 8 h group ( Figure 1F ).…”

“…Brucella is able to escape the killing action of professional phagocytes by replicating diffusely within the endoplasmic reticulum of macrophages ( Ma et al., 2020 ). As a multifunctional protein in the endoplasmic reticulum, CALR plays a role in anti-apoptosis through regulating calcium ion concentration ( Gold et al., 2010 ).…”

“…As recent study has shown that another intracellular bacterium, Coxiella burnetii , survives and replicates within host cells by suppressing apoptosis; as in our study, Dox limits C. burnetii survival by inducing apoptosis ( Hume et al., 2018 ), but the specific mechanism of this effect is still unclear. Brucella is also an intracellular bacterium that inhibits cell apoptosis to survive and proliferate ( Scian et al., 2013 ; Ma et al., 2020 ). In the present study, we have demonstrated the mechanism of apoptosis inhibition by B. suis S2 as well as the mechanism of Dox induced-apoptosis in HMC3 cells.…”

Mucosal Vaccination Primes NK Cell-Dependent Development of CD8+ T Cells Against Pulmonary Brucella Infection

“…It has been reported that lung resident macrophages provide a replicative niche for wt Brucella strains ( 42 ). Within alveolar macrophages, Brucella inhibits host cell apoptosis, evades immune surveillance which in turn makes more difficult for antigen processing and presentation ( 53 , 54 ). In addition, during pulmonary infection with wt Brucella , alveolar macrophages inhibit pulmonary DC activation.…”

The Recombinant Expression Proteins FnBP and ClfA From Staphylococcus aureus in Addition to GapC and Sip From Streptococcus agalactiae Can Protect BALB/c Mice From Bacterial Infection

“…After the target genes were optimized, we commissioned GENERAL BIOL (Anhui, China) to synthesize the sequences and constructed each tandem sequence (FC, GS, and FCGS) by ligation into the vector pET28a/pET32a (EMD Biosciences, Novagen, San Diego, CA, USA). The Phyre2 software program ( http://www.sbg.bio.ic.ac.uk/phyre2/html/page.cgi?id=index ) was used to predict the tertiary structures of the recombinant fusion proteins ( 26 ).…”