Outer Membrane Vesicles From Brucella melitensis Modulate Immune Response and Induce Cytoskeleton Rearrangement in Peripheral Blood Mononuclear Cells

Ávila-Calderón, Eric Daniel; Medina-Chávez, Olín; Flores‐Romo, Leopoldo; Donis-Maturano, Luis; López-Merino, Ahidé; Arellano-Reynoso, Beatriz; Aguilera‐Arreola, Ma. Guadalupe; Ruíz, Enrico A.; Gómez-Lunar, Zulema; Witonsky, Sharon G.; Contreras-Rodríguez, Araceli

doi:10.3389/fmicb.2020.556795

Cited by 7 publications

(4 citation statements)

References 60 publications

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“…MiR-744 is known to be associated with the innate immunity pathway and acts as a tumor suppressor, thereby inhibiting cell proliferation and promoting cell apoptosis ( Pilson et al, 2020 ; Yuan et al, 2020 ). Meanwhile, the cytokine encoded genes, including IL-6 , IL-7 , IL-11 , IL-23A and IL-24 , were significantly changed in our RNA-seq data, which were partially consistent with previous studies ( Avila-Calderón et al, 2020 ; Zhou et al, 2021 ). IL-6 is a pleiotropic, pro-inflammatory cytokine produced by a variety of cell types, including lymphocytes, monocytes, and fibroblasts.…”

Section: Discussionsupporting

confidence: 92%

Integrated mRNA-seq and miRNA-seq analysis of goat fibroblasts response to Brucella Melitensis strain M5-90

Li¹,

Chen²,

Wang³

et al. 2021

PeerJ

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Brucellosis is a globally zoonotic bacterial disease of humans and various animals including goats, sheep, and cattle. Brucella melitensis M5-90, a live attenuated vaccine strain, has been widely used to prevent brucellosis in goats and sheep. However, the molecular mechanisms governing protective immunity response in non-professional phagocytes infected with B. melitensis M5-90 have not been fully investigated, especially in goats. In our research, goat fibroblasts were used as in vitro models to determine these mechanisms by transcriptome analysis. After incubating with B. melitensis M5-90 3 h, the infected goat fibroblasts were collected at 0 h, 4 h, 24 h, 48 h and 72 h for RNA-seq. The results indicated that there were totally 11,819 differentially expressed genes (DEGs) and 777 differentially expressed (DE) miRNAs found in experiment groups compared with the control groups (|log2(Foldchange)|≥1, FDR<0.05). GO and KEGG enrichment analyses revealed that down-regulated genes were involved in the riboflavin metabolism and positive regulation of IL-8 secretion pathway. The up-regulated genes were mainly involved in adaptive immunity, including TNF signaling pathway, MAPK signaling pathway and JAK/STAT pathway. Additionally, cytokine-cytokine receptor interaction, natural killer cell mediated cytotoxicity and toll-like receptor signaling pathway, which associated with innate immunity pathways, were also induced. Based on the Pearson correlation coefficients and prediction results of TargetScan and miRanda, the miRNA-mRNA networks of NFKB1, IFNAR2 and IL10RB were constructed and verified in goat fibroblasts by qPCR, which demonstrated that goat fibroblasts displayed immunomodulatory properties. Our findings provide a deeper insight into the host miRNA-driven B. melitensis defense mechanism and reveal the transcriptome changes involved in the innate and adaptive immune response of the goats to B. melitensis infection.

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Section: Discussionsupporting

confidence: 92%

Integrated mRNA-seq and miRNA-seq analysis of goat fibroblasts response to Brucella Melitensis strain M5-90

Li¹,

Chen²,

Wang³

et al. 2021

PeerJ

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“…These missing genes may have impacted the virulence of the ancient strain. Several of these genes were involved in the Brucella virulence related regulatory and sensory (BvrR/BvrS) mechanism responsible for directing the expression of several outer membrane proteins [ 53 , 54 ]. The same results were also found with a [ 55 ] database search ( S1 File ).…”

Section: Resultsmentioning

confidence: 99%

A 14th century CE Brucella melitensis genome and the recent expansion of the Western Mediterranean clade

Long,

Hider,

Duggan

et al. 2023

PLoS Pathog

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Brucellosis is a disease caused by the bacterium Brucella and typically transmitted through contact with infected ruminants. It is one of the most common chronic zoonotic diseases and of particular interest to public health agencies. Despite its well-known transmission history and characteristic symptoms, we lack a more complete understanding of the evolutionary history of its best-known species—Brucella melitensis. To address this knowledge gap we fortuitously found, sequenced and assembled a high-quality ancient B. melitensis draft genome from the kidney stone of a 14th-century Italian friar. The ancient strain contained fewer core genes than modern B. melitensis isolates, carried a complete complement of virulence genes, and did not contain any indication of significant antimicrobial resistances. The ancient B. melitensis genome fell as a basal sister lineage to a subgroup of B. melitensis strains within the Western Mediterranean phylogenetic group, with a short branch length indicative of its earlier sampling time, along with a similar gene content. By calibrating the molecular clock we suggest that the speciation event between B. melitensis and B. abortus is contemporaneous with the estimated time frame for the domestication of both sheep and goats. These results confirm the existence of the Western Mediterranean clade as a separate group in the 14th CE and suggest that its divergence was due to human and ruminant co-migration.

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“…Other interesting structures promoting adhesiveness to solid surfaces in Brucella are the OM vesicles (OMVs), commonly called blebs (Godefroid et al, 2010). Blebs are nanovesicles released from the OM whose composition (Gamazo and Moriyón, 1987;Avila-Calderón et al, 2020;Ruiz-Palma et al, 2021) and amount (Solanki et al, 2021) have been associated with the lack of O-PS, and they are overproduced in strains that auto-agglutinate (Godefroid et al, 2010). As shown by TEM (Figure 3G), the mutants showed abundant OMVs as outward bulges protruding from the surface or as already detached vesicles, while the OM maintained its integrity.…”

Section: Blocking O-polysaccharide Transport Causes Pleiotropic Chang...mentioning

confidence: 99%

Brucella melitensis Wzm/Wzt System: Changes in the Bacterial Envelope Lead to Improved Rev1Δwzm Vaccine Properties

et al. 2022

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The lipopolysaccharide (LPS) O-polysaccharide (O-PS) is the main virulence factor in Brucella. After synthesis in the cytoplasmic membrane, O-PS is exported to the periplasm by the Wzm/Wzt system, where it is assembled into a LPS. This translocation also engages a bactoprenol carrier required for further biosynthesis pathways, such as cell wall biogenesis. Targeting O-PS export by blockage holds great potential for vaccine development, but little is known about the biological implications of each Wzm/Wzt moiety. To improve this knowledge and to elucidate its potential application as a vaccine, we constructed and studied wzm/wzt single- and double-deletion mutants, using the attenuated strain Brucella melitensis Rev1 as the parental strain. This allowed us to describe the composition of Brucella peptidoglycan for the first time. We observed that these mutants lack external O-PS yet trigger changes in genetic transcription and in phenotypic properties associated with the outer membrane and cell wall. Both mutants are highly attenuated; unexpectedly, Rev1Δwzm also excels as an immunogenic and effective vaccine against B. melitensis and Brucella ovis in mice, revealing that low persistence is not at odds with efficacy. Rev1Δwzm is attenuated in BeWo trophoblasts, does not infect mouse placentas, and is safe in pregnant ewes. Overall, these attributes and the minimal serological interference induced in sheep make Rev1Δwzm a highly promising vaccine candidate.

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Outer Membrane Vesicles From Brucella melitensis Modulate Immune Response and Induce Cytoskeleton Rearrangement in Peripheral Blood Mononuclear Cells

Cited by 7 publications

References 60 publications

Integrated mRNA-seq and miRNA-seq analysis of goat fibroblasts response to Brucella Melitensis strain M5-90

Integrated mRNA-seq and miRNA-seq analysis of goat fibroblasts response to Brucella Melitensis strain M5-90

A 14th century CE Brucella melitensis genome and the recent expansion of the Western Mediterranean clade

Brucella melitensis Wzm/Wzt System: Changes in the Bacterial Envelope Lead to Improved Rev1Δwzm Vaccine Properties

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