The BMEI0216 gene of Brucella melitensis is required for internalization in HeLa cells

Hernández‐Castro, Rigoberto; Verdugo-Rodríguez, Antonio; Puente, José L.; Suárez-Güemes, Francisco

doi:10.1016/j.micpath.2007.08.008

Cited by 33 publications

(32 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The roles of type IV secretion system (T4SS) in Brucella invasion have been investigated and it is generally accepted that the T4SS is not involved [13]. More recent study showed that BMEI0216 gene of B. melitensis is required for internalization in HeLa cells [14]. Essential genes encoding invasins and adhesins have been identified by Brucella genome analysis, but those molecules have not been investigated on Brucella surface [15].…”

Section: Introductionmentioning

confidence: 99%

Evidence of Brucella abortus OPS dictating uptake and restricting NF-κB activation in murine macrophages

Pei

Turse

Ficht

2008

Microbes and Infection

View full text Add to dashboard Cite

Smooth Brucella abortus S2308 is virulent while rough derivatives are attenuated. Intracellular killing is often blamed for these differences. In the studies described, uptake kinetics and interaction of S2308 and S2308 manBA::Tn5 (CA180) rough mutants with macrophages were investigated. The results revealed that smooth B. abortus was rapidly internalized, achieving a maximum level in less than 5 minutes without additional uptake over the next 30 minutes. In contrast, continued uptake of the rough mutant was observed and only achieves a maximum level after 30 minutes. The results were confirmed by the differences in F-actin polymerization, lipid raft staining, early endosome colocalization and electron microscopic observations after smooth and rough Brucella infection. We also demonstrated for the first time that uptake of S2308, but not rough mutant CA180 was PI3-kinase and toll-like receptor 4 (TLR4) dependent. Differences in uptake were associated with differences in macrophage activation with regard to NF-κB translocation and cytokine production. These results provide evidence that the presence of B. abortus OPS dictates the interactions between Brucella and specific cell surface receptors minimizing macrophage activation and enhancing Brucella survival and/or persistence.

show abstract

Section: Introductionmentioning

confidence: 99%

Evidence of Brucella abortus OPS dictating uptake and restricting NF-κB activation in murine macrophages

Pei

Turse

Ficht

2008

Microbes and Infection

View full text Add to dashboard Cite

show abstract

“…Several bacterial filamentous or nonpolymeric adhesins have been shown to participate in the primary interaction with the host cells as well as with components of the extracellular matrix (ECM) (11). Cumulative evidence supports the idea that adhesion to the ECM or to host cells is also an important step for Brucella infection (12)(13)(14)(15)(16). It was proposed that binding of Brucella to the host is mediated by host molecules containing sialic acid and/or sulfated residues and by components of the ECM such as fibronectin, collagen, and vitronectin.…”

mentioning

confidence: 98%

BtaE, an Adhesin That Belongs to the Trimeric Autotransporter Family, Is Required for Full Virulence and Defines a Specific Adhesive Pole of Brucella suis

et al. 2013

View full text Add to dashboard Cite

dBrucella is responsible for brucellosis, one of the most common zoonoses worldwide that causes important economic losses in several countries. Increasing evidence indicates that adhesion of Brucella spp. to host cells is an important step to establish infection. We have previously shown that the BmaC unipolar monomeric autotransporter mediates the binding of Brucella suis to host cells through cell-associated fibronectin. Our genome analysis shows that the B. suis genome encodes several additional potential adhesins. In this work, we characterized a predicted trimeric autotransporter that we named BtaE. By expressing btaE in a nonadherent Escherichia coli strain and by phenotypic characterization of a B. suis ⌬btaE mutant, we showed that BtaE is involved in the binding of B. suis to hyaluronic acid. The B. suis ⌬btaE mutant exhibited a reduction in the adhesion to HeLa and A549 epithelial cells compared with the wild-type strain, and it was outcompeted by the wild-type strain in the binding to HeLa cells. The knockout btaE mutant showed an attenuated phenotype in the mouse model, indicating that BtaE is required for full virulence. BtaE was immunodetected on the bacterial surface at one cell pole. Using old and new pole markers, we observed that both the BmaC and BtaE adhesins are consistently associated with the new cell pole, suggesting that, in Brucella, the new pole is functionally differentiated for adhesion. This is consistent with the inherent polarization of this bacterium, and its role in the invasion process.

show abstract

“…We believe that systematic modification of these other functions, in conjunction with tuf2 mutants of M28, and host-response studies will together provide a comprehensive account of the attenuation of the M5-90 vaccine strain. A systematic review of the literature by Crasta et al (17) tabulated 236 potential virulence factors and an additional 53 genes previously implicated in Brucella virulence (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38). Of these 289 potential virulence factors, only BM28_A0655 (encoding a soluble lytic murein transglycosylase), which is involved in amino sugar metabolism and N-glycan biosynthesis, showed consistent differences between M5-90 and the three virulent strains (28).…”

Section: Discussionmentioning

confidence: 99%

Comparison of Genomes of Brucella melitensis M28 and the B. melitensis M5-90 Derivative Vaccine Strain Highlights the Translation Elongation Factor Tu Gene tuf2 as an Attenuation-Related Gene

Wang

Qiao

et al. 2013

Infect Immun

View full text Add to dashboard Cite

c Brucella melitensis causes brucellosis, a disease affecting sheep, cattle, and sometimes humans. Attenuated B. melitensis strain M5-90, derived from virulent strain M28, is widely used as a live vaccine in ruminants in China. Genetic differences between the strains may cast light on the mechanism of attenuation. We recently reported the complete genomic sequences of M28 and M5-90. Genome organization is highly conserved between these isolates, and also with virulent strains 16 M and ATCC 23457. Analysis revealed 23 open reading frames (ORFs) with consistent differences between M5-90 and the virulent strains. Notably, the tuf2 gene encoding translation elongation factor EF-Tu from M5-90 contained 50 single nucleotide polymorphisms (SNPs) and 9 gaps (indels) compared to tuf2 of M28 or of the other virulent strains. There were no changes in tuf1. To evaluate the potential role of EF-Tu in pathogenesis, tuf1 and tuf2 mutants of M28 and an M5-90 strain harboring wild-type tuf2 were constructed, and their virulence/attenuation was evaluated in vivo. We report that the tuf2 gene plays an important role in the attenuation of M5-90 virulence. Brucella melitensis, the first species in the genus Brucella to be described, causes abortion in goats and sheep and Malta fever in humans. Currently, there are nine recognized species of the bacterium Brucella, based on host preferences and phenotypic differences (1). The six classically recognized species of this facultative intracellular parasite are B. melitensis (sheep and goats), B. abortus (cattle), B. suis (pigs, reindeer, and hares), B. canis (dogs), B. ovis (sheep), and B. neotomae (desert wood rats) (2). In humans, B. melitensis is the most highly pathogenic, and infection typically takes place via the consumption of unpasteurized milk and milk products. Attenuated B. melitensis M5-90, derived from virulent strain M28, is widely used as a live vaccine in sheep, goats, and cattle in China (3, 4). However, such strains retain pathogenicity for humans and to date no effective vaccine has been approved for human use. Because of its epidemic potential, the absence of a human vaccine, and the effectiveness of aerosol infection, this agent is classified as a biosafety level 3 pathogen and has been designated a potential bioterrorism agent (5).The genome of the first Brucella melitensis strain to be sequenced, 16 M, comprises ϳ3.3 Mb of unique sequence shared between two circular chromosomes: the larger chromosome (chromosome I) is ϳ2.1 Mb, whereas chromosome II is ϳ1.2 Mb. Eleven complete genome sequences representing six species of Brucella are currently available, and the genomes of several other Brucella strains/species are in the process of being sequenced (1).The different genomes are very similar in size and in the numbers of genes and proteins. Sequence comparisons have provided firm evidence of horizontal gene transfer between different Brucella species and strains, despite their predominantly intracellular lifestyle, and phylogenomic analysis of orthologous gene famil...

show abstract

The BMEI0216 gene of Brucella melitensis is required for internalization in HeLa cells

Cited by 33 publications

References 25 publications

Evidence of Brucella abortus OPS dictating uptake and restricting NF-κB activation in murine macrophages

Evidence of Brucella abortus OPS dictating uptake and restricting NF-κB activation in murine macrophages

BtaE, an Adhesin That Belongs to the Trimeric Autotransporter Family, Is Required for Full Virulence and Defines a Specific Adhesive Pole of Brucella suis

Comparison of Genomes of Brucella melitensis M28 and the B. melitensis M5-90 Derivative Vaccine Strain Highlights the Translation Elongation Factor Tu Gene tuf2 as an Attenuation-Related Gene

Contact Info

Product

Resources

About