Brucella T4SS: the VIP pass inside host cells

Lacerda, Thaís Lourdes Santos; Salcedo, Suzana P.; Gorvel, Jean‐Pierre

doi:10.1016/j.mib.2012.11.005

Cited by 43 publications

(41 citation statements)

References 57 publications

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“…Three species, Brucella abortus, B. melitensis, and B. suis, are the most common causes of brucellosis in domestic livestock and humans. These brucellae can grow both in vitro and within host cells, and their pathogenicity results largely from their capacity to escape prompt detection by innate immunity and the use of a type IV secretion system to reach the replicative niche, an endoplasmic reticulum-derived vacuole (1)(2)(3)(4)(5)(6). In this compartment, these bacteria multiply extensively, which shows their ability to efficiently use substrates provided by the host.…”

mentioning

confidence: 99%

Brucella abortus Depends on Pyruvate Phosphate Dikinase and Malic Enzyme but Not on Fbp and GlpX Fructose-1,6-Bisphosphatases for Full Virulence in Laboratory Models

et al. 2014

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The brucellae are the etiological agents of brucellosis, a worldwide-distributed zoonosis. These bacteria are facultative intracellular parasites and thus are able to adjust their metabolism to the extra-and intracellular environments encountered during an infectious cycle. However, this aspect of Brucella biology is imperfectly understood, and the nutrients available in the intracellular niche are unknown. Here, we investigated the central pathways of C metabolism used by Brucella abortus by deleting the putative fructose-1,6-bisphosphatase (fbp and glpX), phosphoenolpyruvate carboxykinase (pckA), pyruvate phosphate dikinase (ppdK), and malic enzyme (mae) genes. In gluconeogenic but not in rich media, growth of ⌬ppdK and ⌬mae mutants was severely impaired and growth of the double ⌬fbp-⌬glpX mutant was reduced. In macrophages, only the ⌬ppdK and ⌬mae mutants showed reduced multiplication, and studies with the ⌬ppdK mutant confirmed that it reached the replicative niche. Similarly, only the ⌬ppdK and ⌬mae mutants were attenuated in mice, the former being cleared by week 10 and the latter persisting longer than 12 weeks. We also investigated the glyoxylate cycle. Although aceA (isocitrate lyase) promoter activity was enhanced in rich medium, aceA disruption had no effect in vitro or on multiplication in macrophages or mouse spleens. The results suggest that B. abortus grows intracellularly using a limited supply of 6-C (and 5-C) sugars that is compensated by glutamate and possibly other amino acids entering the Krebs cycle without a critical role of the glyoxylate shunt.

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confidence: 99%

Brucella abortus Depends on Pyruvate Phosphate Dikinase and Malic Enzyme but Not on Fbp and GlpX Fructose-1,6-Bisphosphatases for Full Virulence in Laboratory Models

et al. 2014

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“…Virulence in the zoonotic pathogen Brucella is completely dependent on the presence of the type IV secretion virB system that translocates several effectors to the host cell which modulate the intracellular fate of the BCV (27). The VirB complex in Brucella has a high degree of similarity to the VirB system in Agrobacterium, and because much has been done at the biochemical and structural level with this bacterium, most of what we know about the system in Brucella is due to extrapolation.…”

Section: Discussionmentioning

confidence: 99%

VirJ Is a Brucella Virulence Factor Involved in the Secretion of Type IV Secreted Substrates

Giudice¹,

Döhmer

Spera³

et al. 2016

Journal of Biological Chemistry

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The VirB secretion apparatus in Brucella belongs to the type IV secretion systems present in many pathogenic bacteria and is absolutely necessary for the efficient evasion of the Brucellacontaining vacuole from the phagocytic route in professional phagocytes. This system is responsible for the secretion of a plethora of effector proteins that alter the biology of the host cell and promote the intracellular replication process. Although many VirB substrates have been identified in Brucella, we still know very little about the secretion mechanism that mediates their translocation across the two membranes and the periplasmic space. In this manuscript, we describe the identification of a gene, virJ, that codes for a protein with periplasmic localization that is involved in the intracellular replication process and virulence in mice. Our analysis revealed that this protein is necessary for the secretion of at least two VirB substrates that have a periplasmic intermediate and that it directly interacts with them. We additionally show that VirJ also associates with the apparatus per se and that its absence affects the assembly of the complex. We hypothesize that VirJ is part of a secretion platform composed of the translocon and several secretion substrates and that it probably coordinates the proper assembly of this macromolecular complex.Intracellular pathogenic bacteria have the capacity to circumvent the host defenses to establish a secure niche for replication. The mechanisms necessary to establish this "safe haven" are multiple, but in many cases they depend on the capacity of the bacteria to secrete and translocate effector molecules to the host cell (1). Brucella spp., the causative agent of brucellosis, is a zoonotic Gram-negative bacterium that still inflicts important economic losses in livestock and serious human health problems in endemic areas (2). Brucella is an intracellular pathogen with the capacity to avoid the bactericidal effects of its target cells, such as macrophages (one of the primary cell targets). To achieve this, the bacterium codes for a T4SS 5 that secretes and translocates effector proteins to the host cell that modulate the cellular response, avoiding the phagocytic process and favoring the infectious process (3-10). In Brucella, this secretion system is named virB because of its homology to the Agrobacterium tumefaciens conjugation-like system that translocates the T-DNA (transferred DNA) into the plant cell (11). The activity of the VirB system is necessary, in a first phase, to avoid the fusion of the BCV with the lysosomes and, in a second phase, to redirect its fate to an endoplasmic reticulum-derived membrane niche, where it actively replicates (3, 12).Type IV secretion systems are macromolecular complexes that span the inner membrane, the periplasmic space, and the outer membrane, are present in many bacteria, and are ancestrally related to conjugation systems. Recently, the complete structure of a T4SS has been solved by electron microscopy, shedding light on several mechanistic...

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“…Brucella operates systems to move DNA or proteins into the susceptible cells, having these as an important role in bacterial virulence. In Brucella spp., the VirB T4SS allows development of pathogenesis in the generation of a niche inside the host cell and is involved in protein translocation across the cell envelope [41,42].…”

Section: The Pathogenicitymentioning

confidence: 99%

New Scenarios for Brucella suis and Brucella melitensis

Samartino

Arregui

Martino³

2017

Curr Clin Micro Rpt

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Purpose of Review We pretend to highlight the most important advances reached in the last few years in the biology of Brucella suis and Brucella melitensis and focus attention on new tools for the comprehension, prevention and control of these zoonotic agents. Recent Findings Important progress lately done in the field of pathogenesis is presented here. This involves current studies on proteins involved in the survival and antigenic structure of Brucella, as well as the findings of how Brucella has achieved modifications in order to adapt, replicate, survive and modulate the host´s immune system, improve the knowledge of the performance of these bacteria. Summary Consequently, better approaches for vaccinology and diagnostic techniques are developed. Relevant epidemiological issues based on changes in the highly conserved genome of these bacteria will be valuable tools to describe outbreaks and disease status, along with risk factors that would otherwise be difficult to analyze.

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Brucella T4SS: the VIP pass inside host cells

Cited by 43 publications

References 57 publications

Brucella abortus Depends on Pyruvate Phosphate Dikinase and Malic Enzyme but Not on Fbp and GlpX Fructose-1,6-Bisphosphatases for Full Virulence in Laboratory Models

Brucella abortus Depends on Pyruvate Phosphate Dikinase and Malic Enzyme but Not on Fbp and GlpX Fructose-1,6-Bisphosphatases for Full Virulence in Laboratory Models

VirJ Is a Brucella Virulence Factor Involved in the Secretion of Type IV Secreted Substrates

New Scenarios for Brucella suis and Brucella melitensis

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