The putative type 4 secretion system effector BspD is involved in maintaining envelope integrity of the pathogen .

Unlabelled: Brucellosis is a debilitating disease caused by the Gram-negative, facultative intracellular zoonotic pathogen En route to its intracellular replicative niche, encounters various stressful environments that may compromise envelope integrity. Here we show that the proposed type 4 secretion system (T4SS) effector BspD is a conserved protein of the Rhizobiales, which does not show signs of co-evolution with the presence of a T4SS or a certain lifestyle. We further present data indicating that BspD is critical for the envelope integrity of in the stationary phase and in the presence of EDTA, a compound known to destabilize the outer membrane.

Cutting Edge: Redundant Roles for MHC Class II-, CD1d-, and MR1-restricted T Cells in Clearing Bartonella Infection.

The importance of unconventional T cells for mucosal immunity is firmly established but for systemic bacterial infection remains less well defined. In this study, we explored the role of various T cell subsets in murine Bartonella infection, which establishes persistent bacteremia unless controlled by antibacterial Abs. We found that αβ T cells are essential for Ab production against and clearance of B.

Translocation of YopJ family effector proteins through the VirB/VirD4 T4SS of .

The evolutionary conserved YopJ family comprises numerous type-III-secretion system (T3SS) effectors of diverse mammalian and plant pathogens that acetylate host proteins to dampen immune responses. Acetylation is mediated by a central acetyltransferase domain that is flanked by conserved regulatory sequences, while a nonconserved N-terminal extension encodes the T3SS-specific translocation signal. spp.

Structure-function analysis of the cyclic β-1,2-glucan synthase from Agrobacterium tumefaciens.

The synthesis of complex sugars is a key aspect of microbial biology. Cyclic β-1,2-glucan (CβG) is a circular polysaccharide critical for host interactions of many bacteria, including major pathogens of humans (Brucella) and plants (Agrobacterium). CβG is produced by the cyclic glucan synthase (Cgs), a multi-domain membrane protein.

Host cell egress of Brucella abortus requires BNIP3L-mediated mitophagy.

The facultative intracellular pathogen Brucella abortus interacts with several organelles of the host cell to reach its replicative niche inside the endoplasmic reticulum. However, little is known about the interplay between the intracellular bacteria and the host cell mitochondria. Here, we showed that B.

Guided-deconvolution for correlative light and electron microscopy.

Correlative light and electron microscopy is a powerful tool to study the internal structure of cells. It combines the mutual benefit of correlating light (LM) and electron (EM) microscopy information. The EM images only contain contrast information.

Mechanism of cyclic β-glucan export by ABC transporter Cgt of Brucella.

Polysaccharides play critical roles in bacteria, including the formation of protective capsules and biofilms and establishing specific host cell interactions. Their transport across membranes is often mediated by ATP-binding cassette (ABC) transporters, which utilize ATP to translocate diverse molecules. Cyclic β-glucans (CβGs) are critical for host interaction of the Rhizobiales, including the zoonotic pathogen Brucella.

: A Model Organism for Studying Infection and .

spp. are Gram-negative facultative intracellular pathogens that infect diverse mammals and cause a long-lasting intra-erythrocytic bacteremia in their natural host. These bacteria translocate effector proteins (Beps) into host cells their VirB/VirD4 type 4 secretion system (T4SS) in order to subvert host cellular functions, thereby leading to the downregulation of innate immune responses.

Antibiotic persistence of intracellular Brucella abortus.

Background: Human brucellosis caused by the facultative intracellular pathogen Brucella spp. is an endemic bacterial zoonosis manifesting as acute or chronic infections with high morbidity. Treatment typically involves a combination therapy of two antibiotics for several weeks to months, but despite this harsh treatment relapses occur at a rate of 5-15%.

Identification of the autotransporter CFA as a protective antigen and hypervariable target of neutralizing antibodies in mice.

The bacterial genus comprises numerous emerging pathogens that cause a broad spectrum of disease manifestations in humans. The targets and mechanisms of the anti- immune defense are ill-defined and bacterial immune evasion strategies remain elusive. We found that experimentally infected mice resolved infection by mounting antibody responses that neutralized the bacteria, preventing their attachment to erythrocytes and suppressing bacteremia independent of complement or Fc receptors.

Adaptive immune defense prevents Bartonella persistence upon trans-placental transmission.

Vertical transmission of Bartonella infection has been reported for several mammalian species including mice and humans. Accordingly, it is commonly held that acquired immunological tolerance contributes critically to the high prevalence of Bartonellae in wild-ranging rodent populations. Here we studied an experimental model of Bartonella infection in mice to assess the impact of maternal and newborn immune defense on vertical transmission and bacterial persistence in the offspring, respectively.

The Impact of VirB/VirD4 Type IV Secretion System Effectors on Eukaryotic Host Cells.

spp. are facultative intracellular pathogens that infect a wide range of mammalian hosts including humans. The VirB/VirD4 type IV secretion system (T4SS) is a key virulence factor utilized to translocate effector proteins (Beps) into host cells in order to subvert their functions.

Evolutionary Diversification of Host-Targeted Effectors Proteins Derived from a Conserved FicTA Toxin-Antitoxin Module.

Proteins containing a FIC domain catalyze AMPylation and other post-translational modifications (PTMs). In bacteria, they are typically part of FicTA toxin-antitoxin modules that control conserved biochemical processes such as topoisomerase activity, but they have also repeatedly diversified into host-targeted virulence factors. Among these, effector proteins (Beps) comprise a particularly diverse ensemble of FIC domains that subvert various host cellular functions.

Structural basis for selective AMPylation of Rac-subfamily GTPases by effector protein 1 (Bep1).

Small GTPases of the Ras-homology (Rho) family are conserved molecular switches that control fundamental cellular activities in eukaryotic cells. As such, they are targeted by numerous bacterial toxins and effector proteins, which have been intensively investigated regarding their biochemical activities and discrete target spectra; however, the molecular mechanism of target selectivity has remained largely elusive. Here we report a bacterial effector protein that selectively targets members of the Rac subfamily in the Rho family of small GTPases but none in the closely related Cdc42 or RhoA subfamilies.

Bartonella effector protein C mediates actin stress fiber formation via recruitment of GEF-H1 to the plasma membrane.

Bartonellae are Gram-negative facultative-intracellular pathogens that use a type-IV-secretion system (T4SS) to translocate a cocktail of Bartonella effector proteins (Beps) into host cells to modulate diverse cellular functions. BepC was initially reported to act in concert with BepF in triggering major actin cytoskeletal rearrangements that result in the internalization of a large bacterial aggregate by the so-called 'invasome'. Later, infection studies with bepC deletion mutants and ectopic expression of BepC have implicated this effector in triggering an actin-dependent cell contractility phenotype characterized by fragmentation of migrating cells due to deficient rear detachment at the trailing edge, and BepE was shown to counterbalance this remarkable phenotype.

A Bartonella Effector Acts as Signaling Hub for Intrinsic STAT3 Activation to Trigger Anti-inflammatory Responses.

Chronically infecting pathogens avoid clearance by the innate immune system by promoting premature transition from an initial pro-inflammatory response toward an anti-inflammatory tissue-repair response. STAT3, a central regulator of inflammation, controls this transition and thus is targeted by numerous chronic pathogens. Here, we show that BepD, an effector of the chronic bacterial pathogen Bartonella henselae targeted to infected host cells, establishes an exceptional pathway for canonical STAT3 activation, thereby impairing secretion of pro-inflammatory TNF-α and stimulating secretion of anti-inflammatory IL-10.

PyBDA: a command line tool for automated analysis of big biological data sets.

Background: Analysing large and high-dimensional biological data sets poses significant computational difficulties for bioinformaticians due to lack of accessible tools that scale to hundreds of millions of data points.

Results: We developed a novel machine learning command line tool called PyBDA for automated, distributed analysis of big biological data sets. By using Apache Spark in the backend, PyBDA scales to data sets beyond the size of current applications.

A Role for the VPS Retromer in Intracellular Replication Revealed by Genomewide siRNA Screening.

, the agent causing brucellosis, is a major zoonotic pathogen with worldwide distribution. resides and replicates inside infected host cells in membrane-bound compartments called containing vacuoles (BCVs). Following uptake, resides in endosomal BCVs (eBCVs) that gradually mature from early to late endosomal features.

Bartonella gene transfer agent: Evolution, function, and proposed role in host adaptation.

The processes underlying host adaptation by bacterial pathogens remain a fundamental question with relevant clinical, ecological, and evolutionary implications. Zoonotic pathogens of the genus Bartonella constitute an exceptional model to study these aspects. Bartonellae have undergone a spectacular diversification into multiple species resulting from adaptive radiation.

Versatility of the BID Domain: Conserved Function as Type-IV-Secretion-Signal and Secondarily Evolved Effector Functions Within -Infected Host Cells.

spp. are facultative intracellular pathogens that infect a wide range of mammalian hosts including humans. In order to subvert cellular functions and the innate immune response of their hosts, these pathogens utilize a VirB/VirD4 type-IV-secretion (T4S) system to translocate effector proteins (Beps) into host cells.

Publisher Correction: Definitions and guidelines for research on antibiotic persistence.

In Figure 2b, the minimal duration for killing (MDK) 99% of tolerant cells was erroneously labelled as MDK99.99 instead of MDK99. This has now been corrected in all versions of the Review.

Definitions and guidelines for research on antibiotic persistence.

Increasing concerns about the rising rates of antibiotic therapy failure and advances in single-cell analyses have inspired a surge of research into antibiotic persistence. Bacterial persister cells represent a subpopulation of cells that can survive intensive antibiotic treatment without being resistant. Several approaches have emerged to define and measure persistence, and it is now time to agree on the basic definition of persistence and its relation to the other mechanisms by which bacteria survive exposure to bactericidal antibiotic treatments, such as antibiotic resistance, heteroresistance or tolerance.

Quantitative contribution of efflux to multi-drug resistance of clinical Escherichia coli and Pseudomonas aeruginosa strains.

Background: Efflux pumps mediate antimicrobial resistance in several WHO critical priority bacterial pathogens. However, most available data come from laboratory strains. The quantitative relevance of efflux in more relevant clinical isolates remains largely unknown.