Gamma-Mobile-Trio systems are mobile elements rich in bacterial defensive and offensive tools.

The evolutionary arms race between bacteria and phages led to the emergence of bacterial immune systems whose diversity and dynamics remain poorly understood. Here we use comparative genomics to describe a widespread genetic element, defined by the presence of the Gamma-Mobile-Trio (GMT) proteins, that serves as a reservoir of offensive and defensive tools. We demonstrate, using Vibrio parahaemolyticus as a model, that GMT-containing genomic islands are active mobile elements.

PIX is an N-terminal delivery domain that defines a class of polymorphic T6SS effectors in Enterobacterales.

The type VI secretion system (T6SS), a widespread protein delivery apparatus, plays a role in bacterial competition by delivering toxic effectors into neighboring cells. Identifying new T6SS effectors and deciphering the mechanism that governs their secretion remain major challenges. Here, we report two orphan antibacterial T6SS effectors in the pathogen Pantoea agglomerans (Pa).

A Community-Curated DokuWiki Resource on Diagnostics, Diversity, Pathogenicity, and Genetic Control of Xanthomonads.

Xanthomonads, including and species, constitute a large and significant group of economically and ecologically important plant pathogens. Up-to-date knowledge of these pathogens and their hosts is essential for the development of suitable control measures. Traditional review articles or book chapters have inherent limitations, including static content and rapid obsolescence.

The RIX domain defines a class of polymorphic T6SS effectors and secreted adaptors.

Bacteria use the type VI secretion system (T6SS) to deliver toxic effectors into bacterial or eukaryotic cells during interbacterial competition, host colonization, or when resisting predation. Identifying effectors is a challenging task, as they lack canonical secretion signals or universally conserved domains. Here, we identify a protein domain, RIX, that defines a class of polymorphic T6SS cargo effectors.

T6SS2 effector repertoires.

All strains of the marine bacterium harbor a type VI secretion system (T6SS) named T6SS2, suggesting that this system plays an important role in the life cycle of this emerging pathogen. Although T6SS2 was recently shown to play a role in interbacterial competition, its effector repertoire remains unknown. Here, we employed proteomics to investigate the T6SS2 secretome of two strains, and we identified several antibacterial effectors encoded outside of the main T6SS2 gene cluster.

Multiple T6SSs, Mobile Auxiliary Modules, and Effectors Revealed in a Systematic Analysis of the Vibrio parahaemolyticus Pan-Genome.

Type VI secretion systems (T6SSs) play a major role in interbacterial competition and in bacterial interactions with eukaryotic cells. The distribution of T6SSs and the effectors they secrete vary between strains of the same bacterial species. Therefore, a pan-genome investigation is required to better understand the T6SS potential of a bacterial species of interest.

A DNase Type VI Secretion System Effector Requires Its MIX Domain for Secretion.

Gram-negative bacteria often employ the type VI secretion system (T6SS) to deliver diverse cocktails of antibacterial effectors into rival bacteria. In many cases, even when the identity of the delivered effectors is known, their toxic activity and mechanism of secretion are not. Here, we investigate VPA1263, a Vibrio parahaemolyticus T6SS effector that belongs to a widespread class of polymorphic effectors containing a MIX domain.

A binary effector module secreted by a type VI secretion system.

Gram-negative bacteria use type VI secretion systems (T6SSs) to deliver toxic effector proteins into neighboring cells. Cargo effectors are secreted by binding noncovalently to the T6SS apparatus. Occasionally, effector secretion is assisted by an adaptor protein, although the adaptor itself is not secreted.

Formylglycine-Generating Enzyme-Like Proteins Constitute a Novel Family of Widespread Type VI Secretion System Immunity Proteins.

Competition is a critical aspect of bacterial life, as it enables niche establishment and facilitates the acquisition of essential nutrients. Warfare between Gram-negative bacteria is largely mediated by the type VI secretion system (T6SS), a dynamic nanoweapon that delivers toxic effector proteins from an attacking cell to adjacent bacteria in a contact-dependent manner. Effector-encoding bacteria prevent self-intoxication and kin cell killing by the expression of immunity proteins, which neutralize effector toxicity by specifically binding their cognate effector and either occluding its active site or preventing the structural rearrangements necessary for effector activation.

Trends in Molecular Diagnosis and Diversity Studies for Phytosanitary Regulated .

Bacteria in the genus infect a wide range of crops and wild plants, with most species responsible for plant diseases that have a global economic and environmental impact on the seed, plant, and food trade. Infections by spp. cause a wide variety of non-specific symptoms, making their identification difficult.

A novel class of polymorphic toxins in Bacteroidetes.

Bacteroidetes are Gram-negative bacteria that are abundant in the environment as well as in the gut microbiota of animals. Many bacteroidetes encode large proteins containing an N-terminal domain of unknown function, named TANFOR. In this work, we show that TANFOR-containing proteins carry polymorphic C-terminal toxin domains with predicted antibacterial and anti-eukaryotic activities.

A comparative genomics methodology reveals a widespread family of membrane-disrupting T6SS effectors.

Gram-negative bacteria deliver effectors via the type VI secretion system (T6SS) to outcompete their rivals. Each bacterial strain carries a different arsenal of effectors; the identities of many remain unknown. Here, we present an approach to identify T6SS effectors encoded in bacterial genomes of interest, without prior knowledge of the effectors' domain content or genetic neighborhood.

A modular effector with a DNase domain and a marker for T6SS substrates.

Bacteria deliver toxic effectors via type VI secretion systems (T6SSs) to dominate competitors, but the identity and function of many effectors remain unknown. Here we identify a Vibrio antibacterial T6SS effector that contains a previously undescribed, widespread DNase toxin domain that we call PoNe (Polymorphic Nuclease effector). PoNe belongs to a diverse superfamily of PD-(D/E)xK phosphodiesterases, and is associated with several toxin delivery systems including type V, type VI, and type VII.

The Antibacterial and Anti-Eukaryotic Type VI Secretion System MIX-Effector Repertoire in .

is a widespread family of aquatic bacteria that includes emerging pathogens and symbionts. Many harbor a type VI secretion system (T6SS), which is a secretion apparatus used to deliver toxins, termed effectors, into neighboring cells. T6SSs mediate both antibacterial and anti-eukaryotic activities.

The Xanthomonas euvesicatoria type III effector XopAU is an active protein kinase that manipulates plant MAP kinase signaling.

The Gram-negative bacterium Xanthomonas euvesicatoria (Xe) is the causal agent of bacterial spot disease of pepper and tomato. Xe delivers effector proteins into host cells through the type III secretion system to promote disease. Here, we show that the Xe effector XopAU, which is conserved in numerous Xanthomonas species, is a catalytically active protein kinase and contributes to the development of disease symptoms in pepper plants.

Ancestral acquisitions, gene flow and multiple evolutionary trajectories of the type three secretion system and effectors in Xanthomonas plant pathogens.

Deciphering the evolutionary history and transmission patterns of virulence determinants is necessary to understand the emergence of novel pathogens. The main virulence determinant of most pathogenic proteobacteria is the type three secretion system (T3SS). The Xanthomonas genus includes bacteria responsible for numerous epidemics in agroecosystems worldwide and represents a major threat to plant health.

Expression of Pseudomonas syringae type III effectors in yeast under stress conditions reveals that HopX1 attenuates activation of the high osmolarity glycerol MAP kinase pathway.

The Gram-negative bacterium Pseudomonas syringae pv. tomato (Pst) is the causal agent of speck disease in tomato. Pst pathogenicity depends on a type III secretion system that delivers effector proteins into host cells, where they promote disease by manipulating processes to the advantage of the pathogen.

A simple yeast-based strategy to identify host cellular processes targeted by bacterial effector proteins.

Bacterial effector proteins, which are delivered into the host cell via the type III secretion system, play a key role in the pathogenicity of gram-negative bacteria by modulating various host cellular processes to the benefit of the pathogen. To identify cellular processes targeted by bacterial effectors, we developed a simple strategy that uses an array of yeast deletion strains fitted into a single 96-well plate. The array is unique in that it was optimized computationally such that despite the small number of deletion strains, it covers the majority of genes in the yeast synthetic lethal interaction network.

Ssz1 restores endoplasmic reticulum-associated protein degradation in cells expressing defective cdc48-ufd1-npl4 complex by upregulating cdc48.

The endoplasmic reticulum (ER)-associated protein degradation (ERAD) pathway eliminates aberrant proteins from the ER. The key role of Cdc48p-Ufd1p-Npl4p is indicated by impaired ERAD in Saccharomyces cerevisiae with mutations in any of this complex's genes. We identified SSZ1 in genetic screens for cdc48-10 suppressors and show that it upregulates Cdc48p via the pleiotropic drug resistance (PDR) network.

EGFR juxtamembrane domain, membranes, and calmodulin: kinetics of their interaction.

Calcium/calmodulin (Ca/CaM) binds to the intracellular juxtamembrane domain (JMD) of the epidermal growth factor receptor (EGFR). The basic JMD also binds to acidic lipids in the inner leaflet of the plasma membrane, and this interaction may contribute an extra level of autoinhibition to the receptor. Binding of a ligand to the EGFR produces a rapid increase in intracellular calcium, [Ca2+]i, and thus Ca/CaM.

Endoplasmic reticulum glucosidase II is inhibited by its end products.

The calnexin/calreticulin cycle is a quality control system responsible for promoting the folding of newly synthesized glycoproteins entering the endoplasmic reticulum (ER). The association of calnexin and calreticulin with the glycoproteins is regulated by ER glucosidase II, which hydrolyzes Glc 2Man X GlcNAc 2 glycans to Glc 1Man X GlcNAc 2 and further to Glc 0Man X GlcNAc 2 ( X represents any number between 5 and 9). To gain new insights into the reaction mechanism of glucosidase II, we developed a kinetic model that describes the interactions between glucosidase II, calnexin/calreticulin, and the glycans.

Intravenous immunoglobulin enhances the clearance of fibrillar amyloid-beta peptide.

Intravenous immunoglobulin (IVIg), a purified immunoglobulin fraction manufactured from the blood of healthy humans, is an FDA-approved treatment for many immune and inflammatory diseases. Recent studies have demonstrated that IVIg therapy has several positive effects on patients with Alzheimer's disease (AD). These include improving cognitive functions and lowering the level of soluble amyloid-beta peptide (AbetaP) in the brain.

Systematic search for the rate constants that control the exocytotic process from chromaffin cells by a genetic algorithm.

We have recently created a kinetic model that reproduces the dynamics of exocytosis with high accuracy. The reconstruction necessitated a search, in a multi-dimensional parameter space, for 37 parameters that described the system, with no assurance that the parameters, which reconstructed the observations, are a unique set. In the present study, a Genetic Algorithm (GA) was used for a thorough search in the unknown parameter space, using a strategy of gradual increase of the complexity of the analyzed input data.