Autoregulation ensures vertical transmission of the linear prophage GIL01.

Betatectiviruses are prophages consisting of linear extrachromosomal genomes without obvious plasmid modules. It remains unclear how betatectiviruses are maintained in low-copy numbers in host cells and how they are vertically transmitted. Phage GIL01 is a model betatectivirus that infects the mosquito pathogen Bacillus thuringiensis serovar israelensis.

Protein interaction networks in the vasculature prioritize genes and pathways underlying coronary artery disease.

Population-based association studies have identified many genetic risk loci for coronary artery disease (CAD), but it is often unclear how genes within these loci are linked to CAD. Here, we perform interaction proteomics for 11 CAD-risk genes to map their protein-protein interactions (PPIs) in human vascular cells and elucidate their roles in CAD. The resulting PPI networks contain interactions that are outside of known biology in the vasculature and are enriched for genes involved in immunity-related and arterial-wall-specific mechanisms.

Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia.

Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons.

Protein interaction studies in human induced neurons indicate convergent biology underlying autism spectrum disorders.

Autism spectrum disorders (ASDs) have been linked to genes with enriched expression in the brain, but it is unclear how these genes converge into cell-type-specific networks. We built a protein-protein interaction network for 13 ASD-associated genes in human excitatory neurons derived from induced pluripotent stem cells (iPSCs). The network contains newly reported interactions and is enriched for genetic and transcriptional perturbations observed in individuals with ASDs.

A small bacteriophage protein determines the hierarchy over co-residential jumbo phage in Bacillus thuringiensis serovar israelensis.

Bacillus thuringiensis serovar israelensis is the most widely used biopesticide against insects, including vectors of animal and human diseases. Among several extrachromosomal elements, this endospore-forming entomopathogen harbors two bacteriophages: a linear DNA replicon named GIL01 that does not integrate into the chromosome during lysogeny and a circular-jumbo prophage known as pBtic235. Here, we show that GIL01 hinders the induction of cohabiting prophage pBtic235.

The Small DdrR Protein Directly Interacts with the UmuDAb Regulator of the Mutagenic DNA Damage Response in Acinetobacter baumannii.

Acinetobacter baumannii poses a great threat in health care settings worldwide, with clinical isolates displaying an ever-evolving multidrug resistance. In strains of A. baumannii, expression of multiple error-prone polymerase genes are corepressed by UmuDAb, a member of the LexA superfamily, and a small protein, DdrR.

Genoppi is an open-source software for robust and standardized integration of proteomic and genetic data.

Combining genetic and cell-type-specific proteomic datasets can generate biological insights and therapeutic hypotheses, but a technical and statistical framework for such analyses is lacking. Here, we present an open-source computational tool called Genoppi (lagelab.org/genoppi) that enables robust, standardized, and intuitive integration of quantitative proteomic results with genetic data.

Systematic auditing is essential to debiasing machine learning in biology.

Biases in data used to train machine learning (ML) models can inflate their prediction performance and confound our understanding of how and what they learn. Although biases are common in biological data, systematic auditing of ML models to identify and eliminate these biases is not a common practice when applying ML in the life sciences. Here we devise a systematic, principled, and general approach to audit ML models in the life sciences.

Growth effects of N-acylethanolamines on gut bacteria reflect altered bacterial abundances in inflammatory bowel disease.

Inflammatory bowel diseases (IBD) are associated with alterations in gut microbial abundances and lumenal metabolite concentrations, but the effects of specific metabolites on the gut microbiota in health and disease remain largely unknown. Here, we analysed the influences of metabolites that are differentially abundant in IBD on the growth and physiology of gut bacteria that are also differentially abundant in IBD. We found that N-acylethanolamines (NAEs), a class of endogenously produced signalling lipids elevated in the stool of IBD patients and a T-cell transfer model of colitis, stimulated growth of species over-represented in IBD and inhibited that of species depleted in IBD in vitro.

Bacteroides-Derived Sphingolipids Are Critical for Maintaining Intestinal Homeostasis and Symbiosis.

Sphingolipids are structural membrane components and important eukaryotic signaling molecules. Sphingolipids regulate inflammation and immunity and were recently identified as the most differentially abundant metabolite in stool from inflammatory bowel disease (IBD) patients. Commensal bacteria from the Bacteroidetes phylum also produce sphingolipids, but the impact of these metabolites on host pathways is largely uncharacterized.

Structural Insights into Bacteriophage GIL01 gp7 Inhibition of Host LexA Repressor.

Bacteria identify and respond to DNA damage using the SOS response. LexA, a central repressor in the response, has been implicated in the regulation of lysogeny in various temperate bacteriophages. During infection of Bacillus thuringiensis with GIL01 bacteriophage, LexA represses the SOS response and the phage lytic cycle by binding DNA, an interaction further stabilized upon binding of a viral protein, gp7.

Author Correction: Gut microbiome structure and metabolic activity in inflammatory bowel disease.

In the Supplementary Tables 2, 4 and 6 originally published with this Article, the authors mistakenly included sample identifiers in the form of UMCGs rather than UMCG IBDs in the validation cohort; this has now been amended.

Gut microbiome structure and metabolic activity in inflammatory bowel disease.

The inflammatory bowel diseases (IBDs), which include Crohn's disease (CD) and ulcerative colitis (UC), are multifactorial chronic conditions of the gastrointestinal tract. While IBD has been associated with dramatic changes in the gut microbiota, changes in the gut metabolome-the molecular interface between host and microbiota-are less well understood. To address this gap, we performed untargeted metabolomic and shotgun metagenomic profiling of cross-sectional stool samples from discovery (n = 155) and validation (n = 65) cohorts of CD, UC and non-IBD control patients.

Lytic gene expression in the temperate bacteriophage GIL01 is activated by a phage-encoded LexA homologue.

The GIL01 bacteriophage is a temperate phage that infects the insect pathogen Bacillus thuringiensis. During the lytic cycle, phage gene transcription is initiated from three promoters: P1 and P2, which control the expression of the early phage genes involved in genome replication and P3, which controls the expression of the late genes responsible for virion maturation and host lysis. Unlike most temperate phages, GIL01 lysogeny is not maintained by a dedicated phage repressor but rather by the host's regulator of the SOS response, LexA.

A Common Mechanism Links Activities of Butyrate in the Colon.

Two biological activities of butyrate in the colon (suppression of proliferation of colonic epithelial stem cells and inflammation) correlate with inhibition of the activity of histone deacetylases. Cellular and biochemical studies of molecules similar in structure to butyrate, but different in molecular details (functional groups, chain-length, deuteration, oxidation level, fluorination, or degree of unsaturation), demonstrated that these activities were sensitive to molecular structure, and were compatible with the hypothesis that butyrate acts by binding to the Zn in the catalytic site of histone deacetylases. Structure-activity relationships drawn from a set of 36 compounds offer a starting point for the design of new compounds targeting the inhibition of histone deacetylases.

A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients.

Background: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract that is associated with changes in the gut microbiome. Here, we sought to identify strain-specific functional correlates with IBD outcomes.

Methods: We performed metagenomic sequencing of monthly stool samples from 20 IBD patients and 12 controls (266 total samples).

The Use and Abuse of LexA by Mobile Genetic Elements.

The SOS response is an essential process for responding to DNA damage in bacteria. The expression of SOS genes is under the control of LexA, a global transcription factor that undergoes self-cleavage during stress to allow the expression of DNA repair functions and delay cell division until the damage is rectified. LexA also regulates genes that are not part of this cell rescue program, and the induction of bacteriophages, the movement of pathogenicity islands, and the expression of virulence factors and bacteriocins are all controlled by this important transcription factor.

Bacteriophage GIL01 gp7 interacts with host LexA repressor to enhance DNA binding and inhibit RecA-mediated auto-cleavage.

The SOS response in Eubacteria is a global response to DNA damage and its activation is increasingly associated with the movement of mobile genetic elements. The temperate phage GIL01 is induced into lytic growth using the host's SOS response to genomic stress. LexA, the SOS transcription factor, represses bacteriophage transcription by binding to a set of SOS boxes in the lysogenic promoter P1.

Identification of a ligand on the Wip1 bacteriophage highly specific for a receptor on Bacillus anthracis.

Tectiviridae is a family of tailless bacteriophages with Gram-negative and Gram-positive hosts. The family model PRD1 and its close relatives all infect a broad range of enterobacteria by recognizing a plasmid-encoded conjugal transfer complex as a receptor. In contrast, tectiviruses with Gram-positive hosts are highly specific to only a few hosts within the same bacterial species.

Identification of five novel tectiviruses in Bacillus strains: analysis of a highly variable region generating genetic diversity.

Our biosphere is abundant with unique and small genes for which no homologs are known. These genes, often referred to as orphans or ORFans, are commonly found in bacteriophage genomes but their origins remain unclear. We discovered five novel tectivirus-like genetic elements by screening more than five-hundred Bacillus strains.

Phage-borne factors and host LexA regulate the lytic switch in phage GIL01.

The Bacillus thuringiensis temperate phage GIL01 does not integrate into the host chromosome but exists stably as an independent linear replicon within the cell. Similar to that of the lambdoid prophages, the lytic cycle of GIL01 is induced as part of the cellular SOS response to DNA damage. However, no CI-like maintenance repressor has been detected in the phage genome, suggesting that GIL01 uses a novel mechanism to maintain lysogeny.

Family portrait of Bacillus cereus and Bacillus weihenstephanensis cereulide-producing strains.

Two thousand Bacillus cereus sensu lato isolates from food and environmental matrices were screened by PCR for the presence of cereulide-producing strains. This survey identified 73 potential emetic strains, most of which originated from non-random food and clinical samplings. None of the 460 Bacillus thuringiensis, Bacillus mycoides and Bacillus pseudomycoides strains were PCR-positive for the cereulide genetic determinants.

GIL16, a new gram-positive tectiviral phage related to the Bacillus thuringiensis GIL01 and the Bacillus cereus pBClin15 elements.

One of the most notable characteristics of Tectiviridae resides in their double-layer coats: the double-stranded DNA is located within a flexible lipoprotein vesicle covered by a rigid protein capsid. Despite their apparent rarity, tectiviruses have an extremely wide distribution compared to other phage groups. Members of this family have been found to infect gram-negative (PRD1 and relatives) as well as gram-positive (Bam35, GIL01, AP50, and phiNS11) hosts.

The Bacillus thuringiensis phage GIL01 encodes two enzymes with peptidoglycan hydrolase activity.

Bacteriophage GIL01, infecting Bacillus thuringiensis serovar israelensis, possesses a linear dsDNA genome of 14,931 bp with proteins attached to its 5' extremities and terminal inverted repeats at both ends. Viral particles are sensitive to organic solvents, suggesting that a lipid membrane is present in the capsid. All these characteristics are reminiscent of those found in members of the Tectiviridae family.