A CRISPR-enhanced metagenomic NGS test to improve pandemic preparedness.

The lack of preparedness for detecting and responding to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen (i.e., COVID-19) has caused enormous harm to public health and the economy.

LuxR Solos from Environmental Fluorescent Pseudomonads.

LuxR solos are related to quorum sensing (QS) LuxR family regulators; however, they lack a cognate LuxI family protein. LuxR solos are widespread and almost exclusively found in proteobacteria. In this study, we investigated the distribution and conservation of LuxR solos in the fluorescent pseudomonads group.

Pangenome Analytics Reveal Two-Component Systems as Conserved Targets in ESKAPEE Pathogens.

The two-component system (TCS) helps bacteria sense and respond to environmental stimuli through histidine kinases and response regulators. TCSs are the largest family of multistep signal transduction processes, and they are involved in many important cellular processes such as antibiotic resistance, pathogenicity, quorum sensing, osmotic stress, and biofilms. Here, we perform the first comprehensive study to highlight the role of TCSs as potential drug targets against ESKAPEE (, , , , , spp.

Elucidation of Regulatory Modes for Five Two-Component Systems in Escherichia coli Reveals Novel Relationships.

uses two-component systems (TCSs) to respond to environmental signals. TCSs affect gene expression and are parts of 's global transcriptional regulatory network (TRN). Here, we identified the regulons of five TCSs in MG1655: BaeSR and CpxAR, which were stimulated by ethanol stress; KdpDE and PhoRB, induced by limiting potassium and phosphate, respectively; and ZraSR, stimulated by zinc.

The Bitome: digitized genomic features reveal fundamental genome organization.

A genome contains the information underlying an organism's form and function. Yet, we lack formal framework to represent and study this information. Here, we introduce the Bitome, a matrix composed of binary digits (bits) representing the genomic positions of genomic features.

Metabolic and genetic basis for auxotrophies in Gram-negative species.

Auxotrophies constrain the interactions of bacteria with their environment, but are often difficult to identify. Here, we develop an algorithm (AuxoFind) using genome-scale metabolic reconstruction to predict auxotrophies and apply it to a series of available genome sequences of over 1,300 Gram-negative strains. We identify 54 auxotrophs, along with the corresponding metabolic and genetic basis, using a pangenome approach, and highlight auxotrophies conferring a fitness advantage in vivo.

The Escherichia coli transcriptome mostly consists of independently regulated modules.

Underlying cellular responses is a transcriptional regulatory network (TRN) that modulates gene expression. A useful description of the TRN would decompose the transcriptome into targeted effects of individual transcriptional regulators. Here, we apply unsupervised machine learning to a diverse compendium of over 250 high-quality Escherichia coli RNA-seq datasets to identify 92 statistically independent signals that modulate the expression of specific gene sets.

Pseudogene repair driven by selection pressure applied in experimental evolution.

Pseudogenes represent open reading frames that have been damaged by mutations, rendering the gene product non-functional. Pseudogenes are found in many genomes and are not always eliminated, even if they are potentially 'wasteful'. This raises a fundamental question about their prevalence.

The Two-Component System AgrAC Displays Four Distinct Genomic Arrangements That Delineate Genomic Virulence Factor Signatures.

Two-component systems (TCSs) consist of a histidine kinase and a response regulator. Here, we evaluated the conservation of the AgrAC TCS among 149 completely sequenced strains. It is composed of four genes: .

Metabolic re-wiring of isogenic breast epithelial cell lines following epithelial to mesenchymal transition.

Epithelial to mesenchymal transition (EMT) has implications in tumor progression and metastasis. Metabolic alterations have been described in cancer development but studies focused on the metabolic re-wiring that takes place during EMT are still limited. We performed metabolomics profiling of a breast epithelial cell line and its EMT derived mesenchymal phenotype to create genome-scale metabolic models descriptive of both cell lines.

EGFR Signal-Network Reconstruction Demonstrates Metabolic Crosstalk in EMT.

Epithelial to mesenchymal transition (EMT) is an important event during development and cancer metastasis. There is limited understanding of the metabolic alterations that give rise to and take place during EMT. Dysregulation of signalling pathways that impact metabolism, including epidermal growth factor receptor (EGFR), are however a hallmark of EMT and metastasis.

Census of solo LuxR genes in prokaryotic genomes.

luxR genes encode transcriptional regulators that control acyl homoserine lactone-based quorum sensing (AHL QS) in Gram negative bacteria. On the bacterial chromosome, luxR genes are usually found next or near to a luxI gene encoding the AHL signal synthase. Recently, a number of luxR genes were described that have no luxI genes in their vicinity on the chromosome.

ComQXPA quorum sensing systems may not be unique to Bacillus subtilis: a census in prokaryotic genomes.

The comQXPA locus of Bacillus subtilis encodes a quorum sensing (QS) system typical of Gram positive bacteria. It encodes four proteins, the ComQ isoprenyl transferase, the ComX pre-peptide signal, the ComP histidine kinase, and the ComA response regulator. These are encoded by four adjacent genes all situated on the same chromosome strand.

The organization of the quorum sensing luxI/R family genes in Burkholderia.

Members of the Burkholderia genus of Proteobacteria are capable of living freely in the environment and can also colonize human, animal and plant hosts. Certain members are considered to be clinically important from both medical and veterinary perspectives and furthermore may be important modulators of the rhizosphere. Quorum sensing via N-acyl homoserine lactone signals (AHL QS) is present in almost all Burkholderia species and is thought to play important roles in lifestyle changes such as colonization and niche invasion.

Crowd sourcing a new paradigm for interactome driven drug target identification in Mycobacterium tuberculosis.

A decade since the availability of Mycobacterium tuberculosis (Mtb) genome sequence, no promising drug has seen the light of the day. This not only indicates the challenges in discovering new drugs but also suggests a gap in our current understanding of Mtb biology. We attempt to bridge this gap by carrying out extensive re-annotation and constructing a systems level protein interaction map of Mtb with an objective of finding novel drug target candidates.

Classifying the topology of AHL-driven quorum sensing circuits in proteobacterial genomes.

Virulence and adaptability of many Gram-negative bacterial species are associated with an N-acylhomoserine lactone (AHL) gene regulation mechanism called quorum sensing (QS). The arrangement of quorum sensing genes is variable throughout bacterial genomes, although there are unifying themes that are common among the various topological arrangements. A bioinformatics survey of 1,403 complete bacterial genomes revealed characteristic gene topologies in 152 genomes that could be classified into 16 topological groups.