transcriptomics
Research Article | Host-Microbe BiologyDrug Repurposing of Bromodomain Inhibitors as Potential Novel Therapeutic Leads for Lymphatic Filariasis Guided by Multispecies TranscriptomicsThe current treatment regimen for lymphatic filariasis is mostly microfilaricidal. In an effort to identify new drug candidates for lymphatic filariasis, we conducted a three-way transcriptomics/systems biology study of one of the causative agents of lymphatic filariasis, Brugia malayi, its Wolbachia endosymbiont wBm, and its vector host...
Research Article | Molecular Biology and PhysiologyComplex Responses to Hydrogen Peroxide and Hypochlorous Acid by the Probiotic Bacterium Lactobacillus reuteriReactive oxidants, including hydrogen peroxide and hypochlorous acid, are antimicrobial compounds produced by the immune system during inflammation. Little is known, however, about how many important types of bacteria present in the human microbiome respond to these oxidants, especially commensal and other health-associated species. We have now mapped the stress response to both H2O2 and HOCl in the intestinal...
Editor's Pick Research Article | Host-Microbe BiologyDual RNA-seq in Streptococcus pneumoniae Infection Reveals Compartmentalized Neutrophil Responses in Lung and Pleural SpaceThe factors that regulate the passage of bacteria between different anatomical compartments are unclear. We have used an experimental model of infection with Streptococcus pneumoniae to examine the host and bacterial factors involved in the passage of bacteria from the lung to the pleural space. The transcriptional profile of host and bacterial cells within the...
Research Article | Synthetic BiologySystems Analyses Reveal the Resilience of Escherichia coli Physiology during Accumulation and Export of the Nonnative Organic Acid CitramalateCitramalate is an attractive biotechnology target because it is a precursor of methylmethacrylate, which is used to manufacture Perspex and other high-value products. Engineered E. coli strains are able to produce high titers of citramalate, despite having to express a foreign enzyme and tolerate the presence of a nonnative biochemical. A systems analysis of the...
Research Article | Molecular Biology and PhysiologyMinor Isozymes Tailor Yeast Metabolism to Carbon AvailabilityGene duplication is one of the main evolutionary paths to new protein function. Typically, duplicated genes either accumulate mutations and degrade into pseudogenes or are retained and diverge in function. Some duplicated genes, however, show long-term persistence without apparently acquiring new function. An important class of isozymes consists of those that catalyze the same reaction in the same compartment, where knockout of one...
Research Article | Molecular Biology and PhysiologySystems-Level Analysis of Oxygen Exposure in Zymomonas mobilis: Implications for Isoprenoid ProductionMicrobially generated biofuels and bioproducts have the potential to provide a more environmentally sustainable alternative to fossil-fuel-derived products. In particular, isoprenoids, a diverse class of natural products, are chemically suitable for use as high-grade transport fuels and other commodity molecules. However, metabolic engineering for increased production of isoprenoids and other bioproducts is limited by an incomplete...
Research Article | Novel Systems Biology TechniquesMetabolic Responses to Polymyxin Treatment in Acinetobacter baumannii ATCC 19606: Integrating Transcriptomics and Metabolomics with Genome-Scale Metabolic ModelingCombating antimicrobial resistance has been highlighted as a critical global health priority. Due to the drying drug discovery pipeline, polymyxins have been employed as the last-line therapy against Gram-negative “superbugs”; however, the detailed mechanisms of antibacterial killing remain largely unclear, hampering the improvement of polymyxin therapy. Our integrative modeling using the constructed genome-scale metabolic model i...
Research Article | Therapeutics and PreventionComparative Metabolomics and Transcriptomics Reveal Multiple Pathways Associated with Polymyxin Killing in Pseudomonas aeruginosaPseudomonas aeruginosa has been highlighted by the recent WHO Global Priority Pathogen List due to multidrug resistance. Without new antibiotics, polymyxins remain a last-line therapeutic option for this difficult-to-treat pathogen. The emergence of polymyxin resistance highlights the growing threat to our already very limited antibiotic armamentarium and the urgency...
Editor's Pick Research Article | Host-Microbe BiologyPersistent Interactions with Bacterial Symbionts Direct Mature-Host Cell Morphology and Gene Expression in the Squid-Vibrio SymbiosisA long-term relationship between symbiotic partners is often characterized by development and maturation of host structures that harbor the symbiont cells over the host’s lifetime. To understand the mechanisms involved in symbiosis maintenance more fully, we studied the mature bobtail squid, whose light-emitting organ, under experimental conditions, can be transiently or persistently colonized by...
Research Article | Novel Systems Biology TechniquesModeling the Pseudomonas Sulfur Regulome by Quantifying the Storage and Communication of InformationBacteria sense and respond to their environments using a sophisticated array of sensors and regulatory networks to optimize their fitness and survival in a constantly changing environment. Understanding how these regulatory and sensory networks work will provide the capacity to predict bacterial behaviors and, potentially, to manipulate their interactions with an environment or host. Leveraging the information theory provides useful...