Molecular Biology and Physiology
Research Article | Molecular Biology and PhysiologyChemogenomic Screen for Imipenem Resistance in Gram-Negative BacteriaGram-negative carbapenem-resistant bacteria are a major threat to global health. The use of genome-wide screening approaches to probe for genes or mutations enabling resistance can lead to identification of molecular markers for diagnostics applications. We describe an approach called Mut-Seq that couples chemical mutagenesis and next-generation sequencing for studying resistance to imipenem in the Gram-negative bacteria...
Research Article | Molecular Biology and PhysiologyMetabolic Modeling of Streptococcus mutans Reveals Complex Nutrient Requirements of an Oral PathogenTooth decay is the most prevalent chronic disease in the United States. Decay is caused by the bacterium Streptococcus mutans, an oral pathogen that ferments sugars into tooth-destroying lactic acid. We constructed a complete metabolic model of S. mutans to systematically investigate how the...
Research Article | Molecular Biology and PhysiologyGenomewide Analysis of Mode of Action of the S-Adenosylmethionine Analogue Sinefungin in Leishmania infantumThe two main cellular metabolic one-carbon donors are reduced folates and S-adenosylmethionine, whose biosynthetic pathways have proven highly effective in chemotherapeutic interventions in various cell types. Sinefungin, a nucleoside analogue of S-adenosylmethionine, was shown to have potent activity against the protozoan parasite Leishmania. Here, we studied resistance to sinefungin using whole-genome...
Research Article | Molecular Biology and PhysiologyConserved Central Intraviral Protein Interactome of the Herpesviridae FamilyHerpesviruses are an important socioeconomic burden for both humans and livestock. Throughout their long evolutionary history, individual herpesvirus species have developed remarkable host specificity, while collectively the Herpesviridae family has evolved to infect a large variety of eukaryotic hosts. The development of approaches to fight herpesvirus infections has been hampered by the complexity of herpesviruses’ genomes,...
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...
Research Article | Molecular Biology and PhysiologySulfur Assimilation Alters Flagellar Function and Modulates the Gene Expression Landscape of Serratia marcescensSerratia marcescens is a versatile bacterial species that inhabits diverse environmental niches and is capable of pathogenic interactions with host organisms ranging from insects to humans. This report demonstrates for the first time the extensive impacts that environmental sulfate availability and cysteine biosynthesis have on the transcriptome of...
Research Article | Molecular Biology and PhysiologyHfq Globally Binds and Destabilizes sRNAs and mRNAs in Yersinia pestisDiscovered in 1968 as an Escherichia coli host factor that was essential for replication of the bacteriophage Qβ, the Hfq protein is a ubiquitous and highly abundant RNA-binding protein in many bacteria. With the assistance of Hfq, small RNAs in bacteria play important roles in regulating the stability and translation of mRNAs by base pairing. In this study, we want...
Research Article | Molecular Biology and PhysiologyGenomewide Assessment of Mycobacterium tuberculosis Conditionally Essential Metabolic PathwaysMycobacterium tuberculosis causes 10 million cases of tuberculosis (TB), resulting in over 1 million deaths each year. TB therapy is challenging because it requires a minimum of 6 months of treatment with multiple drugs. Protracted treatment times and the emergent spread of drug-resistant M. tuberculosis...
Research Article | Molecular Biology and PhysiologyA Novel Cys2His2 Zinc Finger Homolog of AZF1 Modulates Holocellulase Expression in Trichoderma reeseiIn this work, we used a systems biology approach to map new regulatory interactions in Trichoderma reesei controlling the expression of genes encoding cellulase and hemicellulase. By integrating transcriptomics related to complex biomass degradation, we were able to identify a novel transcriptional regulator which is able to activate the expression of these genes in...
Editor's Pick Research Article | Molecular Biology and PhysiologyAlteration of Proteomes in First-Generation Cultures of Bacillus pumilus Spores Exposed to Outer SpaceSpore-forming bacteria are well known for their resistance to harsh environments and are of concern for spreading contamination to extraterrestrial bodies during future life detection missions. Bacillus pumilus has been regularly isolated from spacecraft-associated surfaces and exhibited unusual resistance to ultraviolet light and other sterilization techniques. A...