Redox-Active Antibiotics Control Gene Expression and Community Behavior in Divergent Bacteria

Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 01239, USA.
Science (Impact Factor: 33.61). 09/2008; 321(5893):1203-6. DOI: 10.1126/science.1160619
Source: PubMed


It is thought that bacteria excrete redox-active pigments as antibiotics to inhibit competitors. In Pseudomonas aeruginosa, the endogenous antibiotic pyocyanin activates SoxR, a transcription factor conserved in Proteo- and Actinobacteria. In Escherichia coli, SoxR regulates the superoxide stress response. Bioinformatic analysis coupled with gene expression studies in P. aeruginosa and Streptomyces coelicolor revealed that the majority of SoxR regulons in bacteria lack the genes required for stress responses, despite the fact that
many of these organisms still produce redox-active small molecules, which indicates that redox-active pigments play a role
independent of oxidative stress. These compounds had profound effects on the structural organization of colony biofilms in
both P. aeruginosa and S. coelicolor, which shows that “secondary metabolites” play important conserved roles in gene expression and development.

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Available from: Lars E. Dietrich
    • "As reviewed previously (Allen et al. 2010; Huijbers et al. 2015), some environments will harbor ARGs (in some instances irrespective of anthropogenic influence due to spread via environment or wild animals), and more studies are necessary to quantity contributions of varying environments to exposure and transmission. It should be mentioned that some ARGs have functional roles that are independent of resistance, such as efflux and electron transport, and will not always be associated with human activity (Dietrich et al., 2008). With culture-based AR analysis accurately identifying sources of host fecal contamination (Park, Lee and Kim 2015), molecular screening of ARGs may also provide a means of source tracking (Li et al. 2015). "
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    ABSTRACT: An antibiotic resistance (AR) Dashboard application is being developed regarding the occurrence of antibiotic resistance genes (ARG) and bacteria (ARB) in environmental and clinical settings. The application gathers and geospatially maps AR studies, reported occurrence, and antibiograms, which can be downloaded for offline analysis. With the integration of multiple data sets, the database can be used on a regional or global scale to identify hot spots for ARGs and ARB, track and link spread and transmission, quantify environmental or human factors influencing presence and persistence of ARG harboring organisms, differentiate natural ARGs from those distributed via human or animal activity, cluster and compare ARGs connections in different environments and hosts, and identify genes that can be used as proxies to routinely monitor anthropogenic pollution. To initially populate and develop the AR Dashboard, a qPCR ARG array was tested with 30 surface waters, primary influent from three waste water treatment facilities, ten clinical isolates from a regional hospital, and data from previously published studies including river, park soil, and swine farm samples. Interested users are invited to download a beta version (available on iOS or Android), submit AR information using the application, and provide feedback on current and prospective functionalities.
    No preview · Article · Feb 2016 · FEMS Microbiology Ecology
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    • "One of the roles of SoxS is detoxifying reactive oxygen species such as superoxide and nitric oxide (Dietrich et al., 2008). It has also been reported that the upregulation of SoxS by pyocyanin is restricted to bacteria from the family Enterobacteriaceae (Dietrich et al., 2008), which includes E. coli but not B. subtilis. Similar to pyocyanin, NR may have upregulated SoxS production in E. coli, negating the effects of reactive oxygen species at 0.5 and 5 mM NR. "
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    ABSTRACT: Neutral red (NR) is a synthetic phenazine with promising prospect in environmental biotechnology as an electron shuttle. Recently, NR injections into coal seam associated groundwater in Australia (final dissolved NR concentration: 8µM±0.2) were shown to increase methanogenesis up to ten-fold. However, information about NR toxicity to ecological receptors is sorely lacking. The main aim of this study was to investigate the concentration dependent toxicity of NR in microorganisms and plants. Acute toxicity of NR was determined by the modified Microtox™ assay. Microbial viability was determined using Escherichia coli and Bacillus subtilis. Germination and early growth of plants was studied using Lactuca sativa, Daucus carota, Allium cepa and an Australian native Themeda triandra. Lastly, mutagenicity of the coal seam associated groundwater was assessed using the Ames test. The EC50 of acute NR toxicity was determined to be 0.11mM. The EC50 of microbial viability was between 1 and 7.1mM NR. Among the concentrations tested, only 0.01, 0.10 and 100mM of NR significantly affected (p<0.001) germination of L. sativa. The EC50 for root elongation in seeds was between 1.2 and 35.5mM NR. Interestingly, root elongation in seeds was significantly stimulated (p<0.001) between 0.25 and 10mM NR, showing a hormetic effect. A significant increase in mutagenicity was only observed in one of the three wells tested. The results suggest that the average dissolved NR concentration (8µM±0.2) deployed in the field trial at Lithgow State Coal Mine, Australia, appears not to negatively impact the ecological receptors tested in this study. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · Dec 2015 · Ecotoxicology and Environmental Safety
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    • "Recently , it has been reported that lpxC belongs to the OxyR reg - ulon in Pseudomonas ( Wei et al . , 2012 ) , but our study showed that it belongs to both SoxR and SoxS in E . coli . In other bacteria , the preserved SoxR tends to control a distinct set of genes involved in redox - active antibiotic production ( Dietrich et al . , 2008 ) . Based on these facts , it might be the case that OxyR ( or another functional ortholog , PerR , when OxyR is not present ; Chiang and Schellhorn , 2012 ) takes over the roles of SoxR and SoxS . Figure 6 . Evolutionary Perspective on OxyR , SoxR , and SoxS Regulons"
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    ABSTRACT: Three transcription factors (TFs), OxyR, SoxR, and SoxS, play a critical role in transcriptional regulation of the defense system for oxidative stress in bacteria. However, their full genome-wide regulatory potential is unknown. Here, we perform a genome-scale reconstruction of the OxyR, SoxR, and SoxS regulons in Escherichia coli K-12 MG1655. Integrative data analysis reveals that a total of 68 genes in 51 transcription units (TUs) belong to these regulons. Among them, 48 genes showed more than 2-fold changes in expression level under single-TF-knockout conditions. This reconstruction expands the genome-wide roles of these factors to include direct activation of genes related to amino acid biosynthesis (methionine and aromatic amino acids), cell wall synthesis (lipid A biosynthesis and peptidoglycan growth), and divalent metal ion transport (Mn(2+), Zn(2+), and Mg(2+)). Investigating the co-regulation of these genes with other stress-response TFs reveals that they are independently regulated by stress-specific TFs. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
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