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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    • "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.
    Ecotoxicology and Environmental Safety 12/2015; 122:186-192. DOI:10.1016/j.ecoenv.2015.07.028 · 2.76 Impact Factor
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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.
    Cell Reports 08/2015; 12(8). DOI:10.1016/j.celrep.2015.07.043 · 8.36 Impact Factor
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    • "Prokaryotic cells employ two redox-sensing regulons, OxyR and SoxRS, to sense oxidative stress signals and subsequently activate defense mechanisms [95]. The SoxRS regulon has not been found in Bacteroidetes [96], [97]. The oxyR gene (D505_12281) is, however, present in the E. anophelis genome and is located in proximity to the antioxidant genes catalase (D505_12286) and manganese superoxide dismutase (MnSOD) (D505_12271). "
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    ABSTRACT: Elizabethkingia anophelis is a dominant bacterial species in the gut ecosystem of the malaria vector mosquito Anopheles gambiae. We recently sequenced the genomes of two strains of E. anophelis, R26T and Ag1, isolated from different strains of A. gambiae. The two bacterial strains are identical with a few exceptions. Phylogenetically, Elizabethkingia is closer to Chryseobacterium and Riemerella than to Flavobacterium. In line with other Bacteroidetes known to utilize various polymers in their ecological niches, the E. anophelis genome contains numerous TonB dependent transporters with various substrate specificities. In addition, several genes belonging to the polysaccharide utilization system and the glycoside hydrolase family were identified that could potentially be of benefit for the mosquito carbohydrate metabolism. In agreement with previous reports of broad antibiotic resistance in E. anophelis, a large number of genes encoding efflux pumps and β-lactamases are present in the genome. The component genes of resistance-nodulation-division type efflux pumps were found to be syntenic and conserved in different taxa of Bacteroidetes. The bacterium also displays hemolytic activity and encodes several hemolysins that may participate in the digestion of erythrocytes in the mosquito gut. At the same time, the OxyR regulon and antioxidant genes could provide defense against the oxidative stress that is associated with blood digestion. The genome annotation and comparative genomic analysis revealed functional characteristics associated with the symbiotic relationship with the mosquito host.
    PLoS ONE 05/2014; 9(5):e97715. DOI:10.1371/journal.pone.0097715 · 3.23 Impact Factor
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