# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 1 | 0 | 0.9034 | Constructs for insertional mutagenesis, transcriptional signal localization and gene regulation studies in root nodule and other bacteria. Cassettes have been developed that contain an antibiotic resistance marker with and without a promoterless gusA reporter gene. The nptII (encoding kanamycin resistance) or aacCI (encoding gentamicin resistance) genes were equipped with the tac promoter (Ptac) and the trpA terminator (TtrpA) and then cloned between NotI sites to construct the CAS-Nm (Ptac-nptII-TtrpA) and CAS-Gm (Ptac/PaacCI-aacCI-TtrpA) cassettes. The markers were also cloned downstream to a modified promoterless Escherichia coli gusA gene (containing TGA stop codons in all three reading frames prior to its RBS and start codon) to construct the CAS-GNm (gusA-Ptac-nptII-TtrpA) or CAS-GGm (gusA-Ptac/PaacCI-aacCI-TtrpA) cassettes. Cassettes containing the promoterless gusA create type I fusions with a target DNA sequence to detect transcriptional activity. The promoterless gusA gene has also been cloned into a broad-host-range IncP1 plasmid. This construct will enable transcriptional activity to be monitored in different genetic backgrounds. Each cassette was cloned as a NotI fragment into the NotI site of a pUT derivative to construct four minitransposons. The mTn5-Nm (containing Ptac-nptII-TtrpA) and mTn5-Gm (containing Ptac/PaacCI-aacCI-TtrpA) minitransposons have been constructed specifically for insertional inactivation studies. The minitransposons mTn5-GNm (containing gusA-Ptac-nptII-TtrpA) and mTn5-GGm (containing gusA-Ptac/PaacCI-aacCI-TtrpA) can be used for transcription signal localization or insertional inactivation. The TAC-31R and TAC-105F primers can be used to sequence DNA flanking both sides of CAS-Nm, CAS-Gm, mTn5-Nm and mTn5-Gm. The WIL3 and TAC-105F primers can be used to sequence DNA flanking both sides of CAS-GNm, CAS-GGm, mTn5-GNm and mTn5-GGm. The specific application of these constructs to generate acid- or nodule-inducible fusions is presented. The new constructs provide useful tools for insertional mutagenesis, transcriptional signal localization and gene regulation studies in the root nodule bacteria and possibly other gram-negative bacteria. | 1999 | 10411257 |
| 547 | 1 | 0.8970 | Dual role of OhrR as a repressor and an activator in response to organic hydroperoxides in Streptomyces coelicolor. Organic hydroperoxide resistance in bacteria is achieved primarily through reducing oxidized membrane lipids. The soil-inhabiting aerobic bacterium Streptomyces coelicolor contains three paralogous genes for organic hydroperoxide resistance: ohrA, ohrB, and ohrC. The ohrA gene is transcribed divergently from ohrR, which encodes a putative regulator of MarR family. Both the ohrA and ohrR genes were induced highly by various organic hydroperoxides. The ohrA gene was induced through removal of repression by OhrR, whereas the ohrR gene was induced through activation by OhrR. Reduced OhrR bound to the ohrA-ohrR intergenic region, which contains a central (primary) and two adjacent (secondary) inverted-repeat motifs that overlap with promoter elements. Organic peroxide decreased the binding affinity of OhrR for the primary site, with a concomitant decrease in cooperative binding to the adjacent secondary sites. The single cysteine C28 in OhrR was involved in sensing oxidants, as determined by substitution mutagenesis. The C28S mutant of OhrR bound to the intergenic region without any change in binding affinity in response to organic peroxides. These results lead us to propose a model for the dual action of OhrR as a repressor and an activator in S. coelicolor. Under reduced conditions, OhrR binds cooperatively to the intergenic region, repressing transcription from both genes. Upon oxidation, the binding affinity of OhrR decreases, with a concomitant loss of cooperative binding, which allows RNA polymerase to bind to both the ohrA and ohrR promoters. The loosely bound oxidized OhrR can further activate transcription from the ohrR promoter. | 2007 | 17586628 |
| 305 | 2 | 0.8923 | Toolkit Development for Cyanogenic and Gold Biorecovery Chassis Chromobacterium violaceum. Chromobacterium violaceum has been of interest recently due to its cyanogenic ability and its potential role in environmental sustainability via the biorecovery of gold from electronic waste. However, as with many nonmodel bacteria, there are limited genetic tools to implement the use of this Gram-negative chassis in synthetic biology. We propose a system that involves assaying spontaneous antibiotic resistances and using broad host range vectors to develop episomal vectors for nonmodel Gram-negative bacteria. These developed vectors can subsequently be used to characterize inducible promoters for gene expressions and implementing CRISPRi to inhibit endogenous gene expression for further studies. Here, we developed the first episomal genetic toolkit for C. violaceum consisting of two origins of replication, three antibiotic resistance genes, and four inducible promoter systems. We examined the occurrences of spontaneous resistances of the bacterium to the chosen selection markers to prevent incidences of false positives. We also tested broad host range vectors from four different incompatibility groups and characterized four inducible promoter systems, which potentially can be applied in other Gram-negative nonmodel bacteria. CRISPRi was also implemented to inhibit violacein pigment production in C. violaceum. This systematic toolkit will aid future genetic circuitry building in this chassis and other nonmodel bacteria for synthetic biology and biotechnological applications. | 2020 | 32160465 |
| 545 | 3 | 0.8914 | Characterization of the organic hydroperoxide resistance system of Brucella abortus 2308. The organic hydroperoxide resistance protein Ohr has been identified in numerous bacteria where it functions in the detoxification of organic hydroperoxides, and expression of ohr is often regulated by a MarR-type regulator called OhrR. The genes annotated as BAB2_0350 and BAB2_0351 in the Brucella abortus 2308 genome sequence are predicted to encode OhrR and Ohr orthologs, respectively. Using isogenic ohr and ohrR mutants and lacZ promoter fusions, it was determined that Ohr contributes to resistance to organic hydroperoxide, but not hydrogen peroxide, in B. abortus 2308 and that OhrR represses the transcription of both ohr and ohrR in this strain. Moreover, electrophoretic mobility shift assays and DNase I footprinting revealed that OhrR binds directly to a specific region in the intergenic region between ohr and ohrR that shares extensive nucleotide sequence similarity with so-called "OhrR boxes" described in other bacteria. While Ohr plays a prominent role in protecting B. abortus 2308 from organic hydroperoxide stress in in vitro assays, this protein is not required for the wild-type virulence of this strain in cultured murine macrophages or experimentally infected mice. | 2012 | 22821968 |
| 556 | 4 | 0.8908 | An ArsR/SmtB family member regulates arsenic resistance genes unusually arranged in Thermus thermophilus HB27. Arsenic resistance is commonly clustered in ars operons in bacteria; main ars operon components encode an arsenate reductase, a membrane extrusion protein, and an As-sensitive transcription factor. In the As-resistant thermophile Thermus thermophilus HB27, genes encoding homologues of these proteins are interspersed in the chromosome. In this article, we show that two adjacent genes, TtsmtB, encoding an ArsR/SmtB transcriptional repressor and, TTC0354, encoding a Zn(2+) /Cd(2+) -dependent membrane ATPase are involved in As resistance; differently from characterized ars operons, the two genes are transcribed from dedicated promoters upstream of their respective genes, whose expression is differentially regulated at transcriptional level. Mutants defective in TtsmtB or TTC0354 are more sensitive to As than the wild type, proving their role in arsenic resistance. Recombinant dimeric TtSmtB binds in vitro to both promoters, but its binding capability decreases upon interaction with arsenate and, less efficiently, with arsenite. In vivo and in vitro experiments also demonstrate that the arsenate reductase (TtArsC) is subjected to regulation by TtSmtB. We propose a model for the regulation of As resistance in T. thermophilus in which TtSmtB is the arsenate sensor responsible for the induction of TtArsC which generates arsenite exported by TTC0354 efflux protein to detoxify cells. | 2017 | 28696001 |
| 546 | 5 | 0.8907 | Resistance to organic hydroperoxides requires ohr and ohrR genes in Sinorhizobium meliloti. BACKGROUND: Sinorhizobium meliloti is a symbiotic nitrogen-fixing bacterium that elicits nodules on roots of host plants Medicago sativa. During nodule formation bacteria have to withstand oxygen radicals produced by the plant. Resistance to H2O2 and superoxides has been extensively studied in S. meliloti. In contrast resistance to organic peroxides has not been investigated while S. meliloti genome encodes putative organic peroxidases. Organic peroxides are produced by plants and are highly toxic. The resistance to these oxygen radicals has been studied in various bacteria but never in plant nodulating bacteria. RESULTS: In this study we report the characterisation of organic hydroperoxide resistance gene ohr and its regulator ohrR in S. meliloti. The inactivation of ohr affects resistance to cumene and ter-butyl hydroperoxides but not to hydrogen peroxide or menadione in vitro. The expression of ohr and ohrR genes is specifically induced by organic peroxides. OhrR binds to the intergenic region between the divergent genes ohr and ohrR. Two binding sites were characterised. Binding to the operator is prevented by OhrR oxidation that promotes OhrR dimerisation. The inactivation of ohr did not affect symbiosis and nitrogen fixation, suggesting that redundant enzymatic activity exists in this strain. Both ohr and ohrR are expressed in nodules suggesting that they play a role during nitrogen fixation. CONCLUSIONS: This report demonstrates the significant role Ohr and OhrR proteins play in bacterial stress resistance against organic peroxides in S. meliloti. The ohr and ohrR genes are expressed in nodule-inhabiting bacteroids suggesting a role during nodulation. | 2011 | 21569462 |
| 115 | 6 | 0.8895 | Genome mining reveals uncommon alkylpyrones as type III PKS products from myxobacteria. Type III polyketide synthases (PKSs) are comparatively small homodimeric enzymes affording natural products with diverse structures and functions. While type III PKS biosynthetic pathways have been studied thoroughly in plants, their counterparts from bacteria and fungi are to date scarcely characterized. This gap is exemplified by myxobacteria from which no type III PKS-derived small molecule has previously been isolated. In this study, we conducted a genomic survey of myxobacterial type III PKSs and report the identification of uncommon alkylpyrones as the products of type III PKS biosynthesis from the myxobacterial model strain Myxococcus xanthus DK1622 through a self-resistance-guided screening approach focusing on genes encoding pentapetide repeat proteins, proficient to confer resistance to topoisomerase inhibitors. Using promoter-induced gene expression in the native host as well as heterologous expression of biosynthetic type III PKS genes, sufficient amounts of material could be obtained for structural elucidation and bioactivity testing, revealing potent topoisomerase activity in vitro. | 2019 | 30506464 |
| 579 | 7 | 0.8894 | Control of expression of a periplasmic nickel efflux pump by periplasmic nickel concentrations. There is accumulating evidence that transenvelope efflux pumps of the resistance, nodulation, cell division protein family (RND) are excreting toxic substances from the periplasm across the outer membrane directly to the outside. This would mean that resistance of Gram-negative bacteria to organic toxins and heavy metals is in fact a two-step process: one set of resistance factors control the concentration of a toxic substance in the periplasm, another one that in the cytoplasm. Efficient periplasmic detoxification requires periplasmic toxin sensing and transduction of this signal into the cytoplasm to control expression of the periplasmic detoxification system. Such a signal transduction system was analyzed using the Cnr nickel resistance system from Cupriavidus (Wautersia, Ralstonia, Alcaligenes) metallidurans strain CH34. Resistance is based on nickel efflux mediated by the CnrCBA efflux pump encoded by the cnrYHXCBAT metal resistance determinant. The products of the three genes cnrYXH transcriptionally regulate expression of cnr. CnrY and CnrX are membrane-bound proteins probably functioning as anti sigma factors while CnrH is a cnr-specific extracytoplasmic functions (ECF) sigma factors. Experimental data provided here indicate a signal transduction chain leading from nickel in the periplasm to transcription initiation at the cnr promoters cnrYp and cnrCp, which control synthesis of the nickel efflux pump CnrCBA. | 2005 | 16158236 |
| 345 | 8 | 0.8890 | Genetic redundancy, proximity, and functionality of lspA, the target of antibiotic TA, in the Myxococcus xanthus producer strain. We recently showed that type II signal peptidase (SPaseII) encoded by lspA is the target of an antibiotic called TA (myxovirescin), which is made by Myxococcus xanthus. SPaseII cleaves the signal peptide during bacterial lipoprotein processing. Bacteria typically contain one lspA gene; however, strikingly, the M. xanthus DK1622 genome contains four (lspA1 to lspA4). Since two of these genes, lspA3 and lspA4, are located in the giant TA biosynthetic gene cluster, we hypothesized they may play a role in TA resistance. To investigate the functions of the four M. xanthus lspA (lspA(Mx)) genes, we conducted sequence comparisons and found that they contained nearly all the conserved residues characteristic of SPaseII family members. Genetic studies found that an Escherichia coli ΔlspA mutation could be complemented by any of the lspA(Mx) genes in an lpp mutant background, but not in an E. coli lpp(+) background. Because Lpp is the most abundant E. coli lipoprotein, these results suggest the M. xanthus proteins do not function as efficiently as the host enzyme. In E. coli, overexpression of each of the LspA(Mx) proteins conferred TA and globomycin resistance, although LspA3 conferred the highest degree of resistance. In M. xanthus, each lspA(Mx) gene could be deleted and was therefore dispensable for growth. However, lspA3 or lspA4 deletion mutants each exhibited a tan phase variation bias, which likely accounts for their reduced-swarming and delayed-development phenotypes. In summary, we propose that all four LspA(Mx) proteins function as SPaseIIs and that LspA3 and LspA4 might also have roles in TA resistance and regulation, respectively. | 2014 | 24391051 |
| 374 | 9 | 0.8890 | Simultaneous detection and removal of organomercurial compounds by using the genetic expression system of an organomercury lyase from the transposon Tn MERI1. Using a newly identified organomercury lyase gene (merB3) expression system from Tn MERI1, the mercury resistance transposon first found in Gram-positive bacteria, a dual-purpose system to detect and remove organomercurial contamination was developed. A plasmid was constructed by fusing the promoterless luxAB genes as bioluminescence reporter genes downstream of the merB3 gene and its operator/promoter region. Another plasmid, encoding mer operon genes from merR1 to merA, was also constructed to generate an expression regulatory protein, MerR1, and a mercury reductase enzyme, MerA. These two plasmids were transformed into Escherichia coli cells to produce a biological system that can detect and remove environmental organomercury contamination. Organomercurial compounds, such as neurotoxic methylmercury at nanomolar levels, were detected using the biomonitoring system within a few minutes and were removed during the next few hours. | 2002 | 12073137 |
| 583 | 10 | 0.8888 | MarR family proteins sense sulfane sulfur in bacteria. Members of the multiple antibiotic resistance regulator (MarR) protein family are ubiquitous in bacteria and play critical roles in regulating cellular metabolism and antibiotic resistance. MarR family proteins function as repressors, and their interactions with modulators induce the expression of controlled genes. The previously characterized modulators are insufficient to explain the activities of certain MarR family proteins. However, recently, several MarR family proteins have been reported to sense sulfane sulfur, including zero-valent sulfur, persulfide (R-SSH), and polysulfide (R-SnH, n ≥ 2). Sulfane sulfur is a common cellular component in bacteria whose levels vary during bacterial growth. The changing levels of sulfane sulfur affect the expression of many MarR-controlled genes. Sulfane sulfur reacts with the cysteine thiols of MarR family proteins, causing the formation of protein thiol persulfide, disulfide bonds, and other modifications. Several MarR family proteins that respond to reactive oxygen species (ROS) also sense sulfane sulfur, as both sulfane sulfur and ROS induce the formation of disulfide bonds. This review focused on MarR family proteins that sense sulfane sulfur. However, the sensing mechanisms reviewed here may also apply to other proteins that detect sulfane sulfur, which is emerging as a modulator of gene regulation. | 2024 | 38948149 |
| 804 | 11 | 0.8888 | Cloning, mutagenesis, and characterization of the microalga Parietochloris incisa acetohydroxyacid synthase, and its possible use as an endogenous selection marker. Parietochloris incisa is an oleaginous fresh water green microalga that accumulates an unusually high content of the valuable long-chain polyunsaturated fatty acid (LC-PUFA) arachidonic acid within triacylglycerols in cytoplasmic lipid bodies. Here, we describe cloning and mutagenesis of the P. incisa acetohydroxyacid synthase (PiAHAS) gene for use as an herbicide resistance selection marker for transformation. Use of an endogenous gene circumvents the risks and regulatory difficulties of cultivating antibiotic-resistant organisms. AHAS is present in plants and microorganisms where it catalyzes the first essential step in the synthesis of branched-chain amino acids. It is the target enzyme of the herbicide sulfometuron methyl (SMM), which effectively inhibits growth of bacteria and plants. Several point mutations of AHAS are known to confer herbicide resistance. We cloned the cDNA that encodes PiAHAS and introduced a W605S point mutation (PimAHAS). Catalytic activity and herbicide resistance of the wild-type and mutant proteins were characterized in the AHAS-deficient E. coli, BUM1 strain. Cloned PiAHAS wild-type and mutant genes complemented AHAS-deficient bacterial growth. Furthermore, bacteria expressing the mutant PiAHAS exhibited high resistance to SMM. Purified PiAHAS wild-type and mutant proteins were assayed for enzymatic activity and herbicide resistance. The W605S mutation was shown to cause a twofold decrease in enzymatic activity and in affinity for the Pyruvate substrate. However, the mutant exhibited 7 orders of magnitude higher resistance to the SMM herbicide than that of the wild type. | 2012 | 22488216 |
| 514 | 12 | 0.8881 | The organoarsenical biocycle and the primordial antibiotic methylarsenite. Arsenic is the most pervasive environmental toxic substance. As a consequence of its ubiquity, nearly every organism has genes for resistance to inorganic arsenic. In bacteria these genes are found largely in bacterial arsenic resistance (ars) operons. Recently a parallel pathway for synthesis and degradation of methylated arsenicals has been identified. The arsM gene product encodes the ArsM (AS3MT in animals) As(iii) S-adenosylmethionine methyltransferase that methylates inorganic trivalent arsenite in three sequential steps to methylarsenite MAs(iii), dimethylarsenite (DMAs(iii) and trimethylarsenite (TMAs(iii)). MAs(iii) is considerably more toxic than As(iii), and we have proposed that MAs(iii) was a primordial antibiotic. Under aerobic conditions these products are oxidized to nontoxic pentavalent arsenicals, so that methylation became a detoxifying pathway after the atmosphere became oxidizing. Other microbes have acquired the ability to regenerate MAs(v) by reduction, transforming it again into toxic MAs(iii). Under this environmental pressure, MAs(iii) resistances evolved, including the arsI, arsH and arsP genes. ArsI is a C-As bond lyase that demethylates MAs(iii) back to less toxic As(iii). ArsH re-oxidizes MAs(iii) to MAs(v). ArsP actively extrudes MAs(iii) from cells. These proteins confer resistance to this primitive antibiotic. This oscillation between MAs(iii) synthesis and detoxification is an essential component of the arsenic biogeocycle. | 2016 | 27730229 |
| 711 | 13 | 0.8879 | Non-specific, general and multiple stress resistance of growth-restricted Bacillus subtilis cells by the expression of the sigmaB regulon. Bacillus subtilis cells respond almost immediately to different stress conditions by increasing the production of general stress proteins (GSPs). The genes encoding the majority of the GSPs that are induced by heat, ethanol, salt stress or by starvation for glucose, oxygen or phosphate belong to the sigmaB-dependent general stress regulon. Despite a good understanding of the complex regulation of the activity of sigmaB and knowledge of a very large number of general stress genes controlled by sigmaB, first insights into the physiological role of this nonspecific stress response have been obtained only very recently. To explore the physiological role of this reguIon, we and others identified sigmaB-dependent general stress genes and compared the stress tolerance of wild-type cells with mutants lacking sigmaB or general stress proteins. The proteins encoded by sigmaB-dependent general stress genes can be divided into at least five functional groups that most probably provide growth-restricted B. subtilis cells with a multiple stress resistance in anticipation of future stress. In particular, sigB mutants are impaired in non-specific resistance to oxidative stress, which requires the sigmaB-dependent dps gene encoding a DNA-protecting protein. Protection against oxidative damage of membranes, proteins or DNA could be the most essential component of sigmaB mediated general stress resistance in growth-arrested aerobic gram-positive bacteria. Other general stress genes have both a sigmaB-dependent induction pathway and a second sigmaB-independent mechanism of stress induction, thereby partially compensating for a sigmaB deficiency in a sigB mutant. In contrast to sigB mutants, null mutations in genes encoding those proteins, such as cIpP or cIpC, cause extreme sensitivity to salt or heat. | 1998 | 9767581 |
| 518 | 14 | 0.8878 | Bacitracin and nisin resistance in Staphylococcus aureus: a novel pathway involving the BraS/BraR two-component system (SA2417/SA2418) and both the BraD/BraE and VraD/VraE ABC transporters. Two-component systems (TCSs) are key regulatory pathways allowing bacteria to adapt their genetic expression to environmental changes. Bacitracin, a cyclic dodecylpeptide antibiotic, binds to undecaprenyl pyrophosphate, the lipid carrier for cell wall precursors, effectively inhibiting peptidoglycan biosynthesis. We have identified a novel and previously uncharacterized TCS in the major human pathogen Staphylococcus aureus that we show to be essential for bacitracin and nisin resistance: the BraS/BraR system (Bacitracin resistance associated; SA2417/SA2418). The braRS genes are located immediately upstream from genes encoding an ABC transporter, accordingly designated BraDE. We have shown that the BraSR/BraDE module is a key bacitracin and nisin resistance determinant in S. aureus. In the presence of low antibiotic concentrations, BraSR activate transcription of two operons encoding ABC transporters: braDE and vraDE. We identified a highly conserved imperfect palindromic sequence upstream from the braDE and vraDE promoter sequences, essential for their transcriptional activation by BraSR, suggesting it is the likely BraR binding site. We demonstrated that the two ABC transporters play distinct and original roles in antibiotic resistance: BraDE is involved in bacitracin sensing and signalling through BraSR, whereas VraDE acts specifically as a detoxification module and is sufficient to confer bacitracin and nisin resistance when produced on its own. We show that these processes require functional BraD and VraD nucleotide-binding domain proteins, and that the large extracellular loop of VraE confers its specificity in bacitracin resistance. This is the first example of a TCS associated with two ABC transporters playing separate roles in signal transduction and antibiotic resistance. | 2011 | 21696458 |
| 802 | 15 | 0.8878 | YqhC regulates transcription of the adjacent Escherichia coli genes yqhD and dkgA that are involved in furfural tolerance. Previous results have demonstrated that the silencing of adjacent genes encoding NADPH-dependent furfural oxidoreductases (yqhD dkgA) is responsible for increased furfural tolerance in an E. coli strain EMFR9 [Miller et al., Appl Environ Microbiol 75:4315-4323, 2009]. This gene silencing is now reported to result from the spontaneous insertion of an IS10 into the coding region of yqhC, an upstream gene. YqhC shares homology with transcriptional regulators belonging to the AraC/XylS family and was shown to act as a positive regulator of the adjacent operon encoding YqhD and DkgA. Regulation was demonstrated by constructing a chromosomal deletion of yqhC, a firefly luciferase reporter plasmid for yqhC, and by a direct comparison of furfural resistance and NADPH-dependent furfural reductase activity. Closely related bacteria contain yqhC, yqhD, and dkgA orthologs in the same arrangement as in E. coli LY180. Orthologs of yqhC are also present in more distantly related Gram-negative bacteria. Disruption of yqhC offers a useful approach to increase furfural tolerance in bacteria. | 2011 | 20676725 |
| 746 | 16 | 0.8878 | Novel antimicrobial 3-phenyl-4-phenoxypyrazole derivatives target cell wall lipid intermediates with low mammalian cytotoxicity. The growing crisis of antimicrobial resistance (AMR) underscores the critical need for innovative antimicrobial discoveries. Novel antibiotics targeting the bacterial cell wall remain an attractive area of research, due to their conservation and essentiality in bacteria and their absence in eukaryotic cells. Antibiotics targeting lipid II are of special interest due to the reduced potential for target modification of lipid components and their surface accessibility to inhibitors. In this study, we identified 3-phenyl-4-phenoxypyrazole analogues named PYO12 and PYO12a with bactericidal activity against gram-positive bacteria and low cytotoxicity for different types of mammalian cells. Gram-negative bacteria were resistant to PYO12 activity through extrusion of this compound via efflux pumps. Exposure to PYO12 induces expression of genes involved in resistance to antimicrobials targeting the cell wall, suggesting that PYO12 acts via binding to lipid II or other lipid intermediates involved in peptidoglycan or teichoic acid biosynthesis. Antagonism of PYO12 antibacterial activity by undecaprenyl-pyrophosphate supports the idea that PYO12 may bind to the lipid moiety of lipid II blocking the shuttling of peptidoglycan precursors across the cytoplasmic membrane. These findings open opportunities to further develop these compounds as antibiotics targeting bacterial cell wall synthesis. | 2025 | 41083642 |
| 549 | 17 | 0.8878 | Extracytoplasmic function sigma factor σ(D) confers resistance to environmental stress by enhancing mycolate synthesis and modifying peptidoglycan structures in Corynebacterium glutamicum. Mycolates are α-branched, β-hydroxylated, long-chain fatty acid specifically synthesized in bacteria in the suborder Corynebacterineae of the phylum Actinobacteria. They form an outer membrane, which functions as a permeability barrier and confers pathogenic mycobacteria to resistance to antibiotics. Although the mycolate biosynthetic pathway has been intensively studied, knowledge of transcriptional regulation of genes involved in this pathway is limited. Here, we report that the extracytoplasmic function sigma factor σ(D) is a key regulator of the mycolate synthetic genes in Corynebacterium glutamicum in the suborder. Chromatin immunoprecipitation with microarray analysis detected σ(D) -binding regions in the genome, establishing a consensus promoter sequence for σ(D) recognition. The σ(D) regulon comprised acyl-CoA carboxylase subunits, acyl-AMP ligase, polyketide synthase and mycolyltransferases; they were involved in mycolate synthesis. Indeed, deletion or overexpression of sigD encoding σ(D) modified the extractable mycolate amount. Immediately downstream of sigD, rsdA encoded anti-σ(D) and was under the control of a σ(D) -dependent promoter. Another σ(D) regulon member, l,d-transpeptidase, conferred lysozyme resistance. Thus, σ(D) modifies peptidoglycan cross-linking and enhances mycolate synthesis to provide resistance to environmental stress. | 2018 | 29148103 |
| 582 | 18 | 0.8877 | Sulfane Sulfur Is a Strong Inducer of the Multiple Antibiotic Resistance Regulator MarR in Escherichia coli. Sulfane sulfur, including persulfide and polysulfide, is produced from the metabolism of sulfur-containing organic compounds or from sulfide oxidation. It is a normal cellular component, participating in signaling. In bacteria, it modifies gene regulators to activate the expression of genes involved in sulfur metabolism. However, to determine whether sulfane sulfur is a common signal in bacteria, additional evidence is required. The ubiquitous multiple antibiotic resistance regulator (MarR) family of regulators controls the expression of numerous genes, but the intrinsic inducers are often elusive. Recently, two MarR family members, Pseudomonas aeruginosa MexR and Staphylococcus aureus MgrA, have been reported to sense sulfane sulfur. Here, we report that Escherichia coli MarR, the prototypical member of the family, also senses sulfane sulfur to form one or two disulfide or trisulfide bonds between two dimers. Although the tetramer with two disulfide bonds does not bind to its target DNA, our results suggest that the tetramer with one disulfide bond does bind to its target DNA, with reduced affinity. An MarR-repressed mKate reporter is strongly induced by polysulfide in E. coli. Further investigation is needed to determine whether sulfane sulfur is a common signal of the family members, but three members sense cellular sulfane sulfur to turn on antibiotic resistance genes. The findings offer additional support for a general signaling role of sulfane sulfur in bacteria. | 2021 | 34829649 |
| 558 | 19 | 0.8876 | Thiamine pyrophosphate riboswitches are targets for the antimicrobial compound pyrithiamine. Thiamine metabolism genes are regulated in numerous bacteria by a riboswitch class that binds the coenzyme thiamine pyrophosphate (TPP). We demonstrate that the antimicrobial action of the thiamine analog pyrithiamine (PT) is mediated by interaction with TPP riboswitches in bacteria and fungi. For example, pyrithiamine pyrophosphate (PTPP) binds the TPP riboswitch controlling the tenA operon in Bacillus subtilis. Expression of a TPP riboswitch-regulated reporter gene is reduced in transgenic B. subtilis or Escherichia coli when grown in the presence of thiamine or PT, while mutant riboswitches in these organisms are unresponsive to these ligands. Bacteria selected for PT resistance bear specific mutations that disrupt ligand binding to TPP riboswitches and derepress certain TPP metabolic genes. Our findings demonstrate that riboswitches can serve as antimicrobial drug targets and expand our understanding of thiamine metabolism in bacteria. | 2005 | 16356850 |