# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 462 | 0 | 0.9314 | Discovery and characterization of genes conferring natural resistance to the antituberculosis antibiotic capreomycin. Metagenomic-based studies have predicted an extraordinary number of potential antibiotic-resistance genes (ARGs). These ARGs are hidden in various environmental bacteria and may become a latent crisis for antibiotic therapy via horizontal gene transfer. In this study, we focus on a resistance gene cph, which encodes a phosphotransferase (Cph) that confers resistance to the antituberculosis drug capreomycin (CMN). Sequence Similarity Network (SSN) analysis classified 353 Cph homologues into five major clusters, where the proteins in cluster I were found in a broad range of actinobacteria. We examine the function and antibiotics targeted by three putative resistance proteins in cluster I via biochemical and protein structural analysis. Our findings reveal that these three proteins in cluster I confer resistance to CMN, highlighting an important aspect of CMN resistance within this gene family. This study contributes towards understanding the sequence-structure-function relationships of the phosphorylation resistance genes that confer resistance to CMN. | 2023 | 38114770 |
| 229 | 1 | 0.9283 | Molecular basis underlying Mycobacterium tuberculosis D-cycloserine resistance. Is there a role for ubiquinone and menaquinone metabolic pathways? INTRODUCTION: Tuberculosis remains a formidable threat to global public health. Multidrug-resistant tuberculosis presents increasing burden on the control strategy. D-Cycloserine (DCS) is an effective second-line drug against Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis. Though less potent than isoniazid (INH) and streptomycin, DCS is crucial for antibiotic-resistant tuberculosis. One advantage of DCS is that less drug-resistant M. tuberculosis is reported in comparison with first-line antituberculosis drugs such as INH and rifampin. AREAS COVERED: In this review, we summarise our current knowledge of DCS, and review the drug target and low-level resistance of DCS in M. tuberculosis. We summarise the metabolism of D-alanine (D-Ala) and peptidoglycan biosynthesis in bacteria. We first compared the amino acid similarity of Mycobacterium alanine racemase and D-Ala:D-alanine ligase and quite unexpectedly found that the two enzymes are highly conserved among Mycobacterium. EXPERT OPINION: We summarise the drug targets of DCS and possible mechanisms underlying its low-level resistance for the first time. One significant finding is that ubiquinone and menaquinone metabolism-related genes are novel genes underlying DCS resistance in Escherichia coli and with homologues in M. tuberculosis. Further understanding of DCS targets and basis for its low-level resistance might inspire us to improve the use of DCS or find better drug targets. | 2014 | 24773568 |
| 9991 | 2 | 0.9272 | A bifunctional dihydrofolate synthetase--folylpolyglutamate synthetase in Plasmodium falciparum identified by functional complementation in yeast and bacteria. Folate metabolism in the human malaria parasite Plasmodium falciparum is an essential activity for cell growth and replication, and the target of an important class of therapeutic agents in widespread use. However, resistance to antifolate drugs is a major health problem in the developing world. To date, only two activities in this complex pathway have been targeted by antimalarials. To more fully understand the mechanisms of antifolate resistance and to identify promising targets for new chemotherapies, we have cloned genes encoding as yet uncharacterised enzymes in this pathway. By means of complementation experiments using 1-carbon metabolism mutants of both Escherichia coli and Saccharomyces cerevisiae, we demonstrate here that one of these parasite genes encodes both dihydrofolate synthetase (DHFS) and folylpolyglutamate synthetase (FPGS) activities, which catalyse the synthesis and polyglutamation of folate derivatives, respectively. The malaria parasite is the first known example of a eukaryote encoding both DHFS and FPGS activities in a single gene. DNA sequencing of this gene in antifolate-resistant strains of P. falciparum, as well as drug-inhibition assays performed on yeast and bacteria expressing PfDHFS--FPGS, indicate that current antifolate regimes do not target this enzyme. As PfDHFS--FPGS harbours two activities critical to folate metabolism, one of which has no human counterpart, this gene product offers a novel chemotherapeutic target with the potential to deliver a powerful blockage to parasite growth. | 2001 | 11223131 |
| 331 | 3 | 0.9261 | MmpS4 promotes glycopeptidolipids biosynthesis and export in Mycobacterium smegmatis. The MmpS family (mycobacterial membrane protein small) includes over 100 small membrane proteins specific to the genus Mycobacterium that have not yet been studied experimentally. The genes encoding MmpS proteins are often associated with mmpL genes, which are homologous to the RND (resistance nodulation cell division) genes of Gram-negative bacteria that encode proteins functioning as multidrug efflux system. We showed by molecular genetics and biochemical analysis that MmpS4 in Mycobacterium smegmatis is required for the production and export of large amounts of cell surface glycolipids, but is dispensable for biosynthesis per se. A new specific and sensitive method utilizing single-chain antibodies against the surface-exposed glycolipids was developed to confirm that MmpS4 was dispensable for transport to the surface. Orthologous complementation demonstrated that the MmpS4 proteins are exchangeable, thus not specific to a defined lipid species. MmpS4 function requires the formation of a protein complex at the pole of the bacillus, which requires the extracytosolic C-terminal domain of MmpS4. We suggest that MmpS proteins facilitate lipid biosynthesis by acting as a scaffold for coupled biosynthesis and transport machinery. | 2010 | 21062372 |
| 8159 | 4 | 0.9257 | Quaternary Ammonium Salts: Insights into Synthesis and New Directions in Antibacterial Applications. The overuse of antibiotics has led to the emergence of a large number of antibiotic-resistant genes in bacteria, and increasing evidence indicates that a fungicide with an antibacterial mechanism different from that of antibiotics is needed. Quaternary ammonium salts (QASs) are a biparental substance with good antibacterial properties that kills bacteria through simple electrostatic adsorption and insertion into cell membranes/altering of cell membrane permeability. Therefore, the probability of bacteria developing drug resistance is greatly reduced. In this review, we focus on the synthesis and application of single-chain QASs, double-chain QASs, heterocyclic QASs, and gemini QASs (GQASs). Some possible structure-function relationships of QASs are also summarized. As such, we hope this review will provide insight for researchers to explore more applications of QASs in the field of antimicrobials with the aim of developing systems for clinical applications. | 2023 | 36748912 |
| 9990 | 5 | 0.9253 | Axe-Txe, a broad-spectrum proteic toxin-antitoxin system specified by a multidrug-resistant, clinical isolate of Enterococcus faecium. Enterococcal species of bacteria are now acknowledged as leading causes of bacteraemia and other serious nosocomial infections. However, surprisingly little is known about the molecular mechanisms that promote the segregational stability of antibiotic resistance and other plasmids in these bacteria. Plasmid pRUM (24 873 bp) is a multidrug resistance plasmid identified in a clinical isolate of Enterococcus faecium. A novel proteic-based toxin-antitoxin cassette identified on pRUM was demonstrated to be a functional segregational stability module in both its native host and evolutionarily diverse bacterial species. Induced expression of the toxin protein (Txe) of this system resulted in growth inhibition in Escherichia coli. The toxic effect of Txe was alleviated by co-expression of the antitoxin protein, Axe. Homologues of the axe and txe genes are present in the genomes of a diversity of Eubacteria. These homologues (yefM-yoeB) present in the E. coli chromosome function as a toxin-antitoxin mechanism, although the Axe and YefM antitoxin components demonstrate specificity for their cognate toxin proteins in vivo. Axe-Txe is one of the first functional proteic toxin-antitoxin systems to be accurately described for Gram-positive bacteria. | 2003 | 12603745 |
| 9222 | 6 | 0.9253 | Bacterial proton motive force as an unprecedented target to control antimicrobial resistance. Novel antibacterial therapies are urgently required to tackle the increasing number of multidrug-resistant pathogens. Identification of new antimicrobial targets is critical to avoid possible cross-resistance issues. Bacterial proton motive force (PMF), an energetic pathway located on the bacterial membrane, crucially regulates various biological possesses such as adenosine triphosphate synthesis, active transport of molecules, and rotation of bacterial flagella. Nevertheless, the potential of bacterial PMF as an antibacterial target remains largely unexplored. The PMF generally comprises electric potential (ΔΨ) and transmembrane proton gradient (ΔpH). In this review, we present an overview of bacterial PMF, including its functions and characterizations, highlighting the representative antimicrobial agents that specifically target either ΔΨ or ΔpH. At the same time, we also discuss the adjuvant potential of bacterial PMF-targeting compounds. Lastly, we highlight the value of PMF disruptors in preventing the transmission of antibiotic resistance genes. These findings suggest that bacterial PMF represents an unprecedented target, providing a comprehensive approach to controlling antimicrobial resistance. | 2023 | 36896761 |
| 558 | 7 | 0.9251 | 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 |
| 760 | 8 | 0.9247 | The underling mechanism of bacterial TetR/AcrR family transcriptional repressors. Bacteria transcriptional regulators are classified by their functional and sequence similarities. Member of the TetR/AcrR family is two-domain proteins including an N-terminal HTH DNA-binding motif and a C-terminal ligand recognition domain. The C-terminal ligand recognition domain can recognize the very same compounds as their target transporters transferred. TetRs act as chemical sensors to monitor both the cellular environmental dynamics and their regulated genes underlying many events, such as antibiotics production, osmotic stress, efflux pumps, multidrug resistance, metabolic modulation, and pathogenesis. Compounds targeting Mycobacterium tuberculosis ethR represent promising novel antibiotic potentiater. TetR-mediated multidrug efflux pumps regulation might be good target candidate for the discovery of better new antibiotics against drug resistance. | 2013 | 23602932 |
| 527 | 9 | 0.9243 | Characterization of the bagremycin biosynthetic gene cluster in Streptomyces sp. Tü 4128. Bagremycin A and bagremycin B isolated from Streptomyces sp. Tü 4128 have activities against Gram-positive bacteria, fungi and also have a weak antitumor activity, which make them have great potential for development of novel antibiotics. Here, we report a draft genome 8,424,112 bp in length of S. sp. Tü 4128 by Illumina Hiseq2000, and identify the bagremycins biosynthetic gene cluster (BGC) by bioinformatics analysis. The putative bagremycins BGC includes 16 open reading frames (ORFs) with the functions of biosynthesis, resistance and regulation. Disruptions of relative genes and HPLC analysis of bagremycins production demonstrated that not all the genes within the BGC are responsible for the biosynthesis of bagremycins. In addition, the biosynthetic pathways of bagremycins are proposed for deeper inquiries into their intriguing biosynthetic mechanism. | 2019 | 30526412 |
| 8158 | 10 | 0.9242 | Nanobioconjugates: Weapons against Antibacterial Resistance. The increase in drug resistance in pathogenic bacteria is emerging as a global threat as we swiftly edge toward the postantibiotic era. Nanobioconjugates have gained tremendous attention to treat multidrug-resistant (MDR) bacteria and biofilms due to their tunable physicochemical properties, drug targeting ability, enhanced uptake, and alternate mechanisms of drug action. In this review, we highlight the recent advances made in the use of nanobioconjugates to combat antibacterial resistance and provide crucial insights for designing nanomaterials that can serve as antibacterial agents for nanotherapeutics, nanocargos for targeted antibiotic delivery, or both. Also discussed are different strategies for treating robust biofilms formed by bacteria. | 2020 | 35019602 |
| 654 | 11 | 0.9242 | Conjugation inhibitors compete with palmitic acid for binding to the conjugative traffic ATPase TrwD, providing a mechanism to inhibit bacterial conjugation. Bacterial conjugation is a key mechanism by which bacteria acquire antibiotic resistance. Therefore, conjugation inhibitors (COINs) are promising compounds in the fight against the spread of antibiotic resistance genes among bacteria. Unsaturated fatty acids (uFAs) and alkynoic fatty acid derivatives, such as 2-hexadecanoic acid (2-HDA), have been reported previously as being effective COINs. The traffic ATPase TrwD, a VirB11 homolog in plasmid R388, is the molecular target of these compounds, which likely affect binding of TrwD to bacterial membranes. In this work, we demonstrate that COINs are abundantly incorporated into Escherichia coli membranes, replacing palmitic acid as the major component of the membrane. We also show that TrwD binds palmitic acid, thus facilitating its interaction with the membrane. Our findings also suggest that COINs bind TrwD at a site that is otherwise occupied by palmitic acid. Accordingly, molecular docking predictions with palmitic acid indicated that it shares the same binding site as uFAs and 2-HDA, although it differs in the contacts involved in this interaction. We also identified 2-bromopalmitic acid, a palmitate analog that inhibits many membrane-associated enzymes, as a compound that effectively reduces TrwD ATPase activity and bacterial conjugation. Moreover, we demonstrate that 2-bromopalmitic and palmitic acids both compete for the same binding site in TrwD. Altogether, these detailed findings open up a new avenue in the search for effective synthetic inhibitors of bacterial conjugation, which may be pivotal for combating multidrug-resistant bacteria. | 2018 | 30201608 |
| 8433 | 12 | 0.9242 | Thermoresponsive Nanostructures: From Mechano-Bactericidal Action to Bacteria Release. Overuse of antibiotics can increase the risk of notorious antibiotic resistance in bacteria, which has become a growing public health concern worldwide. Featured with the merit of mechanical rupture of bacterial cells, the bioinspired nanopillars are promising alternatives to antibiotics for combating bacterial infections while avoiding antibacterial resistance. However, the resident dead bacterial cells on nanopillars may greatly impair their bactericidal capability and ultimately impede their translational potential toward long-term applications. Here, we show that the functions of bactericidal nanopillars can be significantly broadened by developing a hybrid thermoresponsive polymer@nanopillar-structured surface, which retains all of the attributes of pristine nanopillars and adds one more: releasing dead bacteria. We fabricate this surface through coaxially decorating mechano-bactericidal ZnO nanopillars with thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) brushes. Combining the benefits of ZnO nanopillars and PNIPAAm chains, the antibacterial performances can be controllably regulated between ultrarobust mechano-bactericidal action (∼99%) and remarkable bacteria-releasing efficiency (∼98%). Notably, both the mechanical sterilization against the live bacteria and the controllable release for the pinned dead bacteria solely stem from physical actions, stimulating the exploration of intelligent structure-based bactericidal surfaces with persistent antibacterial properties without the risk of triggering drug resistance. | 2021 | 34905683 |
| 8599 | 13 | 0.9241 | Artificial sweeteners stimulate horizontal transfer of extracellular antibiotic resistance genes through natural transformation. Antimicrobial resistance has emerged as a global threat to human health. Natural transformation is an important pathway for horizontal gene transfer, which facilitates the dissemination of antibiotic resistance genes (ARGs) among bacteria. Although it is suspected that artificial sweeteners could exert antimicrobial effects, little is known whether artificial sweeteners would also affect horizontal transfer of ARGs via transformation. Here we demonstrate that four commonly used artificial sweeteners (saccharin, sucralose, aspartame, and acesulfame potassium) promote transfer of ARGs via natural transformation in Acinetobacter baylyi ADP1, a model organism for studying competence and transformation. Such phenomenon was also found in a Gram-positive human pathogen Bacillus subtilis and mice faecal microbiome. We reveal that exposure to these sweeteners increases cell envelope permeability and results in an upregulation of genes encoding DNA uptake and translocation (Com) machinery. In addition, we find that artificial sweeteners induce an increase in plasmid persistence in transformants. We propose a mathematical model established to predict the long-term effects on transformation dynamics under exposure to these sweeteners. Collectively, our findings offer insights into natural transformation promoted by artificial sweeteners and highlight the need to evaluate these environmental contaminants for their antibiotic-like side effects. | 2022 | 34465899 |
| 9085 | 14 | 0.9240 | Mode of action and resistance studies unveil new roles for tropodithietic acid as an anticancer agent and the γ-glutamyl cycle as a proton sink. While we have come to appreciate the architectural complexity of microbially synthesized secondary metabolites, far less attention has been paid to linking their structural features with possible modes of action. This is certainly the case with tropodithietic acid (TDA), a broad-spectrum antibiotic generated by marine bacteria that engage in dynamic symbioses with microscopic algae. TDA promotes algal health by killing unwanted marine pathogens; however, its mode of action (MoA) and significance for the survival of an algal-bacterial miniecosystem remains unknown. Using cytological profiling, we herein determine the MoA of TDA and surprisingly find that it acts by a mechanism similar to polyether antibiotics, which are structurally highly divergent. We show that like polyether drugs, TDA collapses the proton motive force by a proton antiport mechanism, in which extracellular protons are exchanged for cytoplasmic cations. The α-carboxy-tropone substructure is ideal for this purpose as the proton can be carried on the carboxyl group, whereas the basicity of the tropylium ion facilitates cation export. Based on similarities to polyether anticancer agents we have further examined TDA's cytotoxicity and find it to exhibit potent, broad-spectrum anticancer activities. These results highlight the power of MoA-profiling technologies in repurposing old drugs for new targets. In addition, we identify an operon that confers TDA resistance to the producing marine bacteria. Bioinformatic and biochemical analyses of these genes lead to a previously unknown metabolic link between TDA/acid resistance and the γ-glutamyl cycle. The implications of this resistance mechanism in the context of the algal-bacterial symbiosis are discussed. | 2016 | 26802120 |
| 8156 | 15 | 0.9240 | Innovative Delivery System Combining CRISPR-Cas12f for Combatting Antimicrobial Resistance in Gram-Negative Bacteria. Antimicrobial resistance poses a significant global challenge, demanding innovative approaches, such as the CRISPR-Cas-mediated resistance plasmid or gene-curing system, to effectively combat this urgent crisis. To enable successful curing of antimicrobial genes or plasmids through CRISPR-Cas technology, the development of an efficient broad-host-range delivery system is paramount. In this study, we have successfully designed and constructed a novel functional gene delivery plasmid, pQ-mini, utilizing the backbone of a broad-host-range Inc.Q plasmid. Moreover, we have integrated the CRISPR-Cas12f system into the pQ-mini plasmid to enable gene-curing in broad-host of bacteria. Our findings demonstrate that pQ-mini facilitates the highly efficient transfer of genetic elements to diverse bacteria, particularly in various species in the order of Enterobacterales, exhibiting a broader host range and superior conjugation efficiency compared to the commonly used pMB1-like plasmid. Notably, pQ-mini effectively delivers the CRISPR-Cas12f system to antimicrobial-resistant strains, resulting in remarkable curing efficiencies for plasmid-borne mcr-1 or bla(KPC) genes that are comparable to those achieved by the previously reported pCasCure system. In conclusion, our study successfully establishes and optimizes pQ-mini as a broad-host-range functional gene delivery vector. Furthermore, in combination with the CRISPR-Cas system, pQ-mini demonstrates its potential for broad-host delivery, highlighting its promising role as a novel antimicrobial tool against the growing threat of antimicrobial resistance. | 2024 | 38863339 |
| 500 | 16 | 0.9240 | An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea. Erythromycin A, a clinically important polyketide antibiotic, is produced by the Gram-positive bacterium Saccharopolyspora erythraea. In an arrangement that seems to be generally true of antibiotic biosynthetic genes in Streptomyces and related bacteria like S. erythraea, the ery genes encoding the biosynthetic pathway to erythromycin are clustered around the gene (ermE) that confers self-resistance on S. erythraea. The aglycone core of erythromycin A is derived from one propionyl-CoA and six methylmalonyl-CoA units, which are incorporated head-to-tail into the growing polyketide chain, in a process similar to that of fatty-acid biosynthesis, to generate a macrolide intermediate, 6-deoxyerythronolide B. 6-Deoxyerythronolide B is converted into erythromycin A through the action of specific hydroxylases, glycosyltransferases and a methyltransferase. We report here the analysis of about 10 kilobases of DNA from S. erythraea, cloned by chromosome 'walking' outwards from the erythromycin-resistance determinant ermE, and previously shown to be essential for erythromycin biosynthesis. Partial sequencing of this region indicates that it encodes the synthase. Our results confirm this, and reveal a novel organization of the erythromycin-producing polyketide synthase, which provides further insight into the mechanism of chain assembly. | 1990 | 2234082 |
| 343 | 17 | 0.9240 | Cloning and molecular characterization of three arylamine N-acetyltransferase genes from Bacillus anthracis: identification of unusual enzymatic properties and their contribution to sulfamethoxazole resistance. The arylamine N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes that catalyze the N-acetylation of arylamines and their N-hydroxylated metabolites. These enzymes play a key role in detoxication of numerous drugs and xenobiotics. We report here the cloning, functional expression, and characterization of three new NAT genes (termed banatA, banatB, and banatC) from the pathogen Bacillus anthracis. The sequences of the corresponding proteins are approximately 30% identical with those of characterized eukaryotic and prokaryotic NAT enzymes, and the proteins were recognized by an anti-NAT antibody. The three genes were endogenously expressed in B. anthracis, and NAT activity was found in cell extracts. The three NAT homologues exhibited distinct structural and enzymatic properties, some of which have not previously been observed with other NAT enzymes. Recombinant BanatC displayed strong NAT activity toward several prototypic NAT substrates, including the sulfonamide antibiotic sulfamethoxazole (SMX). As opposed to BanatC, BanatB also had acetyl-CoA (AcCoA) and p-nitrophenyl acetate (PNPA) hydrolysis activity in the absence of arylamine substrates, indicating that it may act as an AcCoA hydrolase. BanatA was devoid of NAT or AcCoA/PNPA hydrolysis activities, suggesting that it may be a new bacterial NAT-like protein with unknown function. Expression of BanatC in Escherichia coli afforded higher-than-normal resistance to SMX in the recombinant bacteria, whereas an inactive mutant of the enzyme did not. These data indicate that BanatC could contribute to the resistance of B. anthracis to SMX. | 2007 | 17511472 |
| 8421 | 18 | 0.9239 | Dynamic stepwise opening of integron attC DNA hairpins by SSB prevents toxicity and ensures functionality. Biologically functional DNA hairpins are found in archaea, prokaryotes and eukaryotes, playing essential roles in various DNA transactions. However, during DNA replication, hairpin formation can stall the polymerase and is therefore prevented by the single-stranded DNA binding protein (SSB). Here, we address the question how hairpins maintain their functional secondary structure despite SSB's presence. As a model hairpin, we used the recombinogenic form of the attC site, essential for capturing antibiotic-resistance genes in the integrons of bacteria. We found that attC hairpins have a conserved high GC-content near their apical loop that creates a dynamic equilibrium between attC fully opened by SSB and a partially structured attC-6-SSB complex. This complex is recognized by the recombinase IntI, which extrudes the hairpin upon binding while displacing SSB. We anticipate that this intriguing regulation mechanism using a base pair distribution to balance hairpin structure formation and genetic stability is key to the dissemination of antibiotic resistance genes among bacteria and might be conserved among other functional hairpins. | 2017 | 28985409 |
| 549 | 19 | 0.9239 | 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 |