# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 328 | 0 | 1.0000 | Multiresistance genes of Rhizobium etli CFN42. Multidrug efflux pumps of bacteria are involved in the resistance to various antibiotics and toxic compounds. In Rhizobium etli, a mutualistic symbiont of Phaseolus vulgaris (bean), genes resembling multidrug efflux pump genes were identified and designated rmrA and rmrB. rmrA was obtained after the screening of transposon-generated fusions that are inducible by bean-root released flavonoids. The predicted gene products of rmrAB shared significant homology to membrane fusion and major facilitator proteins, respectively. Mutants of rmrA formed on average 40% less nodules in bean, while mutants of rmrA and rmrB had enhanced sensitivity to phytoalexins, flavonoids, and salicylic acid, compared with the wild-type strain. Multidrug resistance genes emrAB from Escherichia coli complemented an rmrA mutant from R. etli for resistance to high concentrations of naringenin. | 2000 | 10796024 |
| 591 | 1 | 0.9974 | Muramyl Endopeptidase Spr Contributes to Intrinsic Vancomycin Resistance in Salmonella enterica Serovar Typhimurium. The impermeability barrier provided by the outer membrane of enteric bacteria, a feature lacking in Gram-positive bacteria, plays a major role in maintaining resistance to numerous antimicrobial compounds and antibiotics. Here we demonstrate that mutational inactivation of spr, coding for a muramyl endopeptidase, significantly sensitizes Salmonella enterica serovar Typhimurium to vancomycin without any accompanying apparent growth defect or outer membrane destabilization. A similar phenotype was not achieved by deleting the genes coding for muramyl endopeptidases MepA, PbpG, NlpC, YedA, or YhdO. The spr mutant showed increased autolytic behavior in response to not only vancomycin, but also to penicillin G, an antibiotic for which the mutant displayed a wild-type MIC. A screen for suppressor mutations of the spr mutant phenotype revealed that deletion of tsp (prc), encoding a periplasmic carboxypeptidase involved in processing Spr and PBP3, restored intrinsic resistance to vancomycin and reversed the autolytic phenotype of the spr mutant. Our data suggest that Spr contributes to intrinsic antibiotic resistance in S. Typhimurium without directly affecting the outer membrane permeability barrier. Furthermore, our data suggests that compounds targeting specific cell wall endopeptidases might have the potential to expand the activity spectrum of traditional Gram-positive antibiotics. | 2018 | 30619108 |
| 6177 | 2 | 0.9973 | Genes involved in intrinsic antibiotic resistance of Acinetobacter baylyi. Bacterial genes defining intrinsic resistance to antibiotics encode proteins that can be targeted by antibiotic potentiators. To find such genes, a transposon insertion library of Acinetobacter baylyi was screened with subinhibitory concentrations of various antibiotics to find supersusceptible mutants. A DNA microarray printer was used to replica plate 10,000 individual library clones to select mutants unable to grow at 1/10 the MICs of 12 different antibiotics. Transposon insertions in 11 genes were found to cause an eightfold or higher hypersusceptibility to at least one antibiotic. Most of the mutants identified exhibited hypersusceptibility to beta-lactam antibiotics. These included mutants with disruptions of genes encoding proteins involved in efflux (acrB and oprM) as well as genes pertaining to peptidoglycan synthesis and modification (ampD, mpl, and pbpG). However, disruptions of genes encoding proteins with seemingly unrelated functions (gph, argH, hisF, and ACIAD0795) can also render cells hypersusceptible to beta-lactam antibiotics. A knockout of gshA, involved in glutathione biosynthesis, enhanced the susceptibility to metronidazole, while a knockout of recD, involved in recombination and repair, made the bacteria hypersusceptible to ciprofloxacin. Disruption of acrB in Escherichia coli rendered the cells hypersusceptible to several antibiotics. However, knockout mutants of other homologous genes in E. coli showed no significant changes in antibiotic MICs, indicating that the intrinsic resistance genes are species specific. | 2006 | 16940057 |
| 555 | 3 | 0.9973 | Mutations in dsbA and dsbB, but not dsbC, lead to an enhanced sensitivity of Escherichia coli to Hg2+ and Cd2+. The Dsb proteins are involved in disulfide bond formation, reduction and isomerisation in a number of Gram-negative bacteria. Mutations in dsbA or dsbB, but not dsbC, increase the proportion of proteins with free thiols in the periplasm compared to wild-type. We investigated the effects of mutations in these genes on the bacterial resistance to mercuric and cadmium salts. Mutations in genes involved primarily in disulfide formation (dsbA and dsbB) generally enhanced the sensitivity to Hg2+ and Cd2+ while a mutation of the dsbC gene (primarily an isomerase of disulfide bonds) had no effect. Mutations of the dsb genes had no effect on the expression of the mercury-resistance determinants of the transposon Tn501. | 1999 | 10234837 |
| 372 | 4 | 0.9972 | A chromosomal locus required for copper resistance, competitive fitness, and cytochrome c biogenesis in Pseudomonas fluorescens. A chromosomal locus required for copper resistance and competitive fitness was cloned from a strain of Pseudomonas fluorescens isolated from copper-contaminated agricultural soil. Sequence analysis of this locus revealed six open reading frames with homology to genes involved in cytochrome c biogenesis in other bacteria, helC, cycJ, cycK, tipB, cycL, and cycH, with the closest similarity being to the aeg-46.5(yej) region of the Escherichia coli chromosome. The proposed functions of these genes in other bacteria include the binding, transport, and coupling of heme to apocytochrome c in the periplasm of these Gram-negative bacteria. Putative heme-binding motifs were present in the predicted products of cycK and cycL, and TipB contained a putative disulfide oxidoreductase active site proposed to maintain the heme-binding site of the apocytochrome in a reduced state for ligation of heme. Tn3-gus mutagenesis showed that expression of the genes was constitutive but enhanced by copper, and confirmed that the genes function both in copper resistance and production of active cytochrome c. However, two mutants in cycH were copper-sensitive and oxidase-positive, suggesting that the functions of these genes, rather than cytochrome c oxidase itself, were required for resistance to copper. | 1996 | 8692990 |
| 373 | 5 | 0.9972 | The ybiT gene of Erwinia chrysanthemi codes for a putative ABC transporter and is involved in competitiveness against endophytic bacteria during infection. We investigated the role in bacterial infection of a putative ABC transporter, designated ybiT, of Erwinia chrysanthemi AC4150. The deduced sequence of this gene showed amino acid sequence similarity with other putative ABC transporters of gram-negative bacteria, such as Escherichia coli and Pseudomonas aeruginosa, as well as structural similarity with proteins of Streptomyces spp. involved in resistance to macrolide antibiotics. The gene contiguous to ybiT, designated as pab (putative antibiotic biosynthesis) showed sequence similarity with Pseudomonas and Streptomyces genes involved in the biosynthesis of antibiotics. A ybiT mutant (BT117) was constructed by marker exchange. It retained full virulence in potato tubers and chicory leaves, but it showed reduced ability to compete in planta against the wild-type strain or against selected saprophytic bacteria. These results indicate that the ybiT gene plays a role in the in planta fitness of the bacteria. | 2002 | 11916677 |
| 778 | 6 | 0.9971 | Identification and molecular characterization of an efflux pump involved in Pseudomonas putida S12 solvent tolerance. Bacteria able to grow in aqueous:organic two-phase systems have evolved resistance mechanisms to the toxic effects of solvents. One such mechanism is the active efflux of solvents from the cell, preserving the integrity of the cell interior. Pseudomonas putida S12 is resistant to a wide variety of normally detrimental solvents due to the action of such an efflux pump. The genes for this solvent efflux pump were cloned from P. putida S12 and their nucleotide sequence determined. The deduced amino acid sequences encoded by the three genes involved show a striking resemblance to proteins known to be involved in proton-dependent multidrug efflux systems. Transfer of the genes for the solvent efflux pump to solvent-sensitive P. putida strains results in the acquisition of solvent resistance. This opens up the possibilities of using the solvent efflux system to construct bacterial strains capable of performing biocatalytic transformations of insoluble substrates in two-phase aqueous:organic medium. | 1998 | 9417051 |
| 6356 | 7 | 0.9971 | Contribution of chloride channel permease to fluoride resistance in Streptococcus mutans. Genes encoding fluoride transporters have been identified in bacterial and archaeal species. The genome sequence of the cariogenic Streptococcus mutans bacteria suggests the presence of a putative fluoride transporter, which is referred to as a chloride channel permease. Two homologues of this gene (GenBank locus tags SMU_1290c and SMU_1289c) reside in tandem in the genome of S. mutans The aim of this study was to determine whether the chloride channel permeases contribute to fluoride resistance. We constructed SMU_1290c- and SMU_1289c-knockout S. mutans UA159 strains. We also constructed a double-knockout strain lacking both genes. SMU_1290c or SMU_1289c was transformed into a fluoride transporter- disrupted Escherichia coli strain. All bacterial strains were cultured under appropriate conditions with or without sodium fluoride, and fluoride resistance was evaluated. All three gene-knockout S. mutans strains showed lower resistance to sodium fluoride than did the wild-type strain. No significant changes in resistance to other sodium halides were recognized between the wild-type and double-knockout strains. Both SMU_1290c and SMU_1289c transformation rescued fluoride transporter-disrupted E. coli cell from fluoride toxicity. We conclude that the chloride channel permeases contribute to fluoride resistance in S. mutans. | 2016 | 27190286 |
| 6198 | 8 | 0.9971 | BC4707 is a major facilitator superfamily multidrug resistance transport protein from Bacillus cereus implicated in fluoroquinolone tolerance. Transcriptional profiling highlighted a subset of genes encoding putative multidrug transporters in the pathogen Bacillus cereus that were up-regulated during stress produced by bile salts. One of these multidrug transporters (BC4707) was selected for investigation. Functional characterization of the BC4707 protein in Escherichia coli revealed a role in the energized efflux of xenobiotics. Phenotypic analyses after inactivation of the gene bc4707 in Bacillus cereus ATCC14579 suggested a more specific, but modest role in the efflux of norfloxacin. In addition to this, transcriptional analyses showed that BC4707 is also expressed during growth of B. cereus under non-stressful conditions where it may have a role in the normal physiology of the bacteria. Altogether, the results indicate that bc4707, which is part of the core genome of the B. cereus group of bacteria, encodes a multidrug resistance efflux protein that is likely involved in maintaining intracellular homeostasis during growth of the bacteria. | 2012 | 22615800 |
| 6176 | 9 | 0.9971 | Involvement of GcvB small RNA in intrinsic resistance to multiple aminoglycoside antibiotics in Escherichia coli. Deleting the gene for small RNA GcvB in Escherichia coli was found to increase the sensitivity to several aminoglycoside antibiotics, such as neomycin, streptomycin, kanamycin, kasugamycin and spectinomycin, at low concentrations. GcvB, conserved in gram-negative enteric bacteria, is known to negatively control the expression of many genes for amino acid incorporation systems, especially the periplasmic ABC-transporter proteins. Deletions of several amino acid transporter genes in ΔgcvB cells decreased the antibiotic sensitivity to the wild-type level, suggesting that those genes are involved in uptake of aminoglycosides into the cell. Since GcvB is constitutively synthesized in growing cells, repressing synthesis of amino acid transporters, it contributes to the intrinsic resistance to several aminoglycoside antibiotics. | 2021 | 33169170 |
| 776 | 10 | 0.9970 | Exploring functional interplay amongst Escherichia coli efflux pumps. Bacterial efflux pumps exhibit functional interplay that can translate to additive or multiplicative effects on resistance to antimicrobial compounds. In diderm bacteria, two different efflux pump structural types - single-component inner membrane efflux pumps and cell envelope-spanning multicomponent systems - cooperatively export antimicrobials with cytoplasmic targets from the cell. Harnessing our recently developed efflux platform, which is built upon an extensively efflux-deficient strain of Escherichia coli, here we explore interplay amongst a panel of diverse E. coli efflux pumps. Specifically, we assessed the effect of simultaneously expressing two efflux pump-encoding genes on drug resistance, including single-component inner membrane efflux pumps (MdfA, MdtK and EmrE), tripartite complexes (AcrAB, AcrAD, MdtEF and AcrEF), and the acquired TetA(C) tetracycline resistance pump. Overall, the expression of two efflux pump-encoding genes from the same structural type did not enhance resistance levels regardless of the antimicrobial compound or efflux pump under investigation. In contrast, a combination of the tripartite efflux systems with single-component pumps sharing common substrates provided multiplicative increases to antimicrobial resistance levels. In some instances, resistance was increased beyond the product of resistance provided by the two pumps individually. In summary, the developed efflux platform enables the isolation of efflux pump function, facilitating the identification of interactions between efflux pumps. | 2022 | 36318669 |
| 6199 | 11 | 0.9970 | A bacterial gene homologous to ABC transporters protect Oenococcus oeni from ethanol and other stress factors in wine. The wine lactic acid bacteria Oenococcus oeni has to cope with harsh environmental conditions including an acidic pH, a high alcoholic content, non-optimal growth temperatures, and growth inhibitory compounds such as fatty acids, phenolic acids and tannins. We here describe characterisation and cloning of the O. oeni omrA gene encoding a protein belonging to the ATP-binding cassette superfamily of transporters. The OmrA protein displays the highest sequence similarity with the subfamily of ATP-dependent multidrug resistance (MDR) proteins, most notably the bacterial Lactococcus lactis LmrA homologue of the human MDR1 P-glycoprotein. The omrA gene proved to be a stress-responsive gene since its expression was increased at high temperature or under osmotic shock. The OmrA protein function was tested in Escherichia coli, and consistent with the omrA gene expression pattern, OmrA conferred protection to bacteria grown on a high salt medium. OmrA also triggered bacterial resistance to sodium laurate, wine and ethanol toxicity. The homologous LmrA protein featured the same stress-protective pattern than OmrA when expressed in E. coli, and the contribution to resistance of both OmrA and LmrA transporters was decreased by verapamil, a well-known inhibitor of the human MDR1 protein. Genes homologous to omrA were detected in other wine lactic acid bacteria, suggesting that this type of genes might constitute a well-conserved stress-protective molecular device. | 2004 | 15033264 |
| 643 | 12 | 0.9970 | Effect of overexpression of small non-coding DsrA RNA on multidrug efflux in Escherichia coli. OBJECTIVES: Several putative and proven drug efflux pumps are present in Escherichia coli. Because many such efflux pumps have overlapping substrate spectra, it is intriguing that bacteria, with their economically organized genomes, harbour such large sets of multidrug efflux genes. To understand how bacteria utilize these multiple efflux pumps, it is important to elucidate the process of pump expression regulation. The aim of this study was to determine a regulator of the multidrug efflux pump in this organism. METHODS: We screened a genomic library of E. coli for genes that decreased drug susceptibility in this organism. The library was developed from the chromosomal DNA of the MG1655 strain, and then the recombinant plasmids were transformed into an acrB-deleted strain. Transformants were screened for resistance to various antibiotics including oxacillin. RESULTS: We found that the multidrug susceptibilities of the acrB-deleted strain were decreased by the overexpression of small non-coding DsrA RNA as well as by the overexpression of known regulators of multidrug efflux pumps. Plasmids carrying the dsrA gene conferred resistance to oxacillin, cloxacillin, erythromycin, rhodamine 6G and novobiocin. DsrA decreased the accumulation of ethidium bromide in E. coli cells. Furthermore, expression of mdtE was significantly increased by dsrA overexpression, and the decreased multidrug susceptibilities modulated by DsrA were dependent on the MdtEF efflux pump. CONCLUSIONS: These results indicate that DsrA modulates multidrug efflux through activation of genes encoding the MdtEF pump in E. coli. | 2011 | 21088020 |
| 6189 | 13 | 0.9970 | Characterization of all RND-type multidrug efflux transporters in Vibrio parahaemolyticus. Resistance nodulation cell division (RND)-type efflux transporters play the main role in intrinsic resistance to various antimicrobial agents in many gram-negative bacteria. Here, we estimated 12 RND-type efflux transporter genes in Vibrio parahaemolyticus. Because VmeAB has already been characterized, we cloned the other 11 RND-type efflux transporter genes and characterized them in Escherichia coli KAM33 cells, a drug hypersusceptible strain. KAM33 expressing either VmeCD, VmeEF, or VmeYZ showed increased minimum inhibitory concentrations (MICs) for several antimicrobial agents. Additional four RND-type transporters were functional as efflux pumps only when co-expressed with VpoC, an outer membrane component in V. parahaemolyticus. Furthermore, VmeCD, VmeEF, and VmeYZ co-expressed with VpoC exhibited a broader substrate specificity and conferred higher resistance than that with TolC of E. coli. Deletion mutants of these transporter genes were constructed in V. parahaemolyticus. TM32 (ΔvmeAB and ΔvmeCD) had significantly decreased MICs for many antimicrobial agents and the number of viable cells after exposure to deoxycholate were markedly reduced. Strains in which 12 operons were all disrupted had very low MICs and much lower fluid accumulation in rabbit ileal loops. These results indicate that resistance nodulation cell division-type efflux transporters contribute not only to intrinsic resistance but also to exerting the virulence of V. parahaemolyticus. | 2013 | 23894076 |
| 769 | 14 | 0.9970 | Interspecies signalling: Pseudomonas putida efflux pump TtgGHI is activated by indole to increase antibiotic resistance. In Gram-negative bacteria, multidrug efflux pumps are responsible for the extrusion of chemicals that are deleterious for growth. Some of these efflux pumps are induced by endogenously produced effectors, while abiotic or biotic signals induce the expression of other efflux pumps. In Pseudomonas putida, the TtgABC efflux pump is the main antibiotic extrusion system that respond to exogenous antibiotics through the modulation of the expression of this operon mediated by TtgR. The plasmid-encoded TtgGHI efflux pump in P. putida plays a minor role in antibiotic resistance in the parental strain; however, its role is critical in isogenic backgrounds deficient in TtgABC. Expression of ttgGHI is repressed by the TtgV regulator that recognizes indole as an effector, although P. putida does not produce indole itself. Because indole is not produced by Pseudomonas, the indole-dependent antibiotic resistance seems to be part of an antibiotic resistance programme at the community level. Pseudomonas putida recognizes indole added to the medium or produced by Escherichia coli in mixed microbial communities. Transcriptomic analyses revealed that the indole-specific response involves activation of 43 genes and repression of 23 genes. Indole enhances not only the expression of the TtgGHI pump but also a set of genes involved in iron homeostasis, as well as genes for amino acid catabolism. In a ttgABC-deficient P. putida, background ampicillin and other bactericidal compounds lead to cell death. Co-culture of E. coli and P. putida ΔttgABC allowed growth of the P. putida mutant in the presence of ampicillin because of induction of the indole-dependent efflux pump. | 2014 | 24373097 |
| 6184 | 15 | 0.9970 | Active efflux as a mechanism of resistance to ciprofloxacin in Streptococcus pneumoniae. The accumulation of fluoroquinolones (FQs) was studied in a FQ-susceptible laboratory strain of Streptococcus pneumoniae (strain R6). Uptake of FQs was not saturable, was rapidly reversible, and appeared to occur by passive diffusion. In the presence of glucose, which energizes bacteria, the uptake of FQs decreased. Inhibitors of the proton motive force and ATP synthesis increased the uptake of FQs in previously energized bacteria. Similar results were observed with the various FQs tested and may be explained to be a consequence simply of the pH gradient that exists across the cytoplasmic membrane. From a clinical susceptible strain (strain SPn5907) we isolated in vitro on ciprofloxacin an FQ-resistant mutant (strain SPn5929) for which the MICs of hydrophilic molecules were greater than those of hydrophobic molecules, and the mutant was resistant to acriflavine, cetrimide, and ethidium bromide. Strain SPn5929 showed a significantly decreased uptake of ciprofloxacin, and its determinant of resistance to ciprofloxacin was transferred by transformation to susceptible laboratory strain R6 (strain R6tr5929). No mutations in the quinolone resistance-determining regions of the gyrA and parC genes were found. In the presence of arsenate or carbonyl cyanide m-chlorophenylhydrazone, the levels of uptake of ciprofloxacin by the two resistant strains, SPn5929 and R6tr5929, reached the levels of uptake of their susceptible parents. These results suggest an active efflux of ciprofloxacin in strain SPn5929. | 1997 | 9303396 |
| 6200 | 16 | 0.9970 | Heterologous expression of bacterial and human multidrug resistance proteins protect Escherichia coli against mercury and zinc contamination. In order to determine the role of multidrug resistance proteins in mercury and zinc resistance, human MDR1, Lactococcus lactis lmrA, and Oenococcus oeni omrA genes were expressed in an Escherichia coli tolC mutant which is hypersensitive to metals. The three transporters conferred an increased mercury and zinc resistance to E. coli as compared to the control bacteria. This improved resistance correlated with a decreased zinc and mercury bioaccumulation. Indeed, quantification of intracellular metal concentrations by atomic absorption spectrometry (AAS) showed a 2.1-, 3-, and 5.1-fold decrease in zinc in cells expressing hMDR1, omrA, and lmrA, respectively, and a 2.7-, 7.5-, and 7.7-fold decrease in mercury in cells expressing omrA, lmrA, and hMDR1, respectively, as compared to the control bacteria. This means that hMDR1, LmrA, and OmrA proteins which are specialised in xenobiotic scavenging, their main known function, are nevertheless able to confer some resistance against metals. Our results show that the tolC mutated strain is well adapted to the study of MDR transporter activity and could be used to screen substrates and competitive hMDR1 inhibitors. | 2006 | 16703280 |
| 165 | 17 | 0.9970 | An efflux transporter PbrA and a phosphatase PbrB cooperate in a lead-resistance mechanism in bacteria. The gene cluster pbrTRABCD from Cupriavidus metallidurans CH34 is thought to encode a unique, specific resistance mechanism for lead. However, the exact functions of these genes are unknown. In this study we examine the metal specificity and functions of pbrABCD by expressing these genes in different combinations and comparing their ability to restore Pb(2+), Zn(2+) and Cd(2+) resistance in a metal-sensitive C. metallidurans strain DN440. We show that lead resistance in C. metallidurans is achieved through the cooperation of the Zn/Cd/Pb-translocating ATPase PbrA and the undecaprenyl pyrophosphate phosphatase PbrB. While PbrA non-specifically exported Pb(2+), Zn(2+) and Cd(2+), a specific increase in lead resistance was observed when PbrA and PbrB were coexpressed. As a model of action for PbrA and PbrB we propose a mechanism where Pb(2+) is exported from the cytoplasm by PbrA and then sequestered as a phosphate salt with the inorganic phosphate produced by PbrB. Similar operons containing genes for heavy metal translocating ATPases and phosphatases were found in several different bacterial species, suggesting that lead detoxification through active efflux and sequestration is a common lead-resistance mechanism. | 2009 | 19737357 |
| 330 | 18 | 0.9970 | A DHA14 drug efflux gene from Xanthomonas albilineans confers high-level albicidin antibiotic resistance in Escherichia coli. AIMS: Identification of a gene for self-protection from the antibiotic-producing plant pathogen Xanthomonas albilineans, and functional testing by heterologous expression. METHODS AND RESULTS: Albicidin antibiotics and phytotoxins are potent inhibitors of prokaryote DNA replication. A resistance gene (albF) isolated by shotgun cloning from the X. albilineans albicidin-biosynthesis region encodes a protein with typical features of DHA14 drug efflux pumps. Low-level expression of albF in Escherichia coli increased the MIC of albicidin 3000-fold, without affecting tsx-mediated albicidin uptake into the periplasm or resistance to other tested antibiotics. Bioinformatic analysis indicates more similarity to proteins involved in self-protection in polyketide-antibiotic-producing actinomycetes than to multi-drug resistance pumps in other gram-negative bacteria. A complex promoter region may co-regulate albF with genes for hydrolases likely to be involved in albicidin activation or self-protection. CONCLUSIONS: AlbF is the first apparent single-component antibiotic-specific efflux pump from a gram-negative antibiotic producer. It shows extraordinary efficiency as measured by resistance level conferred upon heterologous expression. SIGNIFICANCE AND IMPACT OF THE STUDY: Development of the clinical potential of albicidins as potent bactericidial antibiotics against diverse bacteria has been limited because of low yields in culture. Expression of albF with recently described albicidin-biosynthesis genes may enable large-scale production. Because albicidins are X. albilineans pathogenicity factors, interference with AlbF function is also an opportunity for control of the associated plant disease. | 2006 | 16834602 |
| 8800 | 19 | 0.9970 | Expanded roles of lactate-sensing LldR in transcription regulation of the Escherichia coli K-12 genome: lactate utilisation and acid resistance. LldR is a lactate-responsive transcription factor (TF) that transcriptionally regulates the lldPRD operon consisting of lactate permease and lactate dehydrogenase. The lldPRD operon facilitates the utilisation of lactic acid in bacteria. However, the role of LldR in whole genomic transcriptional regulation, and the mechanism involved in adaptation to lactate remains unclear. We used genomic SELEX (gSELEX) to comprehensively analyse the genomic regulatory network of LldR to understand the overall regulatory mechanism of lactic acid adaptation of the model intestinal bacterium Escherichia coli. In addition to the involvement of the lldPRD operon in utilising lactate as a carbon source, genes related to glutamate-dependent acid resistance and altering the composition of membrane lipids were identified as novel targets of LldR. A series of in vitro and in vivo regulatory analyses led to the identification of LldR as an activator of these genes. Furthermore, the results of lactic acid tolerance tests and co-culture experiments with lactic acid bacteria suggested that LldR plays a significant role in adapting to the acid stress induced by lactic acid. Therefore, we propose that LldR is an l-/d-lactate sensing TF for utilising lactate as a carbon source and for resistance to lactate-induced acid stress in intestinal bacteria. | 2023 | 37219924 |