# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 638 | 0 | 1.0000 | Genetic Determinants of Salmonella enterica Serovar Typhimurium Proliferation in the Cytosol of Epithelial Cells. Intestinal epithelial cells provide an important colonization niche for Salmonella enterica serovar Typhimurium during gastrointestinal infections. In infected epithelial cells, a subpopulation of S Typhimurium bacteria damage their internalization vacuole, leading to escape from the Salmonella-containing vacuole (SCV) and extensive proliferation in the cytosol. Little is known about the bacterial determinants of nascent SCV lysis and subsequent survival and replication of Salmonella in the cytosol. To pinpoint S Typhimurium virulence factors responsible for these steps in the intracellular infectious cycle, we screened a S Typhimurium multigene deletion library in Caco-2 C2Bbe1 and HeLa epithelial cells for mutants that had an altered proportion of cytosolic bacteria compared to the wild type. We used a gentamicin protection assay in combination with a chloroquine resistance assay to quantify total and cytosolic bacteria, respectively, for each strain. Mutants of three S Typhimurium genes, STM1461 (ydgT), STM2829 (recA), and STM3952 (corA), had reduced cytosolic proliferation compared to wild-type bacteria, and one gene, STM2120 (asmA), displayed increased cytosolic replication. None of the mutants were affected for lysis of the nascent SCV or vacuolar replication in epithelial cells, indicating that these genes are specifically required for survival and proliferation of S Typhimurium in the epithelial cell cytosol. These are the first genes identified to contribute to this step of the S Typhimurium infectious cycle. | 2016 | 27698022 |
| 637 | 1 | 0.9994 | Identification of Bacillus subtilis sigma-dependent genes that provide intrinsic resistance to antimicrobial compounds produced by Bacilli. Bacillus subtilis produces many antibiotics of varying structures and specificity. Here we identify a prominent role for sigma(W), an extracytoplasmic function (ECF) sigma factor, in providing intrinsic resistance to antimicrobial compounds produced by other Bacilli. By using a panel of B. subtilis mutants disrupted for each of the 30 known sigma(W)-dependent operons we identified resistance genes for at least three different antimicrobial compounds. The ydbST and fosB genes contribute to resistance to antimicrobial compound(s) produced by B. amyloliquefaciens FZB42, the yqeZyqfAB operon provides resistance to the SPbeta prophage-encoded bacteriocin sublancin, and the yknWXYZ operon and yfhL provide resistance to the antimicrobial peptide SdpC. YfhL encodes a paralogue of SdpI, a membrane protein that provides immunity to SdpC. In competition experiments, we identify sigma(W) as a key factor in allowing B. subtilis to resist antibiotic killing and encroachment by competing strains. Together with the previous observation that sigma(W) provides inducible resistance against the Streptomyces antibiotic fosfomycin, these studies support the notion that sigma(W) controls an antibiosis regulon important in the microbial ecology of soil bacteria. | 2006 | 16629676 |
| 6171 | 2 | 0.9993 | Host response to infection with a temperature-sensitive mutant of Salmonella typhimurium in a susceptible and a resistant strain of mice. The inoculation of a temperature-sensitive mutant of Salmonella typhimurium induced a long-lasting infection in susceptible (C57BL/6) and resistant (A/J) mice. During week 1 of infection, the number of bacteria in the spleens was similar in both mouse strains. Then, the decrease of bacteria was more rapid in the resistant strain. Splenomegaly and granulomatous hepatitis were more severe in the susceptible strain. The immune response induced by this infection was studied. In both mouse strains delayed-type hypersensitivity to Salmonella antigens was present, and resistance to reinfection with a virulent strain of S. typhimurium or with Listeria monocytogenes appeared with the same kinetics. Thus, it does not seem that the gene(s) controlling natural resistance to S. typhimurium act(s) on acquired immunity. | 1985 | 3897053 |
| 8229 | 3 | 0.9993 | Molecular genetics, biochemistry and biological role of Yersinia lipopolysaccharide. Lipopolysaccharide (LPS) is the major component of the outer leaflet of the outer membrane of Gram-negative bacteria. The LPS molecule is composed of two biosynthetic entities: the lipid A--core and the O-polysaccharide (O-antigen). Most biological effects of LPS are due to the lipid A part, however, there is an increasing body of evidence also with Yersinia indicating that O-antigen plays an important role in effective colonization of host tissues, resistance to complement-mediated killing and in the resistance to cationic antimicrobial peptides that are key elements of the innate immune system. The biosynthesis of O-antigen requires numerous enzymatic activities and includes the biosynthesis of individual NDP-activated precursor sugars in the cytoplasm, linkage and sugar-specific transferases, O-unit flippase, O-antigen polymerase and O-chain length determinant. Based on this enzymatic mode of O-antigen biosynthesis LPS isolated from bacteria is a heterologous population of molecules; some do not carry any O-antigen while others that do have variation in the O-antigen chain lengths. The genes required for the O-antigen biosynthesis are located in O-antigen gene clusters that in genus Yersinia is located between the hemH and gsk genes. Temperature regulates the O-antigen expression in Y. enterocolitica and Y. pseudotuberculosis; bacteria grown at room temperature (RT, 22-25 degrees C) produce in abundance O-antigen while only trace amounts are present in bacteria grown at 37 degrees C. Even though the amount of O-antigen is known to fluctuate under different growth conditions in many bacteria very little detailed information is available on the control of the O-antigen biosynthetic machinery. | 2003 | 12756756 |
| 6208 | 4 | 0.9993 | Identification of bistable populations of Porphyromonas gingivalis that differ in epithelial cell invasion. Bistable populations of bacteria give rise to two or more subtypes that exhibit different phenotypes. We have explored whether the periodontal pathogen Porphyromonas gingivalis exhibits bistable invasive phenotypes. Using a modified cell invasion assay, we show for the first time that there are two distinct subtypes within a population of P. gingivalis strains NCTC 11834 and W50 that display differences in their ability to invade oral epithelial cells. The highly invasive subtype invades cells at 10-30-fold higher levels than the poorly invasive subtype and remains highly invasive for approximately 12-16 generations. Analysis of the gingipain activity of these subtypes revealed that the highly invasive type had reduced cell-associated arginine-specific protease activity. The role of Arg-gingipain activity in invasion was verified by enhancement of invasion by rgpAB mutations and by inclusion of an Arg-gingipain inhibitor in invasion assays using wild-type bacteria. In addition, a population of ΔrgpAB bacteria did not contain a hyperinvasive subtype. Screening of the protease activity of wild-type populations of both strains identified high and low protease subtypes which also showed a corresponding reduction or enhancement, respectively, of invasive capabilities. Microarray analysis of these bistable populations revealed a putative signature set of genes that includes oxidative stress resistance and iron transport genes, and which might be critical to invasion of or survival within epithelial cells. | 2010 | 20576685 |
| 635 | 5 | 0.9993 | Transcriptome of Dickeya dadantii infecting Acyrthosiphon pisum reveals a strong defense against antimicrobial peptides. The plant pathogenic bacterium Dickeya dadantii has recently been shown to be able to kill the aphid Acyrthosiphon pisum. While the factors required to cause plant disease are now well characterized, those required for insect pathogeny remain mostly unknown. To identify these factors, we analyzed the transcriptome of the bacteria isolated from infected aphids. More than 150 genes were upregulated and 300 downregulated more than 5-fold at 3 days post infection. No homologue to known toxin genes could be identified in the upregulated genes. The upregulated genes reflect the response of the bacteria to the conditions encountered inside aphids. While only a few genes involved in the response to oxidative stress were induced, a strong defense against antimicrobial peptides (AMP) was induced. Expression of a great number of efflux proteins and transporters was increased. Besides the genes involved in LPS modification by addition of 4-aminoarabinose (the arnBCADTEF operon) and phosphoethanolamine (pmrC, eptB) usually induced in Gram negative bacteria in response to AMPs, dltBAC and pbpG genes, which confer Gram positive bacteria resistance to AMPs by adding alanine to teichoic acids, were also induced. Both types of modification confer D. dadantii resistance to the AMP polymyxin. A. pisum harbors symbiotic bacteria and it is thought that it has a very limited immune system to maintain these populations and do not synthesize AMPs. The arnB mutant was less pathogenic to A. pisum, which suggests that, in contrast to what has been supposed, aphids do synthesize AMP. | 2013 | 23342088 |
| 8872 | 6 | 0.9993 | Dictyostelium discoideum as a model system for identification of Burkholderia pseudomallei virulence factors. Burkholderia pseudomallei is an emerging bacterial pathogen and category B biothreat. Human infections with B. pseudomallei (called melioidosis) present as a range of manifestations, including acute septicemia and pneumonia. Although melioidosis can be fatal, little is known about the molecular basis of B. pseudomallei pathogenicity, in part because of the lack of simple, genetically tractable eukaryotic models to facilitate en masse identification of virulence determinants or explore host-pathogen interactions. Two assays, one high-throughput and one quantitative, were developed to monitor levels of resistance of B. pseudomallei and the closely related nearly avirulent species Burkholderia thailandensis to predation by the phagocytic amoeba Dictyostelium discoideum. The quantitative assay showed that levels of resistance to, and survival within, amoeba by these bacteria and their known virulence mutants correlate well with their published levels of virulence in animals. Using the high-throughput assay, we screened a 1,500-member B. thailandensis transposon mutant library and identified 13 genes involved in resistance to predation by D. discoideum. Orthologs of these genes were disrupted in B. pseudomallei, and nearly all mutants had similarly decreased resistance to predation by D. discoideum. For some mutants, decreased resistance also correlated with reduced survival in and cytotoxicity toward macrophages, as well as attenuated virulence in mice. These observations suggest that some factors required by B. pseudomallei for resistance to environmental phagocytes also aid in resistance to phagocytic immune cells and contribute to disease in animals. Thus, D. discoideum provides a novel, high-throughput model system for facilitating inquiry into B. pseudomallei virulence. | 2011 | 21402765 |
| 6170 | 7 | 0.9993 | Resistance and susceptibility of mice to bacterial infection. IV. Functional specificity in natural resistance to facultative intracellular bacteria. The effect of opsonic antibody on resistance of susceptibility of three strains of mice, C57Bl/10, BALB/c, and CBA to the intracellular bacteria Listeria monocytogenes, Salmonella typhimurium, and Brucella abortus was tested. Bacteria were opsonized by serum treatment before their injection into mice, or the mice were preimmunized by injection with alcohol killed bacteria which induces antibody without macrophage activation. Antibody did not increase the rate of clearance of Listeria from the bloodstream, nor did it affect the subsequent growth of that organism in the spleen and liver. Blood clearance of S. typhimurium and of B. abortus was increased by preopsonization with specific antibody, indicating that opsonins were a limiting factor in resistance to these two bacteria. However, neither opsonization before infection nor immunization with alcohol killed vaccines had any effect on the strain distribution of resistance/susceptibility, which differs for each of the three intracellular pathogens. Thus, even in the presence of adequate opsonization the three strains of mice showed different patterns of resistance/susceptibility to Listeria, S. typhimurium, and B. abortus. This implies that each has a unique cellular mechanism of early nonspecific resistance. | 1983 | 6413682 |
| 8897 | 8 | 0.9993 | Clinically relevant mutant DNA gyrase alters supercoiling, changes the transcriptome, and confers multidrug resistance. Bacterial DNA is maintained in a supercoiled state controlled by the action of topoisomerases. Alterations in supercoiling affect fundamental cellular processes, including transcription. Here, we show that substitution at position 87 of GyrA of Salmonella influences sensitivity to antibiotics, including nonquinolone drugs, alters global supercoiling, and results in an altered transcriptome with increased expression of stress response pathways. Decreased susceptibility to multiple antibiotics seen with a GyrA Asp87Gly mutant was not a result of increased efflux activity or reduced reactive-oxygen production. These data show that a frequently observed and clinically relevant substitution within GyrA results in altered expression of numerous genes, including those important in bacterial survival of stress, suggesting that GyrA mutants may have a selective advantage under specific conditions. Our findings help contextualize the high rate of quinolone resistance in pathogenic strains of bacteria and may partly explain why such mutant strains are evolutionarily successful. IMPORTANCE: Fluoroquinolones are a powerful group of antibiotics that target bacterial enzymes involved in helping bacteria maintain the conformation of their chromosome. Mutations in the target enzymes allow bacteria to become resistant to these antibiotics, and fluoroquinolone resistance is common. We show here that these mutations also provide protection against a broad range of other antimicrobials by triggering a defensive stress response in the cell. This work suggests that fluoroquinolone resistance mutations may be beneficial under a range of conditions. | 2013 | 23882012 |
| 688 | 9 | 0.9993 | The cop operon is required for copper homeostasis and contributes to virulence in Streptococcus pneumoniae. High levels of copper are toxic and therefore bacteria must limit free intracellular levels to prevent cellular damage. In this study, we show that a number of pneumococcal genes are differentially regulated by copper, including an operon encoding a CopY regulator, a protein of unknown function (CupA) and a P1-type ATPase, CopA, which is conserved in all sequenced Streptococcus pneumoniae strains. Transcriptional analysis demonstrated that the cop operon is induced by copper in vitro, repressed by the addition of zinc and is autoregulated by the copper-responsive CopY repressor protein. We also demonstrate that the CopA ATPase is a major pneumococcal copper resistance mechanism and provide the first evidence that the CupA protein plays a role in copper resistance. Our results also show that copper homeostasis is important for pneumococcal virulence as the expression of the cop operon is induced in the lungs and nasopharynx of intranasally infected mice, and a copA(-) mutant strain, which had decreased growth in high levels of copper in vitro, showed reduced virulence in a mouse model of pneumococcal pneumonia. Furthermore, using the copA(-) mutant we observed for the first time in any bacteria that copper homeostasis also appears to be required for survival in the nasopharynx. | 2011 | 21736642 |
| 6342 | 10 | 0.9993 | Determinants of Extreme β-Lactam Tolerance in the Burkholderia pseudomallei Complex. Slow-growing bacteria are insensitive to killing by antibiotics, a trait known as antibiotic tolerance. In this study, we characterized the genetic basis of an unusually robust β-lactam (meropenem) tolerance seen in Burkholderia species. We identified tolerance genes under three different slow-growth conditions by extensive transposon mutant sequencing (Tn-seq), followed by single mutant validation. There were three principal findings. First, mutations in a small number of genes reduced tolerance under multiple conditions. Most of the functions appeared to be specific to peptidoglycan synthesis and the response to its disruption by meropenem action rather than being associated with more general physiological processes. The top tolerance genes are involved in immunity toward a type VI toxin targeting peptidoglycan (BTH_I0069), peptidoglycan recycling (ldcA), periplasmic regulation by proteolysis (prc), and an envelope stress response (rpoE and degS). Second, most of the tolerance functions did not contribute to growth in the presence of meropenem (intrinsic resistance), indicating that the two traits are largely distinct. Third, orthologues of many of the top Burkholderia thailandensis tolerance genes were also important in Burkholderia pseudomallei Overall, these studies show that the determinants of meropenem tolerance differ considerably depending on cultivation conditions, but that there are a few shared functions with strong mutant phenotypes that are important in multiple Burkholderia species. | 2018 | 29439964 |
| 6206 | 11 | 0.9993 | Transcriptomic data of Salmonella enterica subsp. enterica serovar Typhimurium str. 14028S treated with novobiocin. In enteric bacteria, DNA supercoiling is highly responsive to environmental conditions. Host specific features of environment serve as cues for the expression of genes required for colonization of host niches via changing supercoiling [1]. It has been shown that substitution at position 87 of GyrA of Salmonella enterica str. SL1344 influences global supercoiling and results in an altered transcriptome with increased expression of stress response pathways [2]. Aminocoumarin antibiotics, such as novobiocin, can be used to relax supercoiling and alter the expression of supercoiling-sensitive genes. Meanwhile, Salmonella enterica demonstrates a significant resistance to this antibiotic and relatively small variability of supercoiling in response to the growth phase, osmotic pressure, and novobiocin treatment. Here we present for the first time transcriptome data of Salmonella enterica subsp. Enterica serovar Typhimurium str. 14028S grown in the presence of novobiocin. These data will help identify genes involved in novobiocin resistance and adaptation processes associated with torsion perturbations in S. enterica. Cleaned FASTQ files for the RNA-seq libraries are deposited in the NCBI Sequence Read Archive (SRA, Identifier: SRP239815) and have been assigned BioProject accession PRJNA599397. | 2020 | 32140513 |
| 6314 | 12 | 0.9993 | Identification of genes involved in the resistance of mycobacteria to killing by macrophages. The survival of M. leprae and M. tuberculosis in the human host is dependent upon their ability to produce gene products that counteract the bactericidal activities of macrophages. To identify such mycobacterial genes and gene products, recombinant DNA libraries of mycobacterial DNA in E. coli were passed through macrophages to enrich for clones carrying genes that endow the normally susceptible E. coli bacteria with an enhanced ability to survive within macrophages. Following three cycles of enrichment, 15 independent clones were isolated. Three recombinants were characterized in detail, and each confers significantly enhanced survival on E. coli cells carrying them. Two of the cloned genetic elements also confer enhanced survival onto M. smegmatis cells. Further characterization of these genes and gene products should provide insights into the survival of mycobacteria within macrophages and may identify new approaches of targets for combatting these important pathogens. | 1994 | 8080180 |
| 689 | 13 | 0.9992 | Regulatory and DNA repair genes contribute to the desiccation resistance of Sinorhizobium meliloti Rm1021. Sinorhizobium meliloti can form a nitrogen-fixing symbiotic relationship with alfalfa after bacteria in the soil infect emerging root hairs of the growing plant. To be successful at this, the bacteria must be able to survive in the soil between periods of active plant growth, including when conditions are dry. The ability of S. meliloti to withstand desiccation has been known for years, but genes that contribute to this phenotype have not been identified. Transposon mutagenesis was used in combination with novel screening techniques to identify four desiccation-sensitive mutants of S. meliloti Rm1021. DNA sequencing of the transposon insertion sites identified three genes with regulatory functions (relA, rpoE2, and hpr) and a DNA repair gene (uvrC). Various phenotypes of the mutants were determined, including their behavior on several indicator media and in symbiosis. All of the mutants formed an effective symbiosis with alfalfa. To test the hypothesis that UvrC-related excision repair was important in desiccation resistance, uvrA, uvrB, and uvrC deletion mutants were also constructed. These strains were sensitive to DNA damage induced by UV light and 4-NQO and were also desiccation sensitive. These data indicate that uvr gene-mediated DNA repair and the regulation of stress-induced pathways are important for desiccation resistance. | 2009 | 19028909 |
| 446 | 14 | 0.9992 | Identification of Lactobacillus reuteri genes specifically induced in the mouse gastrointestinal tract. Lactobacilli are common inhabitants of the gastrointestinal tracts of mammals and have received considerable attention due to their putative health-promoting properties. Little is known about the traits that enhance the ability of these bacteria to inhabit the gastrointestinal tract. In this paper we describe the development and application of a strategy based on in vivo expression technology (IVET) that enables detection of Lactobacillus reuteri genes specifically induced in the murine gut. A plasmid-based system was constructed containing 'ermGT (which confers lincomycin resistance) as the primary reporter gene for selection of promoters active in the gastrointestinal tract of mice treated with lincomycin. A second reporter gene, 'bglM (beta-glucanase), allowed differentiation between constitutive and in vivo inducible promoters. The system was successfully tested in vitro and in vivo by using a constitutive promoter. Application of the IVET system with chromosomal DNA of L. reuteri 100-23 and reconstituted lactobacillus-free mice revealed three genes induced specifically during colonization. Two of the sequences showed homology to genes encoding xylose isomerase (xylA) and peptide methionine sulfoxide reductase (msrB), which are involved in nutrient acquisition and stress responses, respectively. The third locus showed homology to the gene encoding a protein whose function is not known. Our IVET system has the potential to identify genes of lactobacilli that have not previously been functionally characterized but which may be essential for growth of these bacteria in the gastrointestinal ecosystem. | 2003 | 12676681 |
| 6219 | 15 | 0.9992 | Isolation and characterization of bacteriophage-resistant mutants of Vibrio cholerae O139. Vibrio cholerae O139 strains produce a capsule which is associated with complement resistance and is used as a receptor by bacteriophage JA1. Spontaneous JA1-resistant mutants were found to have several phenotypes, with loss of capsule and/or O-antigen from the cell surface. Determination of the residual complement resistance and infant mouse colonization potential of each mutant suggested that production of O-antigen is of much greater significance than the presence of capsular material for both of these properties. Two different in vitro assays of complement resistance were compared and the results of one shown to closely reflect the comparative recoveries of bacteria from the colonization experiments. Preliminary complementation studies implicated two rfb region genes, wzz and wbfP, as being essential for the biosynthesis of capsule but not O-antigen. | 2001 | 11312617 |
| 6217 | 16 | 0.9992 | Identification of the sigmaB regulon of Bacillus cereus and conservation of sigmaB-regulated genes in low-GC-content gram-positive bacteria. The alternative sigma factor sigma(B) has an important role in the acquisition of stress resistance in many gram-positive bacteria, including the food-borne pathogen Bacillus cereus. Here, we describe the identification of the set of sigma(B)-regulated genes in B. cereus by DNA microarray analysis of the transcriptome upon a mild heat shock. Twenty-four genes could be identified as being sigma(B) dependent as witnessed by (i) significantly lower expression levels of these genes in mutants with a deletion of sigB and rsbY (which encode the alternative sigma factor sigma(B) and a crucial positive regulator of sigma(B) activity, respectively) than in the parental strain B. cereus ATCC 14579 and (ii) increased expression of these genes upon a heat shock. Newly identified sigma(B)-dependent genes in B. cereus include a histidine kinase and two genes that have predicted functions in spore germination. This study shows that the sigma(B) regulon of B. cereus is considerably smaller than that of other gram-positive bacteria. This appears to be in line with phylogenetic analyses where sigma(B) of the B. cereus group was placed close to the ancestral form of sigma(B) in gram-positive bacteria. The data described in this study and previous studies in which the complete sigma(B) regulon of the gram-positive bacteria Bacillus subtilis, Listeria monocytogenes, and Staphylococcus aureus were determined enabled a comparison of the sets of sigma(B)-regulated genes in the different gram-positive bacteria. This showed that only three genes (rsbV, rsbW, and sigB) are conserved in their sigma(B) dependency in all four bacteria, suggesting that the sigma(B) regulon of the different gram-positive bacteria has evolved to perform niche-specific functions. | 2007 | 17416654 |
| 8388 | 17 | 0.9992 | Essential genes from Arctic bacteria used to construct stable, temperature-sensitive bacterial vaccines. All bacteria share a set of evolutionarily conserved essential genes that encode products that are required for viability. The great diversity of environments that bacteria inhabit, including environments at extreme temperatures, place adaptive pressure on essential genes. We sought to use this evolutionary diversity of essential genes to engineer bacterial pathogens to be stably temperature-sensitive, and thus useful as live vaccines. We isolated essential genes from bacteria found in the Arctic and substituted them for their counterparts into pathogens of mammals. We found that substitution of nine different essential genes from psychrophilic (cold-loving) bacteria into mammalian pathogenic bacteria resulted in strains that died below their normal-temperature growth limits. Substitution of three different psychrophilic gene orthologs of ligA, which encode NAD-dependent DNA ligase, resulted in bacterial strains that died at 33, 35, and 37 degrees C. One ligA gene was shown to render Francisella tularensis, Salmonella enterica, and Mycobacterium smegmatis temperature-sensitive, demonstrating that this gene functions in both Gram-negative and Gram-positive lineage bacteria. Three temperature-sensitive F. tularensis strains were shown to induce protective immunity after vaccination at a cool body site. About half of the genes that could be tested were unable to mutate to temperature-resistant forms at detectable levels. These results show that psychrophilic essential genes can be used to create a unique class of bacterial temperature-sensitive vaccines for important human pathogens, such as S. enterica and Mycobacterium tuberculosis. | 2010 | 20624965 |
| 6207 | 18 | 0.9992 | The tellurite resistance gene cluster of pathogenic bacteria and its effect on oxidative stress response. Tellurite resistance gene clusters have been identified in numerous pathogenic bacteria, including clinical isolates of Escherichia coli. The rareness of tellurium in host organisms and the noncontaminated environment raises a question about the true functionality of tellurite resistance gene clusters in pathogenesis and their possible contribution to bacterial fitness. The study aims to point out the beneficial effects of the tellurite resistance gene cluster of pathogenic bacteria to survive in ROS-rich environments. Here, we analysed the bacterial response to oxidative stress conditions with and without tellurite resistance gene clusters, which are composed of terWY1XY2Y3 and terZABCDEF genes. By measuring the levels of protein carbonylation, lipid peroxidation, and expression changes of oxidative stress genes upon oxidative stress, we propose a tellurite resistance gene cluster contribution to the elimination of oxidative damage, potentially increasing fitness and resistance to reactive oxygen species during macrophage attack. We have shown a different beneficial effect of various truncated versions of the tellurite resistance gene cluster on cell survival. The terBCDEF genes increased the survival of E. coli strain MC4100 by 13.21%, terW and terZABCDEF by 10.09%, and terWY1XY2Y3 and terZABCDEF by 25.57%, respectively. The ability to survive tellurite treatment is the most significant at 44.8% in wild clinical strain KL53 compared to laboratory strain E. coli MC4100 due to a complete wild-type plasmid presence. | 2024 | 38261148 |
| 8946 | 19 | 0.9992 | Role of the CpxAR two-component signal transduction system in control of fosfomycin resistance and carbon substrate uptake. Although fosfomycin is an old antibiotic, it has resurfaced with particular interest. The antibiotic is still effective against many pathogens that are resistant to other commonly used antibiotics. We have found that fosfomycin resistance of enterohemorrhagic Escherichia coli (EHEC) O157:H7 is controlled by the bacterial two-component signal transduction system CpxAR. A cpxA mutant lacking its phosphatase activity results in constitutive activation of its cognate response regulator, CpxR, and fosfomycin resistance. We have shown that fosfomycin resistance requires CpxR because deletion of the cpxR gene in the cpxA mutant restores fosfomycin sensitivity. We have also shown that CpxR directly represses the expression of two genes, glpT and uhpT, which encode transporters that cotransport fosfomycin with their native substrates glycerol-3-phosphate and glucose-6-phosphate, and repression of these genes leads to a decrease in fosfomycin transport into the cpxA mutant. However, the cpxA mutant had an impaired growth phenotype when cultured with glycerol-3-phosphate or glucose-6-phosphate as a sole carbon substrate and was outcompeted by the parent strain, even in nutrient-rich medium. This suggests a trade-off between fosfomycin resistance and the biological fitness associated with carbon substrate uptake. We propose a role for the CpxAR system in the reversible control of fosfomycin resistance. This may be a beneficial strategy for bacteria to relieve the fitness burden that results from fosfomycin resistance in the absence of fosfomycin. | 2014 | 24163343 |