# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 151 | 0 | 1.0000 | Enhanced NADH Metabolism Involves Colistin-Induced Killing of Bacillus subtilis and Paenibacillus polymyxa. The commonly believed mechanism of colistin against Gram-negative bacteria is to cause cell membrane lysis, whereas the mechanism of colistin against Gram-positive bacteria is extremely fragmented. In this study, we found that colistin treatment on Bacillus subtilis WB800, Paenibacillus polymyxa C12 and Paenibacillus polymyxa ATCC842 enhances not only the activities of α-ketoglutaric dehydrogenase and malate dehydrogenase in tricarboxylic acid (TCA) cycle, but also the relative expression levels of their encoding genes. Additionally, the oxaloacetate concentration also increases. Interestingly, the analysis of the relative expression of genes specific for respiratory chain showed that colistin treatment stimulates the respiratory chain in Gram-positive bacteria. Accordingly, the NAD⁺/NADH ratio increases and the oxidative level is then boosted up. As a result, the intensive oxidative damages are induced in Gram-positive bacteria and cells are killed. Notably, both rotenone and oligomycin, respectively, inhibiting NADH dehydrogenase and phosphorylation on respiratory chain can downgrade oxidative stress formation, thus alleviating the colistin-induced killing of Gram-positive cells. Besides, thiourea-based scavenging for reactive oxygen species also rescues the colistin-subjected cells. These data collectively demonstrate that colistin stimulates both TCA cycle and respiratory chain in Gram-positive bacteria, leading to the enhancement of NADH metabolism and resulting in the generation of oxidative damages in Gram-positive cells. Our studies provide a better understanding of antibacterial mechanism of colistin against Gram-positive bacteria, which is important for knowledge on bacterial resistance to colistin happening via the inhibition of respiratory chain and manipulation of its production. | 2019 | 30678237 |
| 8976 | 1 | 0.9994 | Biosynthesis of H(2)S and Siderophores Targeting Gram-Negative Bacterial Resistance to Reactive Oxygen Species. Reactive oxygen species (ROS) are a promising alternative bactericide. However, it is questioned that bacteria can potentially develop resistance to ROS, similar to their resistance against antibiotics and silver. Herein, it is reported that Gram-negative bacteria, including Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae, develop resistance to ROS after six repeated exposures. Notably, ROS minimum inhibitory concentration of Pseudomonas aeruginosa significantly increases to 256-fold after ten passages. The resistance mechanism predominantly originates from the intensified biosynthesis of the highly reductive hydrogen sulfide (H(2)S) and pyoverdine (PVD) siderophores, effectively neutralizing ROS. Simultaneously, PVD transports Fe(3+) from the extracellular space into the bacteria, releasing H(2)S bound to Fe(3+) and enhancing ROS scavenging. Additionally, the enhanced outer membrane (OM) biogenesis establishes a robust OM barrier, impeding ROS penetration. The acquired resistance to ROS can be significantly reduced by incorporating additional Fe(3+) into the culture medium or disrupting the H(2)S biosynthetic gene. These observations suggest that careful consideration is required when utilizing ROS against Gram-negative bacteria. It is anticipated that understanding this resistance mechanism can inform the development of future antimicrobial agents, particularly for Gram-negative bacteria. | 2025 | 40948366 |
| 152 | 2 | 0.9994 | Metabolic mechanism of colistin resistance and its reverting in Vibrio alginolyticus. Colistin is a last-line antibiotic against Gram-negative multidrug-resistant bacteria, but the increased resistance poses a huge challenge to this drug. However, the mechanisms underlying such resistance are largely unexplored. The present study first identified the mutations of two genes encoding AceF subunit of pyruvate dehydrogenase (PDH) and TetR family transcriptional regulator in colistin-resistant Vibrio alginolyticus (VA-R(CT) ) through genome sequencing. Then, gas chromatography-mass spectroscopy-based metabolomics was adopted to investigate metabolic responses since PDH plays a role in central carbon metabolism. Colistin resistance was associated with the reduction of the central carbon metabolism and energy metabolism, featuring the alteration of the pyruvate cycle, a recently characterized energy-producing cycle. Metabolites in the pyruvate cycle reprogramed colistin-resistant metabolome to colistin-sensitive metabolome, resulting in increased gene expression, enzyme activity or protein abundance of the cycle and sodium-translocating nicotinamide adenine dinucleotide-ubiquinone oxidoreductase. This reprogramming promoted the production of the proton motive force that enhances the binding between colistin and lipid A in lipopolysaccharide. Moreover, this metabolic approach was effective against VA-R(CT) in vitro and in vivo as well as other clinical isolates. These findings reveal a previously unknown mechanism of colistin resistance and develop a metabolome-reprogramming approach to promote colistin efficiency to combat with colistin-resistant bacteria. | 2020 | 32291842 |
| 8880 | 3 | 0.9994 | Nisin and acid resistance in Salmonella is enhanced by N-dodecanoyl-homoserine lactone. Salmonella is a foodborne pathogen that can develop resistance to different stresses, which is essential for successful infection of the host. Some genes directly related to acid resistance are also involved in cationic peptide resistance in Gram-negative bacteria and could be under the control of quorum sensing (QS) mediated by autoinducer 1, known as acyl-homoserine lactone. Here, we investigated the influence of autoinducer 1, N-dodecanoyl-homoserine lactone (C12-HSL) on the resistance of Salmonella enterica subspecies enterica serovar Enteritidis to nisin and acid stress. Salmonella cells growing in anaerobic tryptic soy agar (TSB) at a pH of 7.0 for 7 h were submitted to acid stress at a pH of 4.5 in the presence and absence of nisin and were either supplemented or not with C12-HSL. Viable cell counts, gene expression, membrane charge alterations, fatty acid composition, and intracellular content leakage were observed. The autoinducer C12-HSL increased nisin resistance and survival at a pH of 4.5 in Salmonella. Also, C12-HSL increased the expression of the genes, phoP, phoQ, pmrA, and pmrB, which are involved with antimicrobial and acid resistance. The positive charge on the cell surface and concentration of cyclopropane fatty acid of the cellular membrane were increased in the presence of C12-HSL under acidic conditions, whereas membrane fluidity decreased. The loss of K(+) and NADPH, promoted by nisin, was reduced in the presence of C12-HSL at a pH of 4.5. Taken together, these findings suggest that quorum sensing plays an important role in enhanced nisin and acid resistance in Salmonella. | 2020 | 32534181 |
| 157 | 4 | 0.9994 | Analysis of proteins responsive to acetic acid in Acetobacter: molecular mechanisms conferring acetic acid resistance in acetic acid bacteria. Acetic acid bacteria are used for industrial vinegar production because of their remarkable ability to oxidize ethanol and high resistance to acetic acid. Although several molecular machineries responsible for acetic acid resistance in acetic acid bacteria have been reported, the entire mechanism that confers acetic acid resistance has not been completely understood. One of the promising methods to elucidate the entire mechanism is global analysis of proteins responsive to acetic acid by two-dimensional gel electrophoresis. Recently, two proteins whose production was greatly enhanced by acetic acid in Acetobacter aceti were identified to be aconitase and a putative ABC-transporter, respectively; furthermore, overexpression or disruption of the genes encoding these proteins affected acetic acid resistance in A. aceti, indicating that these proteins are involved in acetic acid resistance. Overexpression of each gene increased acetic acid resistance in Acetobacter, which resulted in an improvement in the productivity of acetic acid fermentation. Taken together, the results of the proteomic analysis and those of previous studies indicate that acetic acid resistance in acetic acid bacteria is conferred by several mechanisms. These findings also provide a clue to breed a strain having high resistance to acetic acid for vinegar fermentation. | 2008 | 17920150 |
| 8813 | 5 | 0.9994 | Enhancing Escherichia coli abiotic stress resistance through ornithine lipid formation. Escherichia coli is a common host for biotechnology and synthetic biology applications. During growth and fermentation, the microbes are often exposed to stress conditions, such as variations in pH or solvent concentrations. Bacterial membranes play a key role in response to abiotic stresses. Ornithine lipids (OLs) are a group of membrane lipids whose presence and synthesis have been related to stress resistance in bacteria. We wondered if this stress resistance could be transferred to bacteria not encoding the capacity to form OLs in their genome, such as E. coli. In this study, we engineered different E. coli strains to produce unmodified OLs and hydroxylated OLs by expressing the synthetic operon olsFC. Our results showed that OL formation improved pH resistance and increased biomass under phosphate limitation. Transcriptome analysis revealed that OL-forming strains differentially expressed stress- and membrane-related genes. OL-producing strains also showed better growth in the presence of the ionophore carbonyl cyanide 3-chlorophenylhydrazone (CCCP), suggesting reduced proton leakiness in OL-producing strains. Furthermore, our engineered strains showed improved heterologous violacein production at phosphate limitation and also at low pH. Overall, this study demonstrates the potential of engineering the E. coli membrane composition for constructing robust hosts with an increased abiotic stress resistance for biotechnology and synthetic biology applications. KEY POINTS: • Ornithine lipid production in E. coli increases biomass yield under phosphate limitation. • Engineered strains show an enhanced production phenotype under low pH stress. • Transcriptome analysis and CCCP experiments revealed reduced proton leakage. | 2024 | 38587638 |
| 8682 | 6 | 0.9994 | Role of manganese superoxide dismutase (Mn-SOD) against Cr(III)-induced toxicity in bacteria. The toxicity of Cr(VI) was widely investigated, but the defense mechanism against Cr(III) in bacteria are seldom reported. Here, we found that Cr(III) inhibited bacterial growth and induced reactive oxygen species (ROS). After exposure to Cr(III), loss of sodA not only led to the excessive generation of ROS, but also enhanced the level of lipid peroxidation and reduced the GSH level, indicating that the deficiency of Mn-SOD decreased the bacterial resistance ability against Cr(III). The adverse effects of oxidative stress caused by Cr(III) could be recovered by the rescue of Mn-SOD in the sodA-deficient strain. Besides the oxidative stress, Cr(III) could cause the bacterial morphology variation, which was distinct between the wild-type and the sodA-deficient strains due to the differential expressions of Z-ring division genes. Moreover, Mn-SOD might prevent Cr(III) from oxidation on the bacterial surface by combining with Cr(III). Taken together, our results indicated that the Mn-SOD played a vital role in regulating the stress resistance, expression of cell division-related genes, bacterial morphology, and chemistry valence state of Cr. Our findings firstly provided a more in-depth understanding of Cr(III) toxicity and bacterial defense mechanism against Cr(III). | 2021 | 32781281 |
| 720 | 7 | 0.9994 | Escherichia Coli Increases its ATP Concentration in Weakly Acidic Environments Principally through the Glycolytic Pathway. Acid resistance is an intrinsic characteristic of intestinal bacteria in order to survive passage through the stomach. Adenosine triphosphate (ATP), the ubiquitous chemical used to power metabolic reactions, activate signaling cascades, and form precursors of nucleic acids, was also found to be associated with the survival of Escherichia coli (E. coli) in acidic environments. The metabolic pathway responsible for elevating the level of ATP inside these bacteria during acid adaptation has been unclear. E. coli uses several mechanisms of ATP production, including oxidative phosphorylation, glycolysis and the oxidation of organic compounds. To uncover which is primarily used during adaptation to acidic conditions, we broadly analyzed the levels of gene transcription of multiple E. coli metabolic pathway components. Our findings confirmed that the primary producers of ATP in E. coli undergoing mild acidic stress are the glycolytic enzymes Glk, PykF and Pgk, which are also essential for survival under markedly acidic conditions. By contrast, the transcription of genes related to oxidative phosphorylation was downregulated, despite it being the major producer of ATP in neutral pH environments. | 2020 | 32854287 |
| 8965 | 8 | 0.9994 | Resistance characterization and transcriptomic analysis of imipenem-induced drug resistance in Escherichia coli. BACKGROUND: Bacteria can develop resistance to various antibiotics under selective pressure, leading to multifaceted changes in resistance mechanisms. Transcriptomic sequencing allows for the observation of transcriptional level alterations in cells under antibiotic stress. Understanding the bacterial response to such stress is essential for deciphering their strategy against drug-resistant antibiotics and identifying potential targets for antibiotic development. METHODS: This study using wild-type (WT) Escherichia coli (E. coli) discovered that continuous in vitro induction screening for imipenem-resistant strains resulted in bacteria with enhanced biofilm-forming ability and mutations in antibiotic target sites. Transcriptomic sequencing of the resistant bacteria revealed significant changes in carbon and amino acid metabolism, nutrient assimilation, substance transport, nucleotide metabolism, protein biosynthesis, and cell wall biosynthesis. The up-regulated drug efflux genes were disrupted using gene knockout technology. Drug sensitivity tests indicated that drug efflux has a minimal effect on imipenem resistance. RESULTS: This suggests a strategy for E. coli drug resistance involving the reduction of unnecessary substance synthesis and metabolism, coupled with an increase in activities that aid in resisting foreign threats. | 2024 | 39624129 |
| 8942 | 9 | 0.9994 | Indole-Induced Activities of β-Lactamase and Efflux Pump Confer Ampicillin Resistance in Pseudomonas putida KT2440. Indole, which is widespread in microbial communities, has received attention because of its effects on bacterial physiology. Pseudomonas putida and Pseudomonas aeruginosa can acquire ampicillin (Amp) resistance during growth on indole-Amp agar. Transcriptome, mutant, and inhibitor studies have suggested that Amp resistance induced by indole can be attributed to increased gene expression of ttgAB encoding two genes of RND-type multidrug efflux operons and an ampC encoding β-lactamase. Expression, enzyme activities, and mutational analyses indicated that AmpC β-lactamase is important for acquiring Amp resistance of P. putida in the presence of indole. Here, we show, for the first time, that volatile indole increased Amp-resistant cells. Consistent with results of the volatile indole assay, a low concentration of indole in liquid culture promoted growth initially, but led to mutagenesis after indole was depleted, which could not be observed at high indole concentrations. Interestingly, ttgAB and ampC gene expression levels correlate with the concentration of indole, which might explain the low number of Amp-mutated cells in high indole concentrations. The expression levels of genes involved in mutagenesis, namely rpoS, recA, and mutS, were also modulated by indole. Our data indicates that indole reduces Amp-induced heterogeneity by promoting expression of TtgABC or MexAB-OprM efflux pumps and the indole-induced β-lactamase in P. putida and P. aeruginosa. | 2017 | 28352264 |
| 8967 | 10 | 0.9994 | Distinct transcriptomic response of S. coelicolor to ciprofloxacin in a nutrient-rich environment. With the rising threat of anti-microbial resistance (AMR), there is an urgent need to enhance efficacy of existing antibiotics. Understanding the myriad mechanisms through which bacteria evade these drugs would be of immense value to designing novel strategies against them. Streptomyces coelicolor A3(2) M145 belongs to the actinomyctes species that are responsible for more than two-thirds of antibiotics. This group of bacteria therefore encodes for various mechanisms that can resist both endogenous and non-endogenous antibiotics. In an earlier study, we had studied the transcriptomic response of these bacteria to ciprofloxacin, when cultured in a minimal media. In this work, we investigate why the minimum inhibitory concentration of the drug increases by fourfold when the bacteria are grown in a nutrient-rich media. Through transcriptomic, biochemical, and microscopic studies, we show that S. coelicolor responds to ciprofloxacin in a concentration-dependent manner. While, sub-inhibitory concentration of the drug primarily causes oxidative stress, the inhibitory concentration of ciprofloxacin evokes a more severe genome-wide response in the cell, which ranges from the familiar upregulation of the SOS response and DNA repair pathways to the widespread alterations in the central metabolism pathway to accommodate the increased needs of nucleotides and other precursors. Further, the upregulation of peptidoglycan synthesis genes, along with microscopy images, suggest alterations in the cell morphology to increase fitness of the bacteria during the antibiotic stress. The data also points to the enhanced efflux activity in cells cultured in rich media that contributes significantly towards reducing intracellular drug concentration and thus promotes survival. | 2018 | 30327831 |
| 8879 | 11 | 0.9993 | Global metabolic regulation in Vibrio parahaemolyticus under polymyxin B stimulation. Vibrio parahaemolyticus is responsible for infection diseases of people who consume the contaminated seafood, but its metabolic regulation profile in response to colistin, the last treatment option for multidrug-resistant Gram-negative bacteria, remains unclear. In this study, the metabolic regulation profile of V. parahaemolyticus ATCC33846 under polymyxin B stimulation has been investigated. V. parahaemolyticus exposed to polymyxin B resulted in 4597 differentially transcribed genes, including 673 significantly up-regulated genes and 569 significantly down-regulated genes. In V. parahaemolyticus under polymyxin B stimulation, the cellular antioxidant systems to prevent bacteria from oxidant stress was activated, the synthesis of some nonessential macromolecules was reduced, and the assembly and modification of lipopolysaccharide and peptidoglycan to resist the attack from other antibiotics were promoted. These findings provide new insights into polymyxin B-related stress response in V. parahaemolyticus which should be useful for developing novel drugs for infection. | 2021 | 34688850 |
| 683 | 12 | 0.9993 | Integrative Multiomics Analysis of the Heat Stress Response of Enterococcus faecium. A continuous heat-adaptation test was conducted for one Enterococcus faecium (E. faecium) strain wild-type (WT) RS047 to obtain a high-temperature-resistant strain. After domestication, the strain was screened with a significantly higher ability of heat resistance. which is named RS047-wl. Then a multi-omics analysis of transcriptomics and metabolomics was used to analyze the mechanism of the heat resistance of the mutant. A total of 98 differentially expressed genes (DEGs) and 115 differential metabolites covering multiple metabolic processes were detected in the mutant, which indicated that the tolerance of heat resistance was regulated by multiple mechanisms. The changes in AgrB, AgrC, and AgrA gene expressions were involved in quorum-sensing (QS) system pathways, which regulate biofilm formation. Second, highly soluble osmotic substances such as putrescine, spermidine, glycine betaine (GB), and trehalose-6P were accumulated for the membrane transport system. Third, organic acids metabolism and purine metabolism were down-regulated. The findings can provide target genes for subsequent genetic modification of E. faecium, and provide indications for screening heat-resistant bacteria, so as to improve the heat-resistant ability of E. faecium for production. | 2023 | 36979372 |
| 6293 | 13 | 0.9993 | Gentamicin resistance to Escherichia coli related to fatty acid metabolism based on transcriptome analysis. Antibiotic overuse and misuse have promoted the emergence and spread of antibiotic-resistant bacteria. Increasing bacterial resistance to antibiotics is a major healthcare problem, necessitating elucidation of antibiotic resistance mechanisms. In this study, we explored the mechanism of gentamicin resistance by comparing the transcriptomes of antibiotic-sensitive and -resistant Escherichia coli. A total of 410 differentially expressed genes were identified, of which 233 (56.83%) were up-regulated and 177 (43.17%) were down-regulated in the resistant strain compared with the sensitive strain. Gene Ontology (GO) analysis classifies differential gene expression into three main categories: biological processes, cellular components, and molecular functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the up-regulated genes were enriched in eight metabolic pathways, including fatty acid metabolism, which suggests that fatty acid metabolism may be involved in the development of gentamicin resistance in E. coli. This was demonstrated by measuring the acetyl-CoA carboxylase activity, plays a fundamental role in fatty acid metabolism, was increased in gentamicin-resistant E. coli. Treatment of fatty acid synthesis inhibitor, triclosan, promoted gentamicin-mediated killing efficacy to antibiotic-resistant bacteria. We also found that exogenous addition of oleic acid, which involved in fatty acid metabolism, reduced E. coli sensitivity to gentamicin. Overall, our results provide insight into the molecular mechanism of gentamicin resistance development in E. coli. | 2023 | 37224563 |
| 8216 | 14 | 0.9993 | The Effect of glycocholic acid on the growth, membrane permeability, conjugation and antibiotic susceptibility of Enterobacteriaceae. INTRODUCTION: Glycocholic acid (GCA) is a steroid acid and one of the main glycine-conjugated bile components in mammalian bile, which is involved in the emulsification and absorption of fats and sterols. It is long-known that the amphipathic nature of bile acids enables them to interact with the lipid membrane of Gram-positive bacteria and act as potent antimicrobial compounds. Nevertheless, Gram-negative Enterobacteriaceae species inhabiting the intestinal tract of mammals are considered to be more bile-resistant compared to Gram-positive bacteria and are thought to tolerate high bile concentrations. RESULTS: Here, we show that 1-2% of GCA inhibit the growth of Enterobacteriaceae species, including E. coli, Salmonella enterica. Klebsiella spp., Citrobacter spp., and Raoultella spp. during their late logarithmic phase in liquid culture, but not in solid media. Despite their lipopolysaccharide membrane layer, we demonstrate that, in liquid, GCA increases permeability, changes the surface of the Enterobacteriaceae membrane, and compromises its integrity. These changes result in leakage of cytoplasmic proteins and enhancement of their susceptibility to antibiotics. Moreover, GCA significantly reduces bacterial motility, the frequency of bacterial conjugation and horizontal acquisition of antibiotic resistance genes. These phenotypes are associated with repression of flagellin (fliC) transcription and a sharp decrease in the occurrence of conjugative pili in the presence of glycocholic acid, respectively. DISCUSSION: Overall, these findings broaden the current understanding about bile resistance of Gram-negative bacteria and suggest that GCA can be used to inhibit bacterial growth, augment the activity of antimicrobial compounds and diminish acquisition and dissemination of antibiotic resistance genes by conjugation. | 2025 | 40256452 |
| 8301 | 15 | 0.9993 | Metabolic disruption impairs ribosomal protein levels, resulting in enhanced aminoglycoside tolerance. Aminoglycoside antibiotics target ribosomes and are effective against a wide range of bacteria. Here, we demonstrated that knockout strains related to energy metabolism in Escherichia coli showed increased tolerance to aminoglycosides during the mid-exponential growth phase. Contrary to expectations, these mutations did not reduce the proton motive force or aminoglycoside uptake, as there were no significant changes in metabolic indicators or intracellular gentamicin levels between wild-type and mutant strains. Our comprehensive proteomics analysis unveiled a noteworthy upregulation of proteins linked to the tricarboxylic acid (TCA) cycle in the mutant strains during the mid-exponential growth phase, suggesting that these strains compensate for the perturbation in their energy metabolism by increasing TCA cycle activity to maintain their membrane potential and ATP levels. Furthermore, our pathway enrichment analysis shed light on local network clusters displaying downregulation across all mutant strains, which were associated with both large and small ribosomal binding proteins, ribosome biogenesis, translation factor activity, and the biosynthesis of ribonucleoside monophosphates. These findings offer a plausible explanation for the observed tolerance of aminoglycosides in the mutant strains. Altogether, this research provides valuable insights into the mechanisms of aminoglycoside tolerance, paving the way for novel strategies to combat such cells. | 2024 | 39093940 |
| 8968 | 16 | 0.9993 | Antibiotic stress, genetic response and altered permeability of E. coli. BACKGROUND: Membrane permeability is the first step involved in resistance of bacteria to an antibiotic. The number and activity of efflux pumps and outer membrane proteins that constitute porins play major roles in the definition of intrinsic resistance in Gram-negative bacteria that is altered under antibiotic exposure. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe the genetic regulation of porins and efflux pumps of Escherichia coli during prolonged exposure to increasing concentrations of tetracycline and demonstrate, with the aid of quantitative real-time reverse transcriptase-polymerase chain reaction methodology and western blot detection, the sequence order of genetic expression of regulatory genes, their relationship to each other, and the ensuing increased activity of genes that code for transporter proteins of efflux pumps and down-regulation of porin expression. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that, in addition to the transcriptional regulation of genes coding for membrane proteins, the post-translational regulation of proteins involved in the permeability of Gram-negative bacteria also plays a major role in the physiological adaptation to antibiotic exposure. A model is presented that summarizes events during the physiological adaptation of E. coli to tetracycline exposure. | 2007 | 17426813 |
| 158 | 17 | 0.9993 | Homology- and cross-resistance of Lactobacillus plantarum to acid and osmotic stress and the influence of induction conditions on its proliferation by RNA-Seq. In this study, homology- and cross-resistance of Lactobacillus plantarum L1 and Lactobacillus plantarum L2 to acid and osmotic stress were investigated. Meanwhile, its proliferation mechanism was demonstrated by transcriptomic analysis using RNA sequencing. We found that the homologous-resistance and cross-resistance of L. plantarum L1 and L. plantarum L2 increased after acid and osmotic induction treatment by lactic acid and sodium lactate solution in advance, and the survival rate of live bacteria was improved. In addition, the count of viable bacteria of L. plantarum L2 significantly increased cultivated at a pH 5.0 with a 15% sodium lactate sublethal treatment, compared with the control group. Further study revealed that genes related to membrane transport, amino acid metabolism, nucleotide metabolism, and cell growth were significantly upregulated. These findings will contribute to promote high-density cell culture of starter cultures production in the fermented food industry. | 2021 | 33945164 |
| 8943 | 18 | 0.9993 | Effects of indole on drug resistance and virulence of Salmonella enterica serovar Typhimurium revealed by genome-wide analyses. BACKGROUND: Many Gram-positive and Gram-negative bacteria produce large quantities of indole as an intercellular signal in microbial communities. Indole demonstrated to affect gene expression in Escherichia coli as an intra-species signaling molecule. In contrast to E. coli, Salmonella does not produce indole because it does not harbor tnaA, which encodes the enzyme responsible for tryptophan metabolism. Our previous study demonstrated that E. coli-conditioned medium and indole induce expression of the AcrAB multidrug efflux pump in Salmonella enterica serovar Typhimurium for inter-species communication; however, the global effect of indole on genes in Salmonella remains unknown. RESULTS: To understand the complete picture of genes regulated by indole, we performed DNA microarray analysis of genes in the S. enterica serovar Typhimurium strain ATCC 14028s affected by indole. Predicted Salmonella phenotypes affected by indole based on the microarray data were also examined in this study. Indole induced expression of genes related to efflux-mediated multidrug resistance, including ramA and acrAB, and repressed those related to host cell invasion encoded in the Salmonella pathogenicity island 1, and flagella production. Reduction of invasive activity and motility of Salmonella by indole was also observed phenotypically. CONCLUSION: Our results suggest that indole is an important signaling molecule for inter-species communication to control drug resistance and virulence of S. enterica. | 2012 | 22632036 |
| 8308 | 19 | 0.9993 | PhoPQ Regulates Quinolone and Cephalosporin Resistance Formation in Salmonella Enteritidis at the Transcriptional Level. The two-component system (TCS) PhoPQ has been demonstrated to be crucial for the formation of resistance to quinolones and cephalosporins in Salmonella Enteritidis (S. Enteritidis). However, the mechanism underlying PhoPQ-mediated antibiotic resistance formation remains poorly understood. Here, it was shown that PhoP transcriptionally regulated an assortment of genes associated with envelope homeostasis, the osmotic stress response, and the redox balance to confer resistance to quinolones and cephalosporins in S. Enteritidis. Specifically, cells lacking the PhoP regulator, under nalidixic acid and ceftazidime stress, bore a severely compromised membrane on the aspects of integrity, fluidity, and permeability, with deficiency to withstand osmolarity stress, an increased accumulation of intracellular reactive oxygen species, and dysregulated redox homeostasis, which are unfavorable for bacterial survival. The phosphorylated PhoP elicited transcriptional alterations of resistance-associated genes, including the outer membrane porin ompF and the aconitate hydratase acnA, by directly binding to their promoters, leading to a limited influx of antibiotics and a well-maintained intracellular metabolism. Importantly, it was demonstrated that the cavity of the PhoQ sensor domain bound to and sensed quinolones/cephalosporins via the crucial surrounding residues, as their mutations abrogated the binding and PhoQ autophosphorylation. This recognition mode promoted signal transduction that activated PhoP, thereby modulating the transcription of downstream genes to accommodate cells to antibiotic stress. These findings have revealed how bacteria employ a specific TCS to sense antibiotics and combat them, suggesting PhoPQ as a potential drug target with which to surmount S. Enteritidis. IMPORTANCE The prevalence of quinolone and cephalosporin-resistant S. Enteritidis is of increasing clinical concern. Thus, it is imperative to identify novel therapeutic targets with which to treat S. Enteritidis-associated infections. The PhoPQ two-component system is conserved across a variety of Gram-negative pathogens, by which bacteria adapt to a range of environmental stimuli. Our earlier work has demonstrated the importance of PhoPQ in the resistance formation in S. Enteritidis to quinolones and cephalosporins. In the current work, we identified a global profile of genes that are regulated by PhoP under antibiotic stresses, with a focus on how PhoP regulated downstream genes, either positively or negatively. Additionally, we established that PhoQ sensed quinolones and cephalosporins in a manner of directly binding to them. These identified genes and pathways that are mediated by PhoPQ represent promising targets for the development of a drug potentiator with which to neutralize antibiotic resistance in S. Enteritidis. | 2023 | 37184399 |