# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 8879 | 0 | 1.0000 | 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 |
| 8965 | 1 | 0.9998 | 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 |
| 8967 | 2 | 0.9997 | 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 |
| 6293 | 3 | 0.9997 | 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 |
| 8966 | 4 | 0.9997 | Gene expression profile of Campylobacter jejuni in response to macrolide antibiotics. Campylobacter jejuni is a foodborne pathogen that causes gastroenteritis in humans and has developed resistance to various antibiotics. The primary objective of this research was to examine the network of antibiotic resistance in C. jejuni. The study involved the wild and antibiotic-resistant strains placed in the presence and absence of antibiotics to review their gene expression profiles in response to ciprofloxacin via microarray. Differentially expressed genes (DEGs) analysis and Protein-Protein Interaction (PPI) Network studies were performed for these genes. The results showed that the resistance network of C. jejuni is modular, with different genes involved in bacterial motility, capsule synthesis, efflux, and amino acid and sugar synthesis. Antibiotic treatment resulted in the down-regulation of cluster genes related to translation, flagellum formation, and chemotaxis. In contrast, cluster genes involved in homeostasis, capsule formation, and cation efflux were up-regulated. The study also found that macrolide antibiotics inhibit the progression of C. jejuni infection by inactivating topoisomerase enzymes and increasing the activity of epimerase enzymes, trying to compensate for the effect of DNA twisting. Then, the bacterium limits the movement to conserve energy. Identifying the antibiotic resistance network in C. jejuni can aid in developing drugs to combat these bacteria. Genes involved in cell division, capsule formation, and substance transport may be potential targets for inhibitory drugs. Future research must be directed toward comprehending the underlying mechanisms contributing to the modularity of antibiotic resistance and developing strategies to disrupt and mitigate the growing threat of antibiotic resistance effectively. | 2024 | 38393387 |
| 6330 | 5 | 0.9997 | Transcriptomic study of ciprofloxacin resistance in Streptomyces coelicolor A3(2). Soil organisms exhibit resistance to a wide range of antibiotics as they either need to protect themselves from endogenous antibiotics or from those present in their soil environment. The soil could serve as a reservoir for resistance mechanisms that have already emerged or have the potential to emerge in clinically important bacteria. Streptomyces coelicolor, a non-pathogenic soil-dwelling organism, is thus used as a model for the study of intrinsic resistance. Preliminary screening of several compounds showed that S. coelicolor had high intrinsic resistance for the fluoroquinolone group of antibiotics. We subjected the bacteria to sub-inhibitory concentrations of ciprofloxacin and studied the transcriptomic response using microarrays. The data were supported with various biochemical and phenotypic assays. Ciprofloxacin treatment leads to differential expression of many genes with enhanced mRNA expression of its target, DNA gyrase gene. High induction of DNA repair pathways was also observed and many transporters were upregulated. Ciprofloxacin was found to induce ROS formation in a dose dependent manner. Reduction of ROS via anti-oxidants increased the effective MIC of the drug in the bacteria. The regulation of antibiotic resistance in S. coelicolor was studied systematically and contribution of different mechanisms in the development of resistance was assessed. Our data suggest that multiple mechanisms work in coordination to facilitate the cell to combat the stress due to ciprofloxacin. | 2013 | 24100886 |
| 6336 | 6 | 0.9997 | Comparative Analysis of Transcriptomic Response of Escherichia coli K-12 MG1655 to Nine Representative Classes of Antibiotics. The use of antibiotics leads to strong stresses to bacteria, leading to profound impact on cellular physiology. Elucidating how bacteria respond to antibiotic stresses not only helps us to decipher bacteria's strategies to resistant antibiotics but also assists in proposing targets for antibiotic development. In this work, a comprehensive comparative transcriptomic analysis on how Escherichia coli responds to nine representative classes of antibiotics (tetracycline, mitomycin C, imipenem, ceftazidime, kanamycin, ciprofloxacin, polymyxin E, erythromycin, and chloramphenicol) was performed, aimed at determining and comparing the responses of this model organism to antibiotics at the transcriptional level. On average, 39.71% of genes were differentially regulated by antibiotics at concentrations that inhibit 50% growth. Kanamycin leads to the strongest transcriptomic response (76.4% of genes regulated), whereas polymyxin E led to minimal transcriptomic response (4.7% of genes regulated). Further GO, KEGG, and EcoCyc enrichment analysis found significant transcriptomic changes in carbon metabolism, amino acid metabolism, nutrient assimilation, transport, stress response, nucleotide metabolism, protein biosynthesis, cell wall biosynthesis, energy conservation, mobility, and cell-environmental communications. Analysis of coregulated genes led to the finding of significant reduction of sulfur metabolism by all antibiotics, and analysis of transcription factor-coding genes suggested clustered regulatory patterns implying coregulation. In-depth analysis of regulated pathways revealed shared and unique strategies of E. coli resisting antibiotics, leading to the proposal of four different strategies (the pessimistic, the ignorant, the defensive, and the invasive). In conclusion, this work provides a comprehensive analysis of E. coli's transcriptomic response to antibiotics, which paves the road for further physiological investigation. IMPORTANCE Antibiotics are among the most important inventions in the history of humankind. They are the ultimate reason why bacterial infections are no longer the number one threat to people's lives. However, the wide application of antibiotics in the last half a century has led to aggravating antibiotic resistance, weakening the efficacy of antibiotics. To better comprehend the ways bacteria deal with antibiotics that may eventually turn into resistance mechanisms, and to identify good targets for potential antibiotics, knowledge on how bacteria regulate their physiology in response to different classes of antibiotics is needed. This work aimed to fill this knowledge gap by identifying changes of bacterial functions at the transcription level and suggesting strategies of bacteria to resist antibiotics. | 2023 | 36853057 |
| 8922 | 7 | 0.9997 | Transitioning from Soil to Host: Comparative Transcriptome Analysis Reveals the Burkholderia pseudomallei Response to Different Niches. Burkholderia pseudomallei, a soil and water saprophyte, is responsible for the tropical human disease melioidosis. A hundred years since its discovery, there is still much to learn about B. pseudomallei proteins that are essential for the bacterium's survival in and interaction with the infected host, as well as their roles within the bacterium's natural soil habitat. To address this gap, bacteria grown under conditions mimicking the soil environment were subjected to transcriptome sequencing (RNA-seq) analysis. A dual RNA-seq approach was used on total RNA from spleens isolated from a B. pseudomallei mouse infection model at 5 days postinfection. Under these conditions, a total of 1,434 bacterial genes were induced, with 959 induced in the soil environment and 475 induced in bacteria residing within the host. Genes encoding metabolism and transporter proteins were induced when the bacteria were present in soil, while virulence factors, metabolism, and bacterial defense mechanisms were upregulated during active infection of mice. On the other hand, capsular polysaccharide and quorum-sensing pathways were inhibited during infection. In addition to virulence factors, reactive oxygen species, heat shock proteins, siderophores, and secondary metabolites were also induced to assist bacterial adaptation and survival in the host. Overall, this study provides crucial insights into the transcriptome-level adaptations which facilitate infection by soil-dwelling B. pseudomallei. Targeting novel therapeutics toward B. pseudomallei proteins required for adaptation provides an alternative treatment strategy given its intrinsic antimicrobial resistance and the absence of a vaccine. IMPORTANCE Burkholderia pseudomallei, a soil-dwelling bacterium, is the causative agent of melioidosis, a fatal infectious disease of humans and animals. The bacterium has a large genome consisting of two chromosomes carrying genes that encode proteins with important roles for survival in diverse environments as well as in the infected host. While a general mechanism of pathogenesis has been proposed, it is not clear which proteins have major roles when the bacteria are in the soil and whether the same proteins are key to successful infection and spread. To address this question, we grew the bacteria in soil medium and then in infected mice. At 5 days postinfection, bacteria were recovered from infected mouse organs and their gene expression was compared against that of bacteria grown in soil medium. The analysis revealed a list of genes expressed under soil growth conditions and a different set of genes encoding proteins which may be important for survival, replication, and dissemination in an infected host. These proteins are a potential resource for understanding the full adaptation mechanism of this pathogen. In the absence of a vaccine for melioidosis and with treatment being reliant on combinatorial antibiotic therapy, these proteins may be ideal targets for designing antimicrobials to treat melioidosis. | 2023 | 36856434 |
| 6292 | 8 | 0.9997 | Genome-Wide Screening and Characterization of Genes Involved in Response to High Dose of Ciprofloxacin in Escherichia coli. The global emergence of antibiotic resistance, especially in Gram-negative bacteria, is an urgent threat to public health. Inevitably, considering its extensive use and misuse, resistance toward ciprofloxacin has increased in almost all clinically relevant bacteria. This study aimed to investigate the transcriptome changes at a high concentration of ciprofloxacin in Escherichia coli. In brief, 1,418 differentially expressed genes (DEGs) were identified, from which 773 genes were upregulated by ciprofloxacin, whereas 651 genes were downregulated. Enriched biological pathways reflected the upregulation of biological processes such as DNA damage and repair system, toxin/antitoxin systems, formaldehyde detoxification system. With kyoto encyclopedia of genes and genomes pathway analysis, higher expressed DEGs were associated with "LPS biosynthesis," "streptomycin biosynthesis," and "polyketide sugar unit biosynthesis." Lower expressed DEGs were associated with "biosynthesis of amino acids" and "flagellar assembly" pathways. After treatment of ciprofloxacin, lipopolysaccharide (LPS) release was increased by two times, and the gene expression level of LPS synthesis was elevated (p < 0.05) in both reference and clinical strains. Our results demonstrated that transient exposure to high-dose ciprofloxacin is a double-edged sword. Cautions should be taken when administering high-dose antibiotic treatment for infectious diseases. | 2022 | 35512736 |
| 8968 | 9 | 0.9996 | 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 |
| 8983 | 10 | 0.9996 | Chlorine disinfectants promote microbial resistance in Pseudomonas sp. The substantial use of disinfectants has increased antibiotic resistance, thereby mediating serious ecological safety issues worldwide. Accumulating studies have reported the role of chlorine disinfectants in promoting disinfectant resistance. The present study sought to investigate the role of chlorine disinfectants in developing multiple resistance in Pseudomonas sp. isolated from the river through antioxidant enzyme measurement, global transcriptional analyses, Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The results demonstrated that 100 mg/L sodium hypochlorite could increase disinfectant resistance and antibiotic resistance. The SOS response (a conserved response to DNA damage) triggered by oxidative stress makes bacteria resistant to chlorine. An increase in antibiotic resistance could be attributed to a decreased membrane permeability, increased expression of MuxABC-OpmB efflux pump, beta-lactamase, and antioxidant enzymes. Additionally, KEGG enrichment analysis suggested that the differentially expressed genes were highly enriched in the metabolic pathways. In summary, the study results revealed the impact of chlorine disinfectants in promoting microbial disinfectant resistance and antibiotic resistance. This study will provide insight into disinfectant resistance mechanisms. | 2021 | 34010624 |
| 8964 | 11 | 0.9996 | Analysis of the Oxidative Stress Regulon Identifies soxS as a Genetic Target for Resistance Reversal in Multidrug-Resistant Klebsiella pneumoniae. In bacteria, the defense system deployed to counter oxidative stress is orchestrated by three transcriptional factors, SoxS, SoxR, and OxyR. Although the regulon that these factors control is known in many bacteria, similar data are not available for Klebsiella pneumoniae. To address this data gap, oxidative stress was artificially induced in K. pneumoniae MGH78578 using paraquat and the corresponding oxidative stress regulon recorded using transcriptome sequencing (RNA-seq). The soxS gene was significantly induced during oxidative stress, and a knockout mutant was constructed to explore its functionality. The wild type and mutant were grown in the presence of paraquat and subjected to RNA-seq to elucidate the soxS regulon in K. pneumoniae MGH78578. Genes that are commonly regulated both in the oxidative stress and soxS regulons were identified and denoted as the oxidative SoxS regulon; these included a group of genes specifically regulated by SoxS. Efflux pump-encoding genes and global regulators were identified as part of this regulon. Consequently, the isogenic soxS mutant was found to exhibit a reduction in the minimum bactericidal concentration against tetracycline compared to that of the wild type. Impaired efflux activity, allowing tetracycline to be accumulated in the cytoplasm to bactericidal levels, was further evaluated using a tetraphenylphosphonium (TPP(+)) accumulation assay. The soxS mutant was also susceptible to tetracycline in vivo in a zebrafish embryo model. We conclude that the soxS gene could be considered a genetic target against which an inhibitor could be developed and used in combinatorial therapy to combat infections associated with multidrug-resistant K. pneumoniae. IMPORTANCE Antimicrobial resistance is a global health challenge. Few new antibiotics have been developed for use over the years, and preserving the efficacy of existing compounds is an important step to protect public health. This paper describes a study that examines the effects of exogenously induced oxidative stress on K. pneumoniae and uncovers a target that could be useful to harness as a strategy to mitigate resistance. | 2021 | 34098732 |
| 8880 | 12 | 0.9996 | 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 |
| 8951 | 13 | 0.9996 | Response mechanisms of resistance in L-form bacteria to different target antibiotics: Implications from oxidative stress to metabolism. Due to the specific action on bacterial cell wall, β-lactam antibiotics have gained widespread usage as they exhibit a high degree of specificity in targeting bacteria, but causing minimal toxicity to host cells. Under antibiotic pressure, bacteria may opt to shed their cell walls and transform into L-form state as a means to evade the antibiotic effects. In this study, we explored and identified diverse optimal conditions for both Gram-negative bacteria (E. coli DH5α (CTX)) and Gram-positive bacteria (B. subtilis ATCC6633), which were induced to L-form bacteria using lysozyme (0.5 ppm) and meropenem (64 ppm). Notably, when bacteria transformed into L-form state, both bacterial strains showed varying degrees of increased resistance to antibiotics polymyxin E, meropenem, rifampicin, and tetracycline. E. coli DH5α (CTX) exhibited the most significant enhancement in resistance to tetracycline, with a 128-fold increase, while B. subtilis ATCC6633 showed a 32-fold increase in resistance to tetracycline and polymyxin E. Furthermore, L-form bacteria maintained their normal metabolic activity, combined with enhanced oxidative stress, served as an adaptive strategy promoting the sustained survival of L-form bacteria. This study provided a theoretical basis for comprehending antibiotic resistance mechanisms, developing innovative treatment strategies, and confronting global antibiotic resistance challenges. | 2024 | 38735077 |
| 6329 | 14 | 0.9996 | Autoinducer-2 influences tetracycline resistance in Streptococcus suis by regulating the tet(M) gene via transposon Tn916. The concern over increasing resistance to tetracyclines (TCs), such as tetracycline and chlortetracycline, necessitates exploration of new approaches to combating infection in antimicrobial therapy. Given that bacteria use the chemical language of autoinducer 2 (AI-2) signaling molecules in order to communicate and regulate group behaviors, we asked whether the AI-2 signaling influence the tetracyclines antibiotics susceptibility in S. suis. Our present work demonstrated that MIC increased when exogenous AI-2 was added, when compared to the wild type strain. When grown in the presence of sub-MIC of antibiotics, it has been shown that exogenous AI-2 increases growth rate and biofilm formation. These results suggest that the TCs resistance in S. suis could involve a signaling mechanism. Base on the above observations, transcriptomic analyses showed significant differences in the expression of tet(M) of tetracyclines resistance genes, as well as differences in Tn916 transposon related genes transcription, as judged by RT-PCR. Our results provide strong evidence that AI-2 signaling molecules is may involve in TCs antibiotic resistance in S. suis by regulating tet(M) gene via Tn916 transposon. This study may suggest that targeting AI-2 signaling in bacteria could represent an alternative approach in antimicrobial therapy. | 2020 | 31837515 |
| 152 | 15 | 0.9996 | 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 |
| 683 | 16 | 0.9996 | 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 |
| 8957 | 17 | 0.9996 | Transcriptome Profiling Reveals Interplay of Multifaceted Stress Response in Escherichia coli on Exposure to Glutathione and Ciprofloxacin. We have previously reported that supplementation of exogenous glutathione (GSH) promotes ciprofloxacin resistance in Escherichia coli by neutralizing antibiotic-induced oxidative stress and by enhancing the efflux of antibiotic. In the present study, we used a whole-genome microarray as a tool to analyze the system-level transcriptomic changes of E. coli on exposure to GSH and/or ciprofloxacin. The microarray data revealed that GSH supplementation affects redox function, transport, acid shock, and virulence genes of E. coli. The data further highlighted the interplay of multiple underlying stress response pathways (including those associated with the genes mentioned above and DNA damage repair genes) at the core of GSH, offsetting the effect of ciprofloxacin in E. coli. The results of a large-scale validation of the transcriptomic data using reverse transcription-quantitative PCR (RT-qPCR) analysis for 40 different genes were mostly in agreement with the microarray results. The altered growth profiles of 12 different E. coli strains carrying deletions in the specific genes mentioned above with GSH and/or ciprofloxacin supplementation implicate these genes in the GSH-mediated phenotype not only at the molecular level but also at the functional level. We further associated GSH supplementation with increased acid shock survival of E. coli on the basis of our transcriptomic data. Taking the data together, it can be concluded that GSH supplementation influences the expression of genes of multiple stress response pathways apart from its effect(s) at the physiological level to counter the action of ciprofloxacin in E. coli. IMPORTANCE The emergence and spread of multidrug-resistant bacterial strains have serious medical and clinical consequences. In addition, the rate of discovery of new therapeutic antibiotics has been inadequate in last few decades. Fluoroquinolone antibiotics such as ciprofloxacin represent a precious therapeutic resource in the fight against bacterial pathogens. However, these antibiotics have been gradually losing their appeal due to the emergence and buildup of resistance to them. In this report, we shed light on the genome-level expression changes in bacteria with respect to glutathione (GSH) exposure which act as a trigger for fluoroquinolone antibiotic resistance. The knowledge about different bacterial stress response pathways under conditions of exposure to the conditions described above and potential points of cross talk between them could help us in understanding and formulating the conditions under which buildup and spread of antibiotic resistance could be minimized. Our findings are also relevant because GSH-induced genome-level expression changes have not been reported previously for E. coli. | 2018 | 29468195 |
| 8971 | 18 | 0.9996 | Bacteriophage induces modifications in outer membrane protein expression and antibiotic susceptibility in Acinetobacter baumannii. Bacteriophages, the most abundant biological agents targeting bacteria, offer a promising alternative to antibiotics for combating multi-drug resistant pathogens like Acinetobacter baumannii. However, the rapid development of bacteriophage resistance poses a significant challenge. This study highlights the contribution of outer membrane proteins (OMPs) in the emergence of bacteriophage resistance in A. baumannii. The bacteriophage-sensitive and resistant isolates were studied for their native OMP profiles. Bacteriophage-tolerant A. baumannii were generated by infecting bacteria with bacteriophages and sub-culturing the survivors, and their expression of OMP and virulence was further characterized. These tolerant strains had significantly downregulated omp genes and under-expressed OMPs. Phenotypic changes like reduced adsorption to phages, deviant growth rates, biofilm-forming capacities, higher survival in limiting conditions, higher motility, and higher alkaline protease production were observed in the phage-tolerant strains equipped with better survival and virulent properties. The tolerant strains were re-sensitized to antibiotics they previously resisted. The significantly under-expressed OMPs in phage-tolerant strains were identified as OmpA and other OMPs similar to OmpA. This study could identify certain OMPs significantly under-expressed on bacteriophage exposure. The tolerant bacteria had altered phenotypic properties in addition to the development of phage resistance and the re-sensitisation to antibiotics, which paved the way for the future of phage therapeutics. | 2025 | 39800016 |
| 6294 | 19 | 0.9996 | Comparison of Gene Expression Profiles of Uropathogenic Escherichia Coli CFT073 after Prolonged Exposure to Subinhibitory Concentrations of Different Biocides. Biocides are chemical compounds widely used for sterilization and disinfection. The aim of this study was to examine whether exposure to subinhibitory biocide concentrations influenced transcriptional expression of genes that could improve a pathogen's drug resistance or fitness. We used DNA microarrays to investigate the transcriptome of the uropathogenic Escherichia coli strain CFT073 in response to prolonged exposure to subinhibitory concentrations of four biocides: benzalkonium chloride, chlorhexidine, hydrogen peroxide and triclosan. Transcription of a gene involved in polymyxin resistance, arnT, was increased after treatment with benzalkonium chloride. However, pretreatment of the bacteria with this biocide did not result in cross-resistance to polymyxin in vitro. Genes encoding products related to transport formed the functional group that was most affected by biocides, as 110 out of 884 genes in this category displayed altered transcription. Transcripts of genes involved in cysteine uptake, sulfate assimilation, dipeptide transport, as well as cryptic phage genes were also more abundant in response to several biocides. Additionally, we identified groups of genes with transcription changes unique to single biocides that might include potential targets for the biocides. The biocides did not increase the resistance potential of the pathogen to other antimicrobials. | 2019 | 31569631 |