# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 725 | 0 | 0.9943 | The Bacillus subtilis extracytoplasmic function σ factor σ(V) is induced by lysozyme and provides resistance to lysozyme. Bacteria encounter numerous environmental stresses which can delay or inhibit their growth. Many bacteria utilize alternative σ factors to regulate subsets of genes required to overcome different extracellular assaults. The largest group of these alternative σ factors are the extracytoplasmic function (ECF) σ factors. In this paper, we demonstrate that the expression of the ECF σ factor σ(V) in Bacillus subtilis is induced specifically by lysozyme but not other cell wall-damaging agents. A mutation in sigV results in increased sensitivity to lysozyme killing, suggesting that σ(V) is required for lysozyme resistance. Using reverse transcription (RT)-PCR, we show that the previously uncharacterized gene yrhL (here referred to as oatA for O-acetyltransferase) is in a four-gene operon which includes sigV and rsiV. In quantitative RT-PCR experiments, the expression of oatA is induced by lysozyme stress. Lysozyme induction of oatA is dependent upon σ(V). Overexpression of oatA in a sigV mutant restores lysozyme resistance to wild-type levels. This suggests that OatA is required for σ(V)-dependent resistance to lysozyme. We also tested the ability of lysozyme to induce the other ECF σ factors and found that only the expression of sigV is lysozyme inducible. However, we found that the other ECF σ factors contributed to lysozyme resistance. We found that sigX and sigM mutations alone had very little effect on lysozyme resistance but when combined with a sigV mutation resulted in significantly greater lysozyme sensitivity than the sigV mutation alone. This suggests that sigV, sigX, and sigM may act synergistically to control lysozyme resistance. In addition, we show that two ECF σ factor-regulated genes, dltA and pbpX, are required for lysozyme resistance. Thus, we have identified three independent mechanisms which B. subtilis utilizes to avoid killing by lysozyme. | 2011 | 21856855 |
| 543 | 1 | 0.9940 | OxyR2 Modulates OxyR1 Activity and Vibrio cholerae Oxidative Stress Response. Bacteria have developed capacities to deal with different stresses and adapt to different environmental niches. The human pathogen Vibrio cholerae, the causative agent of the severe diarrheal disease cholera, utilizes the transcriptional regulator OxyR to activate genes related to oxidative stress resistance, including peroxiredoxin PrxA, in response to hydrogen peroxide. In this study, we identified another OxyR homolog in V. cholerae, which we named OxyR2, and we renamed the previous OxyR OxyR1. We found that OxyR2 is required to activate its divergently transcribed gene ahpC, encoding an alkylhydroperoxide reductase, independently of H(2)O(2) A conserved cysteine residue in OxyR2 is critical for this function. Mutation of either oxyR2 or ahpC rendered V. cholerae more resistant to H(2)O(2) RNA sequencing analyses indicated that OxyR1-activated oxidative stress-resistant genes were highly expressed in oxyR2 mutants even in the absence of H(2)O(2) Further genetic analyses suggest that OxyR2-activated AhpC modulates OxyR1 activity by maintaining low intracellular concentrations of H(2)O(2) Furthermore, we showed that ΔoxyR2 and ΔahpC mutants were less fit when anaerobically grown bacteria were exposed to low levels of H(2)O(2) or incubated in seawater. These results suggest that OxyR2 and AhpC play important roles in the V. cholerae oxidative stress response. | 2017 | 28138024 |
| 547 | 2 | 0.9939 | Dual role of OhrR as a repressor and an activator in response to organic hydroperoxides in Streptomyces coelicolor. Organic hydroperoxide resistance in bacteria is achieved primarily through reducing oxidized membrane lipids. The soil-inhabiting aerobic bacterium Streptomyces coelicolor contains three paralogous genes for organic hydroperoxide resistance: ohrA, ohrB, and ohrC. The ohrA gene is transcribed divergently from ohrR, which encodes a putative regulator of MarR family. Both the ohrA and ohrR genes were induced highly by various organic hydroperoxides. The ohrA gene was induced through removal of repression by OhrR, whereas the ohrR gene was induced through activation by OhrR. Reduced OhrR bound to the ohrA-ohrR intergenic region, which contains a central (primary) and two adjacent (secondary) inverted-repeat motifs that overlap with promoter elements. Organic peroxide decreased the binding affinity of OhrR for the primary site, with a concomitant decrease in cooperative binding to the adjacent secondary sites. The single cysteine C28 in OhrR was involved in sensing oxidants, as determined by substitution mutagenesis. The C28S mutant of OhrR bound to the intergenic region without any change in binding affinity in response to organic peroxides. These results lead us to propose a model for the dual action of OhrR as a repressor and an activator in S. coelicolor. Under reduced conditions, OhrR binds cooperatively to the intergenic region, repressing transcription from both genes. Upon oxidation, the binding affinity of OhrR decreases, with a concomitant loss of cooperative binding, which allows RNA polymerase to bind to both the ohrA and ohrR promoters. The loosely bound oxidized OhrR can further activate transcription from the ohrR promoter. | 2007 | 17586628 |
| 546 | 3 | 0.9939 | Resistance to organic hydroperoxides requires ohr and ohrR genes in Sinorhizobium meliloti. BACKGROUND: Sinorhizobium meliloti is a symbiotic nitrogen-fixing bacterium that elicits nodules on roots of host plants Medicago sativa. During nodule formation bacteria have to withstand oxygen radicals produced by the plant. Resistance to H2O2 and superoxides has been extensively studied in S. meliloti. In contrast resistance to organic peroxides has not been investigated while S. meliloti genome encodes putative organic peroxidases. Organic peroxides are produced by plants and are highly toxic. The resistance to these oxygen radicals has been studied in various bacteria but never in plant nodulating bacteria. RESULTS: In this study we report the characterisation of organic hydroperoxide resistance gene ohr and its regulator ohrR in S. meliloti. The inactivation of ohr affects resistance to cumene and ter-butyl hydroperoxides but not to hydrogen peroxide or menadione in vitro. The expression of ohr and ohrR genes is specifically induced by organic peroxides. OhrR binds to the intergenic region between the divergent genes ohr and ohrR. Two binding sites were characterised. Binding to the operator is prevented by OhrR oxidation that promotes OhrR dimerisation. The inactivation of ohr did not affect symbiosis and nitrogen fixation, suggesting that redundant enzymatic activity exists in this strain. Both ohr and ohrR are expressed in nodules suggesting that they play a role during nitrogen fixation. CONCLUSIONS: This report demonstrates the significant role Ohr and OhrR proteins play in bacterial stress resistance against organic peroxides in S. meliloti. The ohr and ohrR genes are expressed in nodule-inhabiting bacteroids suggesting a role during nodulation. | 2011 | 21569462 |
| 608 | 4 | 0.9939 | Entamoeba histolytica Adaption to Auranofin: A Phenotypic and Multi-Omics Characterization. Auranofin (AF), an antirheumatic agent, targets mammalian thioredoxin reductase (TrxR), an important enzyme controlling redox homeostasis. AF is also highly effective against a diversity of pathogenic bacteria and protozoan parasites. Here, we report on the resistance of the parasite Entamoeba histolytica to 2 µM of AF that was acquired by gradual exposure of the parasite to an increasing amount of the drug. AF-adapted E. histolytica trophozoites (AFAT) have impaired growth and cytopathic activity, and are more sensitive to oxidative stress (OS), nitrosative stress (NS), and metronidazole (MNZ) than wild type (WT) trophozoites. Integrated transcriptomics and redoxomics analyses showed that many upregulated genes in AFAT, including genes encoding for dehydrogenase and cytoskeletal proteins, have their product oxidized in wild type trophozoites exposed to AF (acute AF trophozoites) but not in AFAT. We also showed that the level of reactive oxygen species (ROS) and oxidized proteins (OXs) in AFAT is lower than that in acute AF trophozoites. Overexpression of E. histolytica TrxR (EhTrxR) did not protect the parasite against AF, which suggests that EhTrxR is not central to the mechanism of adaptation to AF. | 2021 | 34439488 |
| 603 | 5 | 0.9938 | Transcriptomic Analysis Reveals Adaptive Responses of an Enterobacteriaceae Strain LSJC7 to Arsenic Exposure. Arsenic (As) resistance determinant ars operon is present in many bacteria and has been demonstrated to enhance As(V) resistance of bacteria. However, whole molecular mechanism adaptations of bacteria in response to As(V) stress remain largely unknown. In this study, transcriptional profiles of Enterobacteriaceae strain LSJC7 responding to As(V) stress were analyzed using RNA-seq and qRT-PCR. As expected, genes involved in As(V) uptake were down-regulated, those involved in As(V) reduction and As(III) efflux were up-regulated, which avoided cellular As accumulation. Reactive oxygen species and nitric oxide (NO) were induced, which caused cellular damages including DNA, protein, and Fe-S cluster damage in LSJC7. The expression of specific genes encoding transcriptional regulators, such as nsrR and soxRS were also induced. NsrR and SoxRS modulated many critical metabolic activities in As(V) stressed LSJC7 cells, including reactive species scavenging and repairing damaged DNA, proteins, and Fe-S clusters. Therefore, besides As uptake, reduction, and efflux; oxidative stress defense and damage repair were the main cellular adaptive responses of LSJC7 to As(V) stress. | 2016 | 27199962 |
| 594 | 6 | 0.9938 | Challenging Xanthomonas campestris with low levels of arsenic mediates cross-protection against oxidant killing. Xanthomonas encounters highly toxic reactive oxygen species (ROS) from many sources, such as those generated by plants against invading bacteria, other soil bacteria and from aerobic respiration. Thus, conditions that alter intracellular ROS levels such as exposure to toxic metalloids would have profound effects on bacterial physiology. Here, we report that exposure of Xanthomonas campestris pv. phaseoli (Xp) to low levels of arsenic induces physiological cross-protection against killing by H(2)O(2) and organic hydroperoxide but not a superoxide generator. Cross-protection against H(2)O(2) and organic hydroperoxide toxicity was due to increased expression of genes encoding major peroxide-metabolizing enzymes such as alkyl hydroperoxide reductase (AhpC), catalase (KatA) and organic hydroperoxide resistance protein (Ohr). Arsenic-induced protection against H(2)O(2) and organic hydroperoxide requires the peroxide stress response regulators, OxyR and OhrR, respectively. Moreover, analyses of double mutants of the major H(2)O(2) and organic hyproperoxide-scavenging enzymes, Xp ahpC katA and Xp ahpC ohr, respectively, suggested the existence of unidentified OxyR- and OhrR-regulated genes that are involved in arsenic-induced resistance to H(2)O(2) and organic hyproperoxide killing in Xp. These arsenic-induced physiological alterations could play an important role in bacterial survival both in the soil environment and during plant-pathogen interactions. | 2006 | 16907748 |
| 807 | 7 | 0.9936 | Transcriptomic analysis of Saccharomyces cerevisiae upon honokiol treatment. Honokiol (HNK), one of the main medicinal components in Magnolia officinalis, possesses antimicrobial activity against a variety of pathogenic bacteria and fungi. However, little is known of the molecular mechanisms underpinning the antimicrobial activity. To explore the molecular mechanism of its antifungal activity, we determined the effects of HNK on the mRNA expression profile of Saccharomyces cerevisiae using a DNA microarray approach. HNK markedly induced the expression of genes related to iron uptake and homeostasis. Conversely, genes associated with respiratory electron transport were downregulated, mirroring the effects of iron starvation. Meanwhile, HNK-induced growth deficiency was partly rescued by iron supplementation and HNK reacted with iron, producing iron complexes that depleted iron. These results suggest that HNK treatment induced iron starvation. Additionally, HNK treatment resulted in the upregulation of genes involved in protein synthesis and drug resistance networks. Furthermore, the deletion of PDR5, a gene encoding the plasma membrane ATP binding cassette (ABC) transporter, conferred sensitivity to HNK. Overexpression of PDR5 enhanced resistance of WT and pdr5Δ strains to HNK. Taken together, these findings suggest that HNK, which can be excluded by overexpression of Pdr5, functions in multiple cellular processes in S. cerevisiae, particularly in inducing iron starvation to inhibit cell growth. | 2017 | 28499955 |
| 713 | 8 | 0.9936 | OxyR-activated expression of Dps is important for Vibrio cholerae oxidative stress resistance and pathogenesis. Vibrio cholerae is the causative agent of cholera, a dehydrating diarrheal disease. This Gram-negative pathogen is able to modulate its gene expression in order to combat stresses encountered in both aquatic and host environments, including stress posed by reactive oxygen species (ROS). In order to further the understanding of V. cholerae's transcriptional response to ROS, we performed an RNA sequencing analysis to determine the transcriptional profile of V. cholerae when exposed to hydrogen hydroperoxide. Of 135 differentially expressed genes, VC0139 was amongst the genes with the largest induction. VC0139 encodes a protein homologous to the DPS (DNA-binding protein from starved cells) protein family, which are widely conserved and are implicated in ROS resistance in other bacteria. Using a promoter reporter assay, we show that during exponential growth, dps is induced by H2O2 in a manner dependent on the ROS-sensing transcriptional regulator, OxyR. Upon entry into stationary phase, the major stationary phase regulator RpoS is required to transcribe dps. Deletion of dps impaired V. cholerae resistance to both inorganic and organic hydroperoxides. Furthermore, we show that Dps is involved in resistance to multiple environmental stresses. Finally, we found that Dps is important for V. cholerae adult mouse colonization, but becomes dispensable in the presence of antioxidants. Taken together, our results suggest that Dps plays vital roles in both V. cholerae stress resistance and pathogenesis. | 2017 | 28151956 |
| 583 | 9 | 0.9935 | MarR family proteins sense sulfane sulfur in bacteria. Members of the multiple antibiotic resistance regulator (MarR) protein family are ubiquitous in bacteria and play critical roles in regulating cellular metabolism and antibiotic resistance. MarR family proteins function as repressors, and their interactions with modulators induce the expression of controlled genes. The previously characterized modulators are insufficient to explain the activities of certain MarR family proteins. However, recently, several MarR family proteins have been reported to sense sulfane sulfur, including zero-valent sulfur, persulfide (R-SSH), and polysulfide (R-SnH, n ≥ 2). Sulfane sulfur is a common cellular component in bacteria whose levels vary during bacterial growth. The changing levels of sulfane sulfur affect the expression of many MarR-controlled genes. Sulfane sulfur reacts with the cysteine thiols of MarR family proteins, causing the formation of protein thiol persulfide, disulfide bonds, and other modifications. Several MarR family proteins that respond to reactive oxygen species (ROS) also sense sulfane sulfur, as both sulfane sulfur and ROS induce the formation of disulfide bonds. This review focused on MarR family proteins that sense sulfane sulfur. However, the sensing mechanisms reviewed here may also apply to other proteins that detect sulfane sulfur, which is emerging as a modulator of gene regulation. | 2024 | 38948149 |
| 599 | 10 | 0.9935 | RNase III participates in control of quorum sensing, pigmentation and oxidative stress resistance in Rhodobacter sphaeroides. RNase III is a dsRNA-specific endoribonuclease, highly conserved in bacteria and eukarya. In this study, we analysed the effects of inactivation of RNase III on the transcriptome and the phenotype of the facultative phototrophic α-proteobacterium Rhodobacter sphaeroides. RNA-seq revealed an unexpectedly high amount of genes with increased expression located directly downstream to the rRNA operons. Chromosomal insertion of additional transcription terminators restored wild type-like expression of the downstream genes, indicating that RNase III may modulate the rRNA transcription termination in R. sphaeroides. Furthermore, we identified RNase III as a major regulator of quorum-sensing autoinducer synthesis in R. sphaeroides. It negatively controls the expression of the autoinducer synthase CerI by reducing cerI mRNA stability. In addition, RNase III inactivation caused altered resistance against oxidative stress and impaired formation of photosynthetically active pigment-protein complexes. We also observed an increase in the CcsR small RNAs that were previously shown to promote resistance to oxidative stress. Taken together, our data present interesting insights into RNase III-mediated regulation and expand the knowledge on the function of this important enzyme in bacteria. | 2023 | 37823424 |
| 730 | 11 | 0.9935 | How intracellular bacteria survive: surface modifications that promote resistance to host innate immune responses. Bacterial pathogens regulate the expression of virulence factors in response to environmental signals. In the case of salmonellae, many virulence factors are regulated via PhoP/PhoQ, a two-component signal transduction system that is repressed by magnesium and calcium in vitro. PhoP/PhoQ-activated genes promote intracellular survival within macrophages, whereas PhoP-repressed genes promote entrance into epithelial cells and macrophages by macropinocytosis and stimulate epithelial cell cytokine production. PhoP-activated genes include those that alter the cell envelope through structural alterations of lipopolysaccharide and lipid A, the bioactive component of lipopolysaccharide. PhoP-activated changes in the bacterial envelope likely promote intracellular survival by increasing resistance to host cationic antimicrobial peptides and decreasing host cell cytokine production. | 1999 | 10081503 |
| 726 | 12 | 0.9935 | Regulation of antimicrobial resistance by extracytoplasmic function (ECF) sigma factors. Extracytoplasmic function (ECF) sigma factors are a subfamily of σ(70) sigma factors that activate genes involved in stress-response functions. In many bacteria, ECF sigma factors regulate resistance to antimicrobial compounds. This review will summarize the ECF sigma factors that regulate antimicrobial resistance in model organisms and clinically relevant pathogens. | 2017 | 28153747 |
| 718 | 13 | 0.9935 | Roles of rpoS-activating small RNAs in pathways leading to acid resistance of Escherichia coli. Escherichia coli and related enteric bacteria can survive under extreme acid stress condition at least for several hours. RpoS is a key factor for acid stress management in many enterobacteria. Although three rpoS-activating sRNAs, DsrA, RprA, and ArcZ, have been identified in E. coli, it remains unclear how these small RNA molecules participate in pathways leading to acid resistance (AR). Here, we showed that overexpression of ArcZ, DsrA, or RprA enhances AR in a RpoS-dependent manner. Mutant strains with deletion of any of three sRNA genes showed lowered AR, and deleting all three sRNA genes led to more severe defects in protecting against acid stress. Overexpression of any of the three sRNAs fully rescued the acid tolerance defects of the mutant strain lacking all three genes, suggesting that all three sRNAs perform the same function in activating RpoS required for AR. Notably, acid stress led to the induction of DsrA and RprA but not ArcZ. | 2014 | 24319011 |
| 88 | 14 | 0.9934 | Constitutive expression of mammalian nitric oxide synthase in tobacco plants triggers disease resistance to pathogens. Nitric oxide (NO) is known for its role in the activation of plant defense responses. To examine the involvement and mode of action of NO in plant defense responses, we introduced calmodulin-dependent mammalian neuronal nitric oxide synthase (nNOS), which controls the CaMV35S promoter, into wild-type and NahG tobacco plants. Constitutive expression of nNOS led to NO production and triggered spontaneous induction of leaf lesions. Transgenic plants accumulated high amounts of H(2)O(2), with catalase activity lower than that in the wild type. nNOS transgenic plants contained high levels of salicylic acid (SA), and they induced an array of SA-, jasmonic acid (JA)-, and/or ethylene (ET)-related genes. Consequently, NahG co-expression blocked the induction of systemic acquired resistance (SAR)-associated genes in transgenic plants, implying SA is involved in NO-mediated induction of SAR genes. The transgenic plants exhibited enhanced resistance to a spectrum of pathogens, including bacteria, fungi, and viruses. Our results suggest a highly ranked regulatory role for NO in SA-, JA-, and/or ET-dependent pathways that lead to disease resistance. | 2012 | 23124383 |
| 668 | 15 | 0.9934 | c-di-GMP regulates the resistance of Pseudomonas aeruginosa to heat shock and aminoglycoside antibiotics by targeting the σ factor RpoH. Cyclic di-GMP (c-di-GMP) is a second messenger molecule that is widely distributed in bacteria and plays various physiologically important regulatory roles through interactions with a variety of effector molecules. Sigma (σ) factors are the predominant transcription factors involved in transcription regulation in bacteria. While c-di-GMP has been shown to bind to a range of transcription factors, c-di-GMP-binding σ factors have never been reported before. In a c-di-GMP/σ factors binding screen, we identified the σ factor RpoH as a c-di-GMP-responsive transcription factor in Pseudomonas aeruginosa PAO1. We further show that the binding of c-di-GMP to RpoH inhibits binding of RpoH to the promoters of its target genes such as asrA and dnaK, thereby downregulating the expression of these genes and reducing the resistance of P. aeruginosa to heat shock and aminoglycoside antibiotics. RpoH from Escherichia coli, Burkholderia thailandensis and Agrobacterium tumefaciens are also capable of binding c-di-GMP, suggesting that c-di-GMP-mediated control of the activity of RpoH is conserved in members of Proteobacteria. | 2026 | 41005124 |
| 604 | 16 | 0.9934 | Redox signaling and gene control in the Escherichia coli soxRS oxidative stress regulon--a review. The soxRS regulon of Escherichia coli coordinates the induction of at least twelve genes in response to superoxide or nitric oxide. This review describes recent progress in understanding the signal transduction and transcriptional control mechanisms that activate the soxRS regulon, and some aspects of the physiological functions of this system. The SoxS protein represents a growing family of transcription activators that stimulate genes for resistance to oxidative stress and antibiotics. SoxR is an unusual transcription factor whose activity in vitro can be switched off by the removal of [2Fe-2S] centers, and activated by their reinsertion. The activated form of SoxR remodels the structure of the soxS promoter to activate transcription. When the soxRS system is activated, bacteria gain resistance to oxidants, antibiotics and immune cells that generate nitric oxide. The latter features could increase the success (virulence) of some bacterial infections. | 1996 | 8955629 |
| 8348 | 17 | 0.9934 | Role of RelA-synthesized (p)ppGpp and ROS-induced mutagenesis in de novo acquisition of antibiotic resistance in E. coli. The stringent response of bacteria to starvation and stress also fulfills a role in addressing the threat of antibiotics. Within this stringent response, (p)ppGpp, synthesized by RelA or SpoT, functions as a global alarmone. However, the effect of this (p)ppGpp on resistance development is poorly understood. Here, we show that knockout of relA or rpoS curtails resistance development against bactericidal antibiotics. The emergence of mutated genes associated with starvation and (p)ppGpp, among others, indicates the activation of stringent responses. The growth rate is decreased in ΔrelA-resistant strains due to the reduced ability to synthesize (p)ppGpp and the persistence of deacylated tRNA impeding protein synthesis. Sluggish cellular activity causes decreased production of reactive oxygen species (ROS), thereby reducing oxidative damage, leading to weakened DNA mismatch repair, potentially reducing the generation of mutations. These findings offer new targets for mitigating antibiotic resistance development, potentially achieved through inhibiting (p)ppGpp or ROS synthesis. | 2024 | 38617560 |
| 754 | 18 | 0.9933 | Resistance to Bipyridyls Mediated by the TtgABC Efflux System in Pseudomonas putida KT2440. Resistance-nodulation-division (RND) transporters are involved in antibiotic resistance and have a broad substrate specificity. However, the physiological significance of these efflux pumps is not fully understood. Here, we have investigated the role of the RND system TtgABC in resistance to metal ion chelators in the soil bacterium Pseudomonas putida KT2440. We observed that the combined action of an RND inhibitor and the chelator 2,2'-bipyridyl inhibited bacterial growth. In addition, the deletion of ttgB made the strain susceptible to 2,2'-bipyridyl and natural bipyridyl derivatives such as caerulomycin A, indicating that TtgABC is required for detoxification of compounds of the bipyridyl family. Searching for the basis of growth inhibition by bipyridyls, we found reduced adenosine triphosphate (ATP) levels in the ttgB mutant compared to the wild type. Furthermore, the expression of genes related to iron acquisition and the synthesis of the siderophore pyoverdine were reduced in the mutant compared to the wild type. Investigating the possibility that 2,2'-bipyridyl in the ttgB mutant mediates iron accumulation in cells (which would cause the upregulation of genes involved in oxidative stress via the Fenton reaction), we measured the expression of genes coding for proteins involved in intracellular iron storage and the response to oxidative stress. However, none of the genes was significantly upregulated. In a further search for a possible link between 2,2'-bipyridyl and the observed phenotypes, we considered the possibility that the ion chelator limits the intracellular availability of metabolically important metal ions. In this context, we found that the addition of copper restores the growth of the ttgB mutant and the production of pyoverdine, suggesting a relationship between copper availability and iron acquisition. Taken together, the results suggest that detoxification of metal chelating compounds of the bipyridyl family produced by other bacteria or higher ordered organisms is one of the native functions of the RND efflux pump TtgABC. Without the efflux pump, these compounds may interfere with cell ion homeostasis with adverse effects on cell metabolism, including siderophore production. Finally, our results suggest that TtgABC is involved in resistance to bile salts and deoxycholate. | 2020 | 32973714 |
| 722 | 19 | 0.9933 | Evolution of Escherichia coli for maximum HOCl resistance through constitutive expression of the OxyR regulon. Exposure of cells to stress impairs cellular functions and may cause killing or adaptation. Adaptation can be facilitated by stress-induced mutagenesis or epigenetic changes, i.e. phenotypic variation without mutations. Upon exposure to HOCl, which is produced by the innate immune system upon bacterial infection, bacteria trigger stress responses that enable increased survival against the stress. Here, we addressed the question whether bacteria can adapt to high HOCl doses and if so, how the acquired resistance is facilitated. We evolved Escherichia coli cells for maximum HOCl resistance by successively increasing the HOCl concentration in the cultivation medium. HOCl-resistant cells showed broad stress resistance but did not carry any chromosomal mutations as revealed by whole-genome sequencing. According to proteome analysis and analysis of transcript levels of stress-related genes, HOCl resistance was accompanied by altered levels of outer-membrane proteins A, C, F and W, and, most prominently, a constitutively expressed OxyR regulon. Induction of the OxyR regulon is facilitated by a partially oxidized OxyR leading to increased levels of antioxidant proteins such as Dps, AhpC/AhpF and KatG. These changes were maintained in evolved strains even when they were cultivated without stress for a prolonged time, indicating epigenetic changes contributed to stress resistance. This indicated that maximum HOCl resistance was conferred by the accumulated action of the OxyR stress response and other factors such as altered levels of outer-membrane proteins. | 2014 | 24899627 |