# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 8283 | 0 | 0.9943 | Stress responses as determinants of antimicrobial resistance in Gram-negative bacteria. Bacteria encounter a myriad of potentially growth-compromising conditions in nature and in hosts of pathogenic bacteria. These 'stresses' typically elicit protective and/or adaptive responses that serve to enhance bacterial survivability. Because they impact upon many of the same cellular components and processes that are targeted by antimicrobials, adaptive stress responses can influence antimicrobial susceptibility. In targeting and interfering with key cellular processes, antimicrobials themselves are 'stressors' to which protective stress responses have also evolved. Cellular responses to nutrient limitation (nutrient stress), oxidative and nitrosative stress, cell envelope damage (envelope stress), antimicrobial exposure and other growth-compromising stresses, have all been linked to the development of antimicrobial resistance in Gram-negative bacteria - resulting from the stimulation of protective changes to cell physiology, activation of resistance mechanisms, promotion of resistant lifestyles (biofilms), and induction of resistance mutations. | 2012 | 22424589 |
| 8190 | 1 | 0.9943 | Identification of Quorum-Sensing Inhibitors Disrupting Signaling between Rgg and Short Hydrophobic Peptides in Streptococci. Bacteria coordinate a variety of social behaviors, important for both environmental and pathogenic bacteria, through a process of intercellular chemical signaling known as quorum sensing (QS). As microbial resistance to antibiotics grows more common, a critical need has emerged to develop novel anti-infective therapies, such as an ability to attenuate bacterial pathogens by means of QS interference. Rgg quorum-sensing pathways, widespread in the phylum Firmicutes, employ cytoplasmic pheromone receptors (Rgg transcription factors) that directly bind and elicit gene expression responses to imported peptide signals. In the human-restricted pathogen Streptococcus pyogenes, the Rgg2/Rgg3 regulatory circuit controls biofilm development in response to the short hydrophobic peptides SHP2 and SHP3. Using Rgg-SHP as a model receptor-ligand target, we sought to identify chemical compounds that could specifically inhibit Rgg quorum-sensing circuits. Individual compounds from a diverse library of known drugs and drug-like molecules were screened for their ability to disrupt complexes of Rgg and FITC (fluorescein isothiocyanate)-conjugated SHP using a fluorescence polarization (FP) assay. The best hits were found to bind Rgg3 in vitro with submicromolar affinities, to specifically abolish transcription of Rgg2/3-controlled genes, and to prevent biofilm development in S. pyogenes without affecting bacterial growth. Furthermore, the top hit, cyclosporine A, as well as its nonimmunosuppressive analog, valspodar, inhibited Rgg-SHP pathways in multiple species of Streptococcus. The Rgg-FITC-peptide-based screen provides a platform to identify inhibitors specific for each Rgg type. Discovery of Rgg inhibitors constitutes a step toward the goal of manipulating bacterial behavior for purposes of improving health. IMPORTANCE: The global emergence of antibiotic-resistant bacterial infections necessitates discovery not only of new antimicrobials but also of novel drug targets. Since antibiotics restrict microbial growth, strong selective pressures to develop resistance emerge quickly in bacteria. A new strategy to fight microbial infections has been proposed, namely, development of therapies that decrease pathogenicity of invading organisms while not directly inhibiting their growth, thus decreasing selective pressure to establish resistance. One possible means to this goal is to interfere with chemical communication networks used by bacteria to coordinate group behaviors, which can include the synchronized expression of genes that lead to disease. In this study, we identified chemical compounds that disrupt communication pathways regulated by Rgg proteins in species of Streptococcus. Treatment of cultures of S. pyogenes with the inhibitors diminished the development of biofilms, demonstrating an ability to control bacterial behavior with chemicals that do not inhibit growth. | 2015 | 25968646 |
| 9169 | 2 | 0.9942 | Interference of bacterial cell-to-cell communication: a new concept of antimicrobial chemotherapy breaks antibiotic resistance. Bacteria use a cell-to-cell communication activity termed "quorum sensing" to coordinate group behaviors in a cell density dependent manner. Quorum sensing influences the expression profile of diverse genes, including antibiotic tolerance and virulence determinants, via specific chemical compounds called "autoinducers". During quorum sensing, Gram-negative bacteria typically use an acylated homoserine lactone (AHL) called autoinducer 1. Since the first discovery of quorum sensing in a marine bacterium, it has been recognized that more than 100 species possess this mechanism of cell-to-cell communication. In addition to being of interest from a biological standpoint, quorum sensing is a potential target for antimicrobial chemotherapy. This unique concept of antimicrobial control relies on reducing the burden of virulence rather than killing the bacteria. It is believed that this approach will not only suppress the development of antibiotic resistance, but will also improve the treatment of refractory infections triggered by multi-drug resistant pathogens. In this paper, we review and track recent progress in studies on AHL inhibitors/modulators from a biological standpoint. It has been discovered that both natural and synthetic compounds can disrupt quorum sensing by a variety of means, such as jamming signal transduction, inhibition of signal production and break-down and trapping of signal compounds. We also focus on the regulatory elements that attenuate quorum sensing activities and discuss their unique properties. Understanding the biological roles of regulatory elements might be useful in developing inhibitor applications and understanding how quorum sensing is controlled. | 2013 | 23720655 |
| 766 | 3 | 0.9942 | The essential inner membrane protein YejM is a metalloenzyme. Recent recurrent outbreaks of Gram-negative bacteria show the critical need to target essential bacterial mechanisms to fight the increase of antibiotic resistance. Pathogenic Gram-negative bacteria have developed several strategies to protect themselves against the host immune response and antibiotics. One such strategy is to remodel the outer membrane where several genes are involved. yejM was discovered as an essential gene in E. coli and S. typhimurium that plays a critical role in their virulence by changing the outer membrane permeability. How the inner membrane protein YejM with its periplasmic domain changes membrane properties remains unknown. Despite overwhelming structural similarity between the periplasmic domains of two YejM homologues with hydrolases like arylsulfatases, no enzymatic activity has been previously reported for YejM. Our studies reveal an intact active site with bound metal ions in the structure of YejM periplasmic domain. Furthermore, we show that YejM has a phosphatase activity that is dependent on the presence of magnesium ions and is linked to its function of regulating outer membrane properties. Understanding the molecular mechanism by which YejM is involved in outer membrane remodeling will help to identify a new drug target in the fight against the increased antibiotic resistance. | 2020 | 33082366 |
| 604 | 4 | 0.9942 | 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 |
| 9525 | 5 | 0.9941 | Is there a serious risk of resistance development to azoles among fungi due to the widespread use and long-term application of azole antifungals in medicine? It is well known that development of antibiotic resistance in bacteria is not a matter of if but of when. Recently, azoles have been recommended for long-term prophylaxis of invasive fungal infections; hence, it could be argued that fungi also will become resistant to these agents. However, fungi are different from bacteria in several critical points. Bacteria display several resistance mechanisms: alteration of the target, limited access to the target and modification/inactivation of the antibacterial compound. In fungi some mechanisms of resistance to azoles are also known; with azoles for example, alterations of the 14alpha-demethylase target, as well as efflux pumps. It has been observed that these phenotypes develop in yeast populations either due to mutations or to selection processes. However, enzymes which destroy azoles are not found. Furthermore, a horizontal transfer of genes coding resistance traits does not occur in fungi, which means that an explosive expansion of resistances is unlikely to occur, especially in moulds. Indeed, in epidemiologic studies on human and environmental isolates there is convincing evidence that azole resistance is quite uncommon. | 2008 | 18325827 |
| 8290 | 6 | 0.9941 | Antimicrobial Peptides: Features, Action, and Their Resistance Mechanisms in Bacteria. In recent years, because of increased resistance to conventional antimicrobials, many researchers have started to study the synthesis of new antibiotics to control the disease-causing effects of infectious pathogens. Antimicrobial peptides (AMPs) are among the newest antibiotics; these peptides are integral compounds in all kinds of organisms and play a significant role in microbial ecology, and critically contribute to the innate immunity of organisms by destroying invading microorganisms. Moreover, AMPs may encourage cells to produce chemokines, stimulate angiogenesis, accelerate wound healing, and influence programmed cell death in multicellular organisms. Bacteria differ in their inherent susceptibility and resistance mechanisms to these peptides when responding to the antimicrobial effects of AMPs. Generally, the development of AMP resistance mechanisms is driven by direct competition between bacterial species, and host and pathogen interactions. Several studies have shown diverse mechanisms of bacterial resistance to AMPs, for example, some bacteria produce proteases and trapping proteins; some modify cell surface charge, change membrane fluidity, and activate efflux pumps; and some species make use of biofilms and exopolymers, and develop sensing systems by selective gene expression. A closer understanding of bacterial resistance mechanisms may help in developing novel therapeutic approaches for the treatment of infections caused by pathogenic organisms that are successful in developing extensive resistance to AMPs. Based on these observations, this review discusses the properties of AMPs, their targeting mechanisms, and bacterial resistance mechanisms against AMPs. | 2018 | 29957118 |
| 8347 | 7 | 0.9941 | Molecular mechanisms underlying glyphosate resistance in bacteria. Glyphosate is a nonselective herbicide that kills weeds and other plants competing with crops. Glyphosate specifically inhibits the 5-enolpyruvyl-shikimate-3-phosphate (EPSP) synthase, thereby depleting the cell of EPSP serving as a precursor for biosynthesis of aromatic amino acids. Glyphosate is considered to be toxicologically safe for animals and humans. Therefore, it became the most-important herbicide in agriculture. However, its intensive application in agriculture is a serious environmental issue because it may negatively affect the biodiversity. A few years after the discovery of the mode of action of glyphosate, it has been observed that bacteria evolve glyphosate resistance by acquiring mutations in the EPSP synthase gene, rendering the encoded enzyme less sensitive to the herbicide. The identification of glyphosate-resistant EPSP synthase variants paved the way for engineering crops tolerating increased amounts of the herbicide. This review intends to summarize the molecular mechanisms underlying glyphosate resistance in bacteria. Bacteria can evolve glyphosate resistance by (i) reducing glyphosate sensitivity or elevating production of the EPSP synthase, by (ii) degrading or (iii) detoxifying glyphosate and by (iv) decreasing the uptake or increasing the export of the herbicide. The variety of glyphosate resistance mechanisms illustrates the adaptability of bacteria to anthropogenic substances due to genomic alterations. | 2021 | 33876549 |
| 8289 | 8 | 0.9941 | Roles of Regulatory RNAs for Antibiotic Resistance in Bacteria and Their Potential Value as Novel Drug Targets. The emergence of antibiotic resistance mechanisms among bacterial pathogens increases the demand for novel treatment strategies. Lately, the contribution of non-coding RNAs to antibiotic resistance and their potential value as drug targets became evident. RNA attenuator elements in mRNA leader regions couple expression of resistance genes to the presence of the cognate antibiotic. Trans-encoded small RNAs (sRNAs) modulate antibiotic tolerance by base-pairing with mRNAs encoding functions important for resistance such as metabolic enzymes, drug efflux pumps, or transport proteins. Bacteria respond with extensive changes of their sRNA repertoire to antibiotics. Each antibiotic generates a unique sRNA profile possibly causing downstream effects that may help to overcome the antibiotic challenge. In consequence, regulatory RNAs including sRNAs and their protein interaction partners such as Hfq may prove useful as targets for antimicrobial chemotherapy. Indeed, several compounds have been developed that kill bacteria by mimicking ligands for riboswitches controlling essential genes, demonstrating that regulatory RNA elements are druggable targets. Drugs acting on sRNAs are considered for combined therapies to treat infections. In this review, we address how regulatory RNAs respond to and establish resistance to antibiotics in bacteria. Approaches to target RNAs involved in intrinsic antibiotic resistance or virulence for chemotherapy will be discussed. | 2017 | 28529506 |
| 733 | 9 | 0.9941 | Transcription Factor PecS Mediates Agrobacterium fabrum Fitness and Survival. The transcriptional regulator PecS is encoded by select bacterial pathogens. For instance, in the plant pathogen Dickeya dadantii, PecS controls a range of virulence genes, including pectinase genes and the divergently oriented gene pecM, which encodes an efflux pump through which the antioxidant indigoidine is exported. In the plant pathogen Agrobacterium fabrum (formerly named Agrobacterium tumefaciens), the pecS-pecM locus is conserved. Using a strain of A. fabrum in which pecS has been disrupted, we show here that PecS controls a range of phenotypes that are associated with bacterial fitness. PecS represses flagellar motility and chemotaxis, which are processes that are important for A. fabrum to reach plant wound sites. Biofilm formation and microaerobic survival are reduced in the pecS disruption strain, whereas the production of acyl homoserine lactone (AHL) and resistance to reactive oxygen species (ROS) are increased when pecS is disrupted. AHL production and resistance to ROS are expected to be particularly relevant in the host environment. We also show that PecS does not participate in the induction of vir genes. The inducing ligands for PecS, urate, and xanthine, may be found in the rhizosphere, and they accumulate within the plant host upon infection. Therefore, our data suggest that PecS mediates A. fabrum fitness during its transition from the rhizosphere to the host plant. IMPORTANCE PecS is a transcription factor that is conserved in several pathogenic bacteria, where it regulates virulence genes. The plant pathogen Agrobacterium fabrum is important not only for its induction of crown galls in susceptible plants but also for its role as a tool in the genetic manipulation of host plants. We show here that A. fabrum PecS controls a range of phenotypes, which would confer the bacteria an advantage while transitioning from the rhizosphere to the host plant. This includes the production of signaling molecules, which are critical for the propagation of the tumor-inducing plasmid. A more complete understanding of the infection process may inform approaches by which to treat infections as well as to facilitate the transformation of recalcitrant plant species. | 2023 | 37314346 |
| 8144 | 10 | 0.9941 | Fungal Priming: Prepare or Perish. Priming (also referred to as acclimation, acquired stress resistance, adaptive response, or cross-protection) is defined as an exposure of an organism to mild stress that leads to the development of a subsequent stronger and more protective response. This memory of a previously encountered stress likely provides a strong survival advantage in a rapidly shifting environment. Priming has been identified in animals, plants, fungi, and bacteria. Examples include innate immune priming and transgenerational epigenetic inheritance in animals and biotic and abiotic stress priming in plants, fungi, and bacteria. Priming mechanisms are diverse and include alterations in the levels of specific mRNAs, proteins, metabolites, and epigenetic changes such as DNA methylation and histone acetylation of target genes. | 2022 | 35628704 |
| 757 | 11 | 0.9940 | Regulation of antibiotic-resistance by non-coding RNAs in bacteria. Antibiotic resistance genes are commonly regulated by sophisticated mechanisms that activate gene expression in response to antibiotic exposure. Growing evidence suggest that cis-acting non-coding RNAs play a major role in regulating the expression of many resistance genes, specifically those which counteract the effects of translation-inhibiting antibiotics. These ncRNAs reside in the 5'UTR of the regulated gene, and sense the presence of the antibiotics by recruiting translating ribosomes onto short upstream open reading frames (uORFs) embedded in the ncRNA. In the presence of translation-inhibiting antibiotics ribosomes arrest over the uORF, altering the RNA structure of the regulator and switching the expression of the resistance gene to 'ON'. The specificity of these riboregulators is tuned to sense-specific classes of antibiotics based on the length and composition of the respective uORF. Here we review recent work describing new types of antibiotic-sensing RNA-based regulators and elucidating the molecular mechanisms by which they function to control antibiotic resistance in bacteria. | 2017 | 28414973 |
| 8322 | 12 | 0.9940 | Pathogen-induced damage in Drosophila: Uncoupling disease tolerance from resistance. Immune response against infections can be divided into mechanisms of resistance that ensure active pathogen elimination, and mechanisms of disease tolerance, which include processes that return the host to physiological homeostasis without direct control of pathogen load. Studies on host immune response to infection have targeted mechanisms of resistance, and consequently, these are now well-described in both vertebrates and invertebrates. By comparison, the mechanistic basis of disease tolerance is poorly understood. This is in part because both processes interact and can be difficult to disentangle under an infection scenario. Using the insect model Drosophila melanogaster exposed to its natural entomopathogen, Pseudomonas entomophila, we aimed to tease apart mechanisms of disease tolerance from those of resistance. To this end, we reasoned that the response to oral exposure to heat-killed entomopathogenic bacteria, whilst initially triggering both resistance and disease tolerance mechanisms, would be resolved mainly by disease tolerance alone. Using this method, we observe that oral exposure to heat-killed P. entomophila causes mortality and reduced fecundity in D. melanogaster. We confirm that this reduction in fitness-related traits depends on the duration of the exposure, is sexually dimorphic, and is dependent on the virulence of the bacterium. We also found the microbiota to play a role, with its presence exacerbating the deleterious effect on host survival. In addition, we show that the Imd pathway, but not effector genes, is involved in the process of surviving exposure to HK bacteria. This experimental framework, which may be extended to other systems, can be instrumental towards an understanding of the molecular, genetic, and physiological basis of disease tolerance and its interactions with resistance mechanisms. | 2025 | 40971962 |
| 9065 | 13 | 0.9940 | Gut Bacteria Promote Phosphine Susceptibility of Tribolium castaneum by Aggravating Oxidative Stress and Fitness Costs. Knowledge about resistance mechanisms can provide ideas for pesticide resistance management. Although several studies have unveiled the positive or negative impacts of gut microbes on host pesticide resistance, minimal research is available regarding the association between gut microbes and host phosphine resistance. To explore the influence of gut bacteria on host phosphine susceptibility and its molecular basis, mortality, fitness, redox responses, and immune responses of adult Tribolium castaneum were determined when it was challenged by phosphine exposure and/or gut bacteria inoculation. Five cultivable gut bacteria were excised from a population of phosphine-resistant T. castaneum. Among them, only Enterococcus sp. inoculation significantly promoted host susceptibility to phosphine, while inoculation of any other gut bacteria had no significant effect on host phosphine susceptibility. Furthermore, when T. castaneum was exposed to phosphine, Enterococcus sp. inoculation decreased the female fecundity, promoted host oxidative stress, and suppressed the expression and activity of host superoxide dismutase, catalase, and peroxidase. In the absence of phosphine, Enterococcus sp. inoculation also elicited overactive immune responses in T. castaneum, including the immune deficiency and Toll signaling pathways and the dual oxidase-reactive oxygen species system. These results indicate that Enterococcus sp. likely promotes host phosphine susceptibility by aggravating oxidative stress and fitness costs. | 2023 | 37887827 |
| 8337 | 14 | 0.9940 | Dynamic Boolean modelling reveals the influence of energy supply on bacterial efflux pump expression. Antimicrobial resistance (AMR) is a global health issue. One key factor contributing to AMR is the ability of bacteria to export drugs through efflux pumps, which relies on the ATP-dependent expression and interaction of several controlling genes. Recent studies have shown that significant cell-to-cell ATP variability exists within clonal bacterial populations, but the contribution of intrinsic cell-to-cell ATP heterogeneity is generally overlooked in understanding efflux pumps. Here, we consider how ATP variability influences gene regulatory networks controlling expression of efflux pump genes in two bacterial species. We develop and apply a generalizable Boolean modelling framework, developed to incorporate the dependence of gene expression dynamics on available cellular energy supply. Theoretical results show that differences in energy availability can cause pronounced downstream heterogeneity in efflux gene expression. Cells with higher energy availability have a superior response to stressors. Furthermore, in the absence of stress, model bacteria develop heterogeneous pulses of efflux pump gene expression which contribute to a sustained sub-population of cells with increased efflux expression activity, potentially conferring a continuous pool of intrinsically resistant bacteria. This modelling approach thus reveals an important source of heterogeneity in cell responses to antimicrobials and sheds light on potentially targetable aspects of efflux pump-related antimicrobial resistance. | 2022 | 35078338 |
| 758 | 15 | 0.9940 | Term-seq reveals abundant ribo-regulation of antibiotics resistance in bacteria. Riboswitches and attenuators are cis-regulatory RNA elements, most of which control bacterial gene expression via metabolite-mediated, premature transcription termination. We developed an unbiased experimental approach for genome-wide discovery of such ribo-regulators in bacteria. We also devised an experimental platform that quantitatively measures the in vivo activity of all such regulators in parallel and enables rapid screening for ribo-regulators that respond to metabolites of choice. Using this approach, we detected numerous antibiotic-responsive ribo-regulators that control antibiotic resistance genes in pathogens and in the human microbiome. Studying one such regulator in Listeria monocytogenes revealed an attenuation mechanism mediated by antibiotic-stalled ribosomes. Our results expose broad roles for conditional termination in regulating antibiotic resistance and provide a tool for discovering riboswitches and attenuators that respond to previously unknown ligands. | 2016 | 27120414 |
| 9167 | 16 | 0.9940 | Bioactive proteins from Solanaceae as quorum sensing inhibitors against virulence in Pseudomonas aeruginosa. Cell-to-cell communication or quorum sensing (QS) is a generic event in bacteria that is used to coordinate gene expression among local populations. The phenomenon of QS depends on the fact that presence of sufficient bacteria ascertains a threshold level of autoinducer concentration that allows bacteria to sense a critical cell mass and to activate or repress target genes. Thus, QS has been an attractive target for the development of anti-infective strategies that are not based on the use of antibiotics. Several anti-QS approaches have been demonstrated including natural products from plant-based secondary metabolites. However, the role of plant bioactive proteins as an anti-QS peptide is yet to be deciphered. Against a backdrop of ever-increasing antibiotic resistant pathogens, there is a strong need for development of alternative therapeutic strategies. Thus, our hypothesis is that bioactive proteins from the plant family Solanaceae are quorum quenching molecules that can be exploited to develop a therapeutic strategy against virulence. We presume that bioactive proteins will inactivate or inhibit or degrade QS signals from bacteria to prevent cell-to-cell communication and thus inhibit development of virulence in Pseudomonas aeruginosa. Further, the use of proteins as quorum quenchers will delay the bacteria to develop resistance against these quenching molecules. | 2015 | 25777471 |
| 8305 | 17 | 0.9939 | Light Modulates Metabolic Pathways and Other Novel Physiological Traits in the Human Pathogen Acinetobacter baumannii. Light sensing in chemotrophic bacteria has been relatively recently ascertained. In the human pathogen Acinetobacter baumannii, light modulates motility, biofilm formation, and virulence through the blue-light-sensing-using flavin (BLUF) photoreceptor BlsA. In addition, light can induce a reduction in susceptibility to certain antibiotics, such as minocycline and tigecycline, in a photoreceptor-independent manner. In this work, we identified new traits whose expression levels are modulated by light in this pathogen, which comprise not only important determinants related to pathogenicity and antibiotic resistance but also metabolic pathways, which represents a novel concept for chemotrophic bacteria. Indeed, the phenylacetic acid catabolic pathway and trehalose biosynthesis were modulated by light, responses that completely depend on BlsA. We further show that tolerance to some antibiotics and modulation of antioxidant enzyme levels are also influenced by light, likely contributing to bacterial persistence in adverse environments. Also, we present evidence indicating that surfactant production is modulated by light. Finally, the expression of whole pathways and gene clusters, such as genes involved in lipid metabolism and genes encoding components of the type VI secretion system, as well as efflux pumps related to antibiotic resistance, was differentially induced by light. Overall, our results indicate that light modulates global features of the A. baumannii lifestyle.IMPORTANCE The discovery that nonphototrophic bacteria respond to light constituted a novel concept in microbiology. In this context, we demonstrated that light could modulate aspects related to bacterial virulence, persistence, and resistance to antibiotics in the human pathogen Acinetobacter baumannii In this work, we present the novel finding that light directly regulates metabolism in this chemotrophic bacterium. Insights into the mechanism show the involvement of the photoreceptor BlsA. In addition, tolerance to antibiotics and catalase levels are also influenced by light, likely contributing to bacterial persistence in adverse environments, as is the expression of the type VI secretion system and efflux pumps. Overall, a profound influence of light on the lifestyle of A. baumannii is suggested to occur. | 2017 | 28289081 |
| 8796 | 18 | 0.9939 | Divergent Roles of Escherichia Coli Encoded Lon Protease in Imparting Resistance to Uncouplers of Oxidative Phosphorylation: Roles of marA, rob, soxS and acrB. Uncouplers of oxidative phosphorylation dissipate the proton gradient, causing lower ATP production. Bacteria encounter several non-classical uncouplers in the environment, leading to stress-induced adaptations. Here, we addressed the molecular mechanisms responsible for the effects of uncouplers in Escherichia coli. The expression and functions of genes involved in phenotypic antibiotic resistance were studied using three compounds: two strong uncouplers, i.e., Carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and 2,4-Dinitrophenol (DNP), and one moderate uncoupler, i.e., Sodium salicylate (NaSal). Quantitative expression studies demonstrated induction of transcripts encoding marA, soxS and acrB with NaSal and DNP, but not CCCP. Since MarA and SoxS are degraded by the Lon protease, we investigated the roles of Lon using a lon-deficient strain (Δlon). Compared to the wild-type strain, Δlon shows compromised growth upon exposure to NaSal or 2, 4-DNP. This sensitivity is dependent on marA but not rob and soxS. On the other hand, the Δlon strain shows enhanced growth in the presence of CCCP, which is dependent on acrB. Interestingly, NaSal and 2,4-DNP, but not CCCP, induce resistance to antibiotics, such as ciprofloxacin and tetracycline. This study addresses the effects of uncouplers and the roles of genes involved during bacterial growth and phenotypic antibiotic resistance. Strong uncouplers are often used to treat wastewater, and these results shed light on the possible mechanisms by which bacteria respond to uncouplers. Also, the rampant usage of some uncouplers to treat wastewater may lead to the development of antibiotic resistance. | 2024 | 38372817 |
| 9171 | 19 | 0.9939 | Small molecules modulating AHL-based quorum sensing to attenuate bacteria virulence and biofilms as promising antimicrobial drugs. Clinically significant antibiotic resistance is one of the greatest challenges of the twenty-first century. Yet new antibiotics are currently being developed at a much slower pace than our growing need for such drugs. Instead of focusing on conventional therapeutics that target in vitro bacterial viability, an alternative therapy is to target virulence factors and biofilms. Such anti-virulence strategies have attracted more and more attention recently, for it would add both supplement and diversity to our current antimicrobial library. This approach has several potential advantages including imposing less evolutionary pressure on the development of antibiotic resistance, increasing the antibacterial targets and preserving the host endogenous microbiome. Quorum sensing is an intercellular communication process in bacterial communities, which can regulate coordinated expression of virulence factors and biofilms. N-Acyl homoserine lactones (AHLs) are autoinducers generated by a variety of Gram-negative bacteria. These signals combining with their cognate LuxR-type receptors trigger the expression of virulence genes. In this critical review, we summarize various structural types of small molecules targeting AHL-based quorum sensing to attenuate bacteria virulence factors and biofilms. | 2014 | 24164200 |