# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 109 | 0 | 1.0000 | Identification of two putative ATP-cassette genes in Encephalitozoon intestinalis. Currently existing chemotherapeutic compounds are limited and few are effective for treating microsporidiosis. It is possible that resistance of Encephalitozoon to some drugs occurs by efflux mechanisms similar to those previously described for mammalian tumour cells, bacteria or protozoal parasites such as Plasmodium, Leishmania and Entamoeba histolytica. The data in the present study suggest that Encephalitozoon intestinalis contains at least one multidrug resistance gene. We report here two complete sequences EiABC1 and EiABC2, encoding different ATP-binding cassette genes from E. intestinalis, including a P-gp. | 2001 | 11730796 |
| 231 | 1 | 0.9981 | Lincosamides, Streptogramins, Phenicols, and Pleuromutilins: Mode of Action and Mechanisms of Resistance. Lincosamides, streptogramins, phenicols, and pleuromutilins (LSPPs) represent four structurally different classes of antimicrobial agents that inhibit bacterial protein synthesis by binding to particular sites on the 50S ribosomal subunit of the ribosomes. Members of all four classes are used for different purposes in human and veterinary medicine in various countries worldwide. Bacteria have developed ways and means to escape the inhibitory effects of LSPP antimicrobial agents by enzymatic inactivation, active export, or modification of the target sites of the agents. This review provides a comprehensive overview of the mode of action of LSPP antimicrobial agents as well as of the mutations and resistance genes known to confer resistance to these agents in various bacteria of human and animal origin. | 2016 | 27549310 |
| 285 | 2 | 0.9981 | Streptothricin resistance as a novel selectable marker for transgenic plant cells.  Streptothricins are known as antimicrobial agents produced by Streptomyces spp. Bacterial resistance to streptothricin is mediated by specific enzymes exhibiting an acetyltransferase activity which renders the drug non-toxic for bacteria. The nucleotide sequence of several streptothricin resistance genes from bacteria have been described. Certain cells of eukaryotic parasites (such as Ustilago maydis or Leishmania spp.) are sensitive to streptothricin and the introduction of the bacterial resistance gene sat2 renders them resistant. We show that numerous species of plants are sensitive to low concentrations of streptothricin. Moreover, introduction of the bacterial resistance gene sat3 under the control of the 35S cauliflower mosaic virus promoter protects these cells from the toxic action of streptothricin. Therefore, sat3-mediated streptothricin resistance appears to be a promising selective marker for genetic manipulation of plant cells. | 2000 | 30754912 |
| 562 | 3 | 0.9980 | Macrolones target bacterial ribosomes and DNA gyrase and can evade resistance mechanisms. Growing resistance toward ribosome-targeting macrolide antibiotics has limited their clinical utility and urged the search for superior compounds. Macrolones are synthetic macrolide derivatives with a quinolone side chain, structurally similar to DNA topoisomerase-targeting fluoroquinolones. While macrolones show enhanced activity, their modes of action have remained unknown. Here, we present the first structures of ribosome-bound macrolones, showing that the macrolide part occupies the macrolide-binding site in the ribosomal exit tunnel, whereas the quinolone moiety establishes new interactions with the tunnel. Macrolones efficiently inhibit both the ribosome and DNA topoisomerase in vitro. However, in the cell, they target either the ribosome or DNA gyrase or concurrently both of them. In contrast to macrolide or fluoroquinolone antibiotics alone, dual-targeting macrolones are less prone to select resistant bacteria carrying target-site mutations or to activate inducible macrolide resistance genes. Furthermore, because some macrolones engage Erm-modified ribosomes, they retain activity even against strains with constitutive erm resistance genes. | 2024 | 39039256 |
| 777 | 4 | 0.9979 | Multiantibiotic resistance caused by active drug extrusion in Pseudomonas aeruginosa and other gram-negative bacteria. All living organisms have been exposed to noxious compounds throughout their long evolutionary history and those surviving have evolved to fabricate devices that detoxicate and extrude these life threatening substances. It is likely, therefore, that all viable organisms, from bacteria to mammals, are equipped with active extrusion machinery. When bacteria are attacked by antibiotics, they use these tactics to combat the drugs and to develop resistance. Drugs extrusion machinery in Gram-negative bacteria is complex, consisting of the inner membrane transporter which acts as an energy-dependent extrusion pump; a binding protein which presumably connect both membranes; and the outer membrane exit channel. The extrusion pump assemblies are often encoded by chromosomal genes and might be expressed by mutation(s) or induced in the presence of drug(s). | 1997 | 9353746 |
| 775 | 5 | 0.9979 | Time dependent asymptotic analysis of the gene regulatory network of the AcrAB-TolC efflux pump system in gram-negative bacteria. Efflux pumps are a mechanism of intrinsic and evolved resistance in bacteria. If an efflux pump can expel an antibiotic so that its concentration within the cell is below a killing threshold the bacteria are resistant to the antibiotic. Efflux pumps may be specific or they may pump various different substances. This is why many efflux pumps confer multi drug resistance (MDR). In particular over expression of the AcrAB-TolC efflux pump system confers MDR in both Salmonella and Escherichia coli. We consider the complex gene regulation network that controls expression of genes central to controlling the efflux associated genes acrAB and acrEF in Salmonella. We present the first mathematical model of this gene regulatory network in the form of a system of ordinary differential equations. Using a time dependent asymptotic analysis, we examine in detail the behaviour of the efflux system on various different timescales. Asymptotic approximations of the steady states provide an analytical comparison of targets for efflux inhibition. | 2021 | 33694073 |
| 764 | 6 | 0.9978 | Fungal ATP-binding cassette (ABC) transporters in drug resistance & detoxification. Pleiotropic drug resistance (PDR) is a well-described phenomenon occurring in fungi. PDR shares several similarities with processes in bacteria and higher eukaryotes. In mammalian cells, multidrug resistance (MDR) develops from an initial single drug resistance, eventually leading to a broad cross-resistance to many structurally and functionally unrelated compounds. Notably, a number of membrane-embedded energy-consuming ATP-binding cassette (ABC) transporters have been implicated in the development of PDR/MDR phenotypes. The yeast Saccharomyces cerevisiae genome harbors some 30 genes encoding ABC proteins, several of which mediate PDR. Therefore, yeast served as an important model organism to study the functions of evolutionary conserved ABC genes, including those mediating clinical antifungal resistance in fungal pathogens. Moreover, yeast cells lacking endogenous ABC pumps are hypersensitive to many antifungal drugs, making them suitable for functional studies and cloning of ABC transporters from fungal pathogens such as Candida albicans. This review discusses drug resistance phenomena mediated by ABC transporters in the model system S. cerevisiae and certain fungal pathogens. | 2006 | 16611035 |
| 776 | 7 | 0.9978 | Exploring functional interplay amongst Escherichia coli efflux pumps. Bacterial efflux pumps exhibit functional interplay that can translate to additive or multiplicative effects on resistance to antimicrobial compounds. In diderm bacteria, two different efflux pump structural types - single-component inner membrane efflux pumps and cell envelope-spanning multicomponent systems - cooperatively export antimicrobials with cytoplasmic targets from the cell. Harnessing our recently developed efflux platform, which is built upon an extensively efflux-deficient strain of Escherichia coli, here we explore interplay amongst a panel of diverse E. coli efflux pumps. Specifically, we assessed the effect of simultaneously expressing two efflux pump-encoding genes on drug resistance, including single-component inner membrane efflux pumps (MdfA, MdtK and EmrE), tripartite complexes (AcrAB, AcrAD, MdtEF and AcrEF), and the acquired TetA(C) tetracycline resistance pump. Overall, the expression of two efflux pump-encoding genes from the same structural type did not enhance resistance levels regardless of the antimicrobial compound or efflux pump under investigation. In contrast, a combination of the tripartite efflux systems with single-component pumps sharing common substrates provided multiplicative increases to antimicrobial resistance levels. In some instances, resistance was increased beyond the product of resistance provided by the two pumps individually. In summary, the developed efflux platform enables the isolation of efflux pump function, facilitating the identification of interactions between efflux pumps. | 2022 | 36318669 |
| 284 | 8 | 0.9978 | Expression of a transposable antibiotic resistance element in Saccharomyces. Some eukaryotic genes can be expressed in bacteria but there are few examples of the expression of prokaryotic genes in eukaryotes. Antibiotic G418 is a 2-deoxystreptamine antibiotic that is structurally related to gentamicin but has inhibitory activity against a much wider variety of pro- and eukaryotic organisms. In bacteria, resistance to G418 can be determined by several plasmid-encoded modifiying enzymes and, in view of the broad spectrum of activity of G418, we considered that this antibiotic might be useful as a selective agent for the introduction of these antibiotic resistance genes into a eukaryotic organism such as Saccharomyces cerevisiae. Additional impetus for these experiments came from the knowledge that certain of the G418-resistance determinants in bacteria are carried on transposable elements; a study of the properties of these elements in eukaryotes would be intriguing. | 1980 | 6253817 |
| 796 | 9 | 0.9978 | The internal gene duplication and interrupted coding sequences in the MmpL genes of Mycobacterium tuberculosis: Towards understanding the multidrug transport in an evolutionary perspective. The multidrug resistance has emerged as a major problem in the treatment of many of the infectious diseases. Tuberculosis (TB) is one of such disease caused by Mycobacterium tuberculosis. There is short term chemotherapy to treat the infection, but the main hurdle is the development of the resistance to antibiotics. This resistance is primarily due to the impermeable mycolic acid rich cell wall of the bacteria and other factors such as efflux of antibiotics from the bacterial cell. The MmpL (Mycobacterial Membrane Protein Large) proteins of mycobacteria are involved in the lipid transport and antibiotic efflux as indicated by the preliminary reports. We present here, comprehensive comparative sequence and structural analysis, which revealed topological signatures shared by the MmpL proteins and RND (Resistance Nodulation Division) multidrug efflux transporters. This provides evidence in support of the notion that they belong to the extended RND permeases superfamily. In silico modelled tertiary structures are in homology with an integral membrane component present in all of the RND efflux pumps. We document internal gene duplication and gene splitting events happened in the MmpL genes, which further elucidate the molecular functions of these putative transporters in an evolutionary perspective. | 2015 | 25841626 |
| 8215 | 10 | 0.9978 | Insight into Two ABC Transporter Families Involved in Lantibiotic Resistance. Antimicrobial peptides, which contain (methyl)-lanthionine-rings are called lantibiotics. They are produced by several Gram-positive bacteria and are mainly active against these bacteria. Although these are highly potent antimicrobials, some human pathogenic bacteria express specific ABC transporters that confer resistance and counteract their antimicrobial activity. Two distinct ABC transporter families are known to be involved in this process. These are the Cpr- and Bce-type ABC transporter families, named after their involvement in cationic peptide resistance in Clostridium difficile, and bacitracin efflux in Bacillus subtilis, respectively. Both resistance systems differentiate to each other in terms of the proteins involved. Here, we summarize the current knowledge and describe the divergence as well as the common features present in both the systems to confer lantibiotic resistance. | 2017 | 29404338 |
| 786 | 11 | 0.9978 | The Varied Role of Efflux Pumps of the MFS Family in the Interplay of Bacteria with Animal and Plant Cells. Efflux pumps represent an important and large group of transporter proteins found in all organisms. The importance of efflux pumps resides in their ability to extrude a wide range of antibiotics, resulting in the emergence of multidrug resistance in many bacteria. Besides antibiotics, multidrug efflux pumps can also extrude a large variety of compounds: Bacterial metabolites, plant-produced compounds, quorum-sensing molecules, and virulence factors. This versatility makes efflux pumps relevant players in interactions not only with other bacteria, but also with plant or animal cells. The multidrug efflux pumps belonging to the major facilitator superfamily (MFS) are widely distributed in microbial genomes and exhibit a large spectrum of substrate specificities. Multidrug MFS efflux pumps are present either as single-component transporters or as tripartite complexes. In this review, we will summarize how the multidrug MFS efflux pumps contribute to the interplay between bacteria and targeted host cells, with emphasis on their role in bacterial virulence, in the colonization of plant and animal host cells and in biofilm formation. We will also address the complexity of these interactions in the light of the underlying regulatory networks required for the effective activation of efflux pump genes. | 2019 | 31443538 |
| 4444 | 12 | 0.9977 | Mechanisms of resistance to fluoroquinolones. Fluoroquinolones have some of the properties of an 'ideal' anti-microbial agent. Because of their potent broad spectrum activity and absence of transferable mechanism of resistance or inactivating enzymes, it was hoped that clinical resistance to this useful group of drugs would not occur. However, over the years, due to intense selective pressure and relative lack of potency of the available quinolones against some strains, bacteria have evolved at least two mechanisms of resistance: (i) alteration of molecular targets, and (ii) reduction of drug accumulation. DNA gyrase and topoisomerase IV are the two molecular targets of fluoroquinolones. Mutations in specified regions (quinolone resistance-determining region) in genes coding for the gyrase and/or topoisomerase leads to clinical resistance. An efflux pump effective in pumping out hydrophilic quinolones has been described. Newer fluoroquinolones which recognize both molecular targets and have improved pharmacokinetic properties offer hope of higher potency, thereby reducing the probability of development of resistance. | 1999 | 10573971 |
| 792 | 13 | 0.9977 | Multiple antibiotic resistance and efflux. Multiple antibiotic resistance in bacteria was at first thought to be caused exclusively by the combination of several resistance genes, each coding for resistance to a single drug. More recently, it became clear that such phenotypes are often achieved by the activity of drug efflux pumps. Some of these efflux pumps exhibit an extremely wide specificity covering practically all antibiotics, chemotherapeutic agents, detergents, dyes, and other inhibitors, the exception perhaps being very hydrophilic compounds. Such efflux pumps work with exceptional efficiency in Gram-negative bacteria through their synergistic interaction with the outer membrane barrier. It is disturbing that the antibacterial agents of the most advanced type, which are unaffected by common resistance mechanisms, are precisely the compounds whose use appears to select for multidrug-resistant mutants that overproduce these efflux pumps of wide specificity. | 1998 | 10066525 |
| 787 | 14 | 0.9977 | Multidrug-resistance efflux pumps - not just for resistance. It is well established that multidrug-resistance efflux pumps encoded by bacteria can confer clinically relevant resistance to antibiotics. It is now understood that these efflux pumps also have a physiological role(s). They can confer resistance to natural substances produced by the host, including bile, hormones and host-defence molecules. In addition, some efflux pumps of the resistance nodulation division (RND) family have been shown to have a role in the colonization and the persistence of bacteria in the host. Here, I present the accumulating evidence that multidrug-resistance efflux pumps have roles in bacterial pathogenicity and propose that these pumps therefore have greater clinical relevance than is usually attributed to them. | 2006 | 16845433 |
| 795 | 15 | 0.9977 | Multidrug resistance in Gram-negative bacteria. Broadly specific, so-called multidrug, efflux mechanisms are now known to contribute significantly to intrinsic and acquired multidrug resistance in a number of Gram-negative bacteria, and the boom in bacterial genomics has confirmed the distribution of these systems in all bacteria. This broad distribution of multidrug transporters lends a certain credibility to suggestions that they play a housekeeping role in the cell, beyond any contributions they may make to antimicrobial efflux and resistance. In many instances, these transporters are dispensable, arguing against their carrying out essential cellular functions; nevertheless, the multiplicity of these broadly specific export systems within a given microorganism, often with overlapping substrate specificity, may explain the dispensability of individual exporters. Whatever their intended function, however, their conservation in so many organisms highlights their probable general importance in antimicrobial resistance, particularly in Gram-negative bacteria whose outer membranes work synergistically with many of these export systems to promote drug exclusion. | 2001 | 11587924 |
| 789 | 16 | 0.9977 | Antibiotic efflux mechanisms. Bacterial genomes sequenced to date almost invariably contain genes apparently coding for multidrug efflux pumps, and the yeast genome contains more than 30 putative multidrug efflux genes. Thus it is not surprising that multidrug efflux is a major cause of intrinsic drug resistance in many microorganisms, and plays an even more prominent role in organisms with a low-permeability cell wall, such as Gram negative bacteria in general and Pseudomonas aeruginosa in particular, as well as Mycobacterium species. Furthermore, overproduction of intrinsic pumps, or acquisition of pump genes from external sources, often results in high levels of resistance. This review discusses the classification of efflux proteins, their mechanism of action, the regulation of their expression, and the clinical significance of efflux pumps. | 1999 | 17035817 |
| 4426 | 17 | 0.9977 | Microbial multidrug resistance. Multiresistance plasmids and transposons, the integrons, the co-amplification of several resistance genes or finally the accumulation of independent mutations can lead to microorganisms resistant to multiple drugs. On the other hand multidrug resistance is due to an efflux pump conferring resistance to unrelated drugs. These microbial efflux pumps are belonging to various transporter families and are often encoded in microbial genomes. There is mounting evidence that these efflux systems are responsible for clinical multidrug resistance in bacteria, yeasts and parasites. | 1997 | 18611799 |
| 765 | 18 | 0.9977 | Yeast ATP-binding cassette transporters: cellular cleaning pumps. Numerous ATP-binding cassette (ABC) proteins have been implicated in multidrug resistance, and some are also intimately connected to genetic diseases. For example, mammalian ABC proteins such as P-glycoproteins or multidrug resistance-associated proteins are associated with multidrug resistance phenomena (MDR), thus hampering anticancer therapy. Likewise, homologues in bacteria, fungi, or parasites are tightly associated with multidrug and antibiotic resistance. Several orthologues of mammalian MDR genes operate in the unicellular eukaryote Saccharomyces cerevisiae. Their functions have been linked to stress response, cellular detoxification, and drug resistance. This chapter discusses those yeast ABC transporters implicated in pleiotropic drug resistance and cellular detoxification. We describe strategies for their overexpression, biochemical purification, functional analysis, and a reconstitution in phospholipid vesicles, all of which are instrumental to better understanding their mechanisms of action and perhaps their physiological function. | 2005 | 16399365 |
| 788 | 19 | 0.9977 | Clinically relevant chromosomally encoded multidrug resistance efflux pumps in bacteria. Efflux pump genes and proteins are present in both antibiotic-susceptible and antibiotic-resistant bacteria. Pumps may be specific for one substrate or may transport a range of structurally dissimilar compounds (including antibiotics of multiple classes); such pumps can be associated with multiple drug (antibiotic) resistance (MDR). However, the clinical relevance of efflux-mediated resistance is species, drug, and infection dependent. This review focuses on chromosomally encoded pumps in bacteria that cause infections in humans. Recent structural data provide valuable insights into the mechanisms of drug transport. MDR efflux pumps contribute to antibiotic resistance in bacteria in several ways: (i) inherent resistance to an entire class of agents, (ii) inherent resistance to specific agents, and (iii) resistance conferred by overexpression of an efflux pump. Enhanced efflux can be mediated by mutations in (i) the local repressor gene, (ii) a global regulatory gene, (iii) the promoter region of the transporter gene, or (iv) insertion elements upstream of the transporter gene. Some data suggest that resistance nodulation division systems are important in pathogenicity and/or survival in a particular ecological niche. Inhibitors of various efflux pump systems have been described; typically these are plant alkaloids, but as yet no product has been marketed. | 2006 | 16614254 |