# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 4429 | 0 | 1.0000 | General mechanisms of resistance to antibiotics. Resistance to antimicrobial agents may result from intrinsic properties of organisms, through mutation and through plasmid- and transposon-specified genes. beta-Lactam resistance is most frequently associated with one or more chromosomal- or plasmid-specified beta-lactamases. Recently, mutations modifying penicillin-binding proteins have been detected with increased frequency as a cause of beta-lactam resistance. Mixed mechanisms, reduced permeability and tolerance are other causes of resistance. Aminoglycoside resistance always involves some modification of drug uptake, most often due to a variety of enzymes modifying these compounds. Reduced uptake is a primary cause of resistance in anaerobic bacteria and bacteria growing anaerobically, some strains of Pseudomonas aeruginosa, and mutants that arise during antimicrobial therapy and are defective in energy-generation systems. Resistance to other antimicrobial agents is presented in tabular form. | 1988 | 3062000 |
| 4428 | 1 | 0.9999 | Multidrug resistance in enteric and other gram-negative bacteria. In Gram-negative bacteria, multidrug resistance is a term that is used to describe mechanisms of resistance by chromosomal genes that are activated by induction or mutation caused by the stress of exposure to antibiotics in natural and clinical environments. Unlike plasmid-borne resistance genes, there is no alteration or degradation of drugs or need for genetic transfer. Exposure to a single drug leads to cross-resistance to many other structurally and functionally unrelated drugs. The only mechanism identified for multidrug resistance in bacteria is drug efflux by membrane transporters, even though many of these transporters remain to be identified. The enteric bacteria exhibit mostly complex multidrug resistance systems which are often regulated by operons or regulons. The purpose of this review is to survey molecular mechanisms of multidrug resistance in enteric and other Gram-negative bacteria, and to speculate on the origins and natural physiological functions of the genes involved. | 1996 | 8647368 |
| 4832 | 2 | 0.9999 | Antibiotic resistance of Pseudomonas species. Pseudomonas species are highly versatile organisms with genetic and physiologic capabilities that allow them to flourish in environments hostile to most pathogenic bacteria. Within the lung of the patient with cystic fibrosis, exposed to a number of antimicrobial agents, highly resistant clones of Pseudomonas are selected. These may have acquired plasmid-mediated genes encoding a variety of beta-lactamases or aminoglycoside modifying enzymes. Frequently these resistance determinants are on transposable elements, facilitating their dissemination among the population of bacteria. Mutations in chromosomal genes can also occur, resulting in constitutive expression of normally repressed enzymes, such as the chromosomal cephalosporinase of Pseudomonas aeruginosa or Pseudomonas cepacia. These enzymes may confer resistance to the expanded-spectrum beta-lactam drugs. Decreased cellular permeability to the beta-lactams and the aminoglycosides also results in clinically significant antibiotic resistance. The development of new drugs with anti-Pseudomonas activity, beta-lactam agents and the quinolones, has improved the potential for effective chemotherapy but has not surpassed the potential of the organisms to develop resistance. | 1986 | 3701534 |
| 4830 | 3 | 0.9999 | Mechanisms of resistance to quinolones. The increased use of fluoroquinolones has led to increasing resistance to these antimicrobials, with rates of resistance that vary by both organism and geographic region. Resistance to fluoroquinolones typically arises as a result of alterations in the target enzymes (DNA gyrase and topoisomerase IV) and of changes in drug entry and efflux. Mutations are selected first in the more susceptible target: DNA gyrase, in gram-negative bacteria, or topoisomerase IV, in gram-positive bacteria. Additional mutations in the next most susceptible target, as well as in genes controlling drug accumulation, augment resistance further, so that the most-resistant isolates have mutations in several genes. Resistance to quinolones can also be mediated by plasmids that produce the Qnr protein, which protects the quinolone targets from inhibition. Qnr plasmids have been found in the United States, Europe, and East Asia. Although Qnr by itself produces only low-level resistance, its presence facilitates the selection of higher-level resistance mutations, thus contributing to the alarming increase in resistance to quinolones. | 2005 | 15942878 |
| 4441 | 4 | 0.9999 | Mechanisms of antimicrobial resistance in bacteria. The treatment of bacterial infections is increasingly complicated by the ability of bacteria to develop resistance to antimicrobial agents. Antimicrobial agents are often categorized according to their principal mechanism of action. Mechanisms include interference with cell wall synthesis (e.g., beta-lactams and glycopeptide agents), inhibition of protein synthesis (macrolides and tetracyclines), interference with nucleic acid synthesis (fluoroquinolones and rifampin), inhibition of a metabolic pathway (trimethoprim-sulfamethoxazole), and disruption of bacterial membrane structure (polymyxins and daptomycin). Bacteria may be intrinsically resistant to > or =1 class of antimicrobial agents, or may acquire resistance by de novo mutation or via the acquisition of resistance genes from other organisms. Acquired resistance genes may enable a bacterium to produce enzymes that destroy the antibacterial drug, to express efflux systems that prevent the drug from reaching its intracellular target, to modify the drug's target site, or to produce an alternative metabolic pathway that bypasses the action of the drug. Acquisition of new genetic material by antimicrobial-susceptible bacteria from resistant strains of bacteria may occur through conjugation, transformation, or transduction, with transposons often facilitating the incorporation of the multiple resistance genes into the host's genome or plasmids. Use of antibacterial agents creates selective pressure for the emergence of resistant strains. Herein 3 case histories-one involving Escherichia coli resistance to third-generation cephalosporins, another focusing on the emergence of vancomycin-resistant Staphylococcus aureus, and a third detailing multidrug resistance in Pseudomonas aeruginosa--are reviewed to illustrate the varied ways in which resistant bacteria develop. | 2006 | 16735149 |
| 4833 | 5 | 0.9999 | Emerging mechanisms of fluoroquinolone resistance. Broad use of fluoroquinolones has been followed by emergence of resistance, which has been due mainly to chromosomal mutations in genes encoding the subunits of the drugs' target enzymes, DNA gyrase and topoisomerase IV, and in genes that affect the expression of diffusion channels in the outer membrane and multidrug-resistance efflux systems. Resistance emerged first in species in which single mutations were sufficient to cause clinically important levels of resistance (e.g., Staphylococcus aureus and Pseudomonas aeruginosa). Subsequently, however, resistance has emerged in bacteria such as Campylobacter jejuni, Escherichia coli, and Neisseria gonorrhoeae, in which multiple mutations are required to generate clinically important resistance. In these circumstances, the additional epidemiologic factors of drug use in animals and human-to-human spread appear to have contributed. Resistance in Streptococcus pneumoniae, which is currently low, will require close monitoring as fluoroquinolones are used more extensively for treating respiratory tract infections. | 2001 | 11294736 |
| 4442 | 6 | 0.9999 | Mechanisms of antimicrobial resistance in bacteria. The treatment of bacterial infections is increasingly complicated by the ability of bacteria to develop resistance to antimicrobial agents. Antimicrobial agents are often categorized according to their principal mechanism of action. Mechanisms include interference with cell wall synthesis (eg, beta-lactams and glycopeptide agents), inhibition of protein synthesis (macrolides and tetracyclines), interference with nucleic acid synthesis (fluoroquinolones and rifampin), inhibition of a metabolic pathway (trimethoprim-sulfamethoxazole), and disruption of bacterial membrane structure (polymyxins and daptomycin). Bacteria may be intrinsically resistant to > or =1 class of antimicrobial agents, or may acquire resistance by de novo mutation or via the acquisition of resistance genes from other organisms. Acquired resistance genes may enable a bacterium to produce enzymes that destroy the antibacterial drug, to express efflux systems that prevent the drug from reaching its intracellular target, to modify the drug's target site, or to produce an alternative metabolic pathway that bypasses the action of the drug. Acquisition of new genetic material by antimicrobial-susceptible bacteria from resistant strains of bacteria may occur through conjugation, transformation, or transduction, with transposons often facilitating the incorporation of the multiple resistance genes into the host's genome or plasmids. Use of antibacterial agents creates selective pressure for the emergence of resistant strains. Herein 3 case histories-one involving Escherichia coli resistance to third-generation cephalosporins, another focusing on the emergence of vancomycin-resistant Staphylococcus aureus, and a third detailing multidrug resistance in Pseudomonas aeruginosa-are reviewed to illustrate the varied ways in which resistant bacteria develop. | 2006 | 16813980 |
| 4835 | 7 | 0.9999 | Genetic and biochemical basis of resistance of Enterobacteriaceae to beta-lactam antibiotics. Resistance to beta-lactam drugs is usually determined by genes mediating the production of beta-lactamases. These genes can be located on resistance plasmids or on the chromosome. Resistance to drugs which have been available for many years is mostly transposable. Although the origin of these genes is not known, it is possible to draw a hypothetical flow diagram of the evolution of resistance genes in general. The mechanism of resistance although mediated in Gram-negative bacteria mostly by beta-lactamases cannot be simply described as the hydrolytic function of the enzyme. It is a complex interaction involving the affinity of the drug for the target and the lactamase, the amount of drug in the periplasmic space, the amount of enzyme and the number of lethal target sites. Usually one of these factors is predominant. | 1986 | 3491818 |
| 4831 | 8 | 0.9999 | Mechanism of quinolone resistance in anaerobic bacteria. Several recently developed quinolones have excellent activity against a broad range of aerobic and anaerobic bacteria and are thus potential drugs for the treatment of serious anaerobic and mixed infections. Resistance to quinolones is increasing worldwide, but is still relatively infrequent among anaerobes. Two main mechanisms, alteration of target enzymes (gyrase and topoisomerase IV) caused by chromosomal mutations in encoding genes, or reduced intracellular accumulation due to increased efflux of the drug, are associated with quinolone resistance. These mechanisms have also been found in anaerobic species. High-level resistance to the newer broad-spectrum quinolones often requires stepwise mutations in target genes. The increasing emergence of resistance among anaerobes may be a consequence of previous widespread use of quinolones, which may have enriched first-step mutants in the intestinal tract. Quinolone resistance in the Bacteroides fragilis group strains is strongly correlated with amino acid substitutions at positions 82 and 86 in GyrA (equivalent to positions 83 and 87 of Escherichia coli). Several studies have indicated that B. fragilis group strains possess efflux pump systems that actively expel quinolones, leading to resistance. DNA gyrase seems also to be the primary target for quinolones in Clostridium difficile, since amino acid substitutions in GyrA and GyrB have been detected in resistant strains. To what extent other mechanisms, such as mutational events in other target genes or alterations in outer-membrane proteins, contribute to resistance among anaerobes needs to be further investigated. | 2003 | 12848726 |
| 4402 | 9 | 0.9999 | Mechanisms of antimicrobial resistance in Stenotrophomonas maltophilia: a review of current knowledge. Introduction: Stenotrophomonas maltophilia is a prototype of bacteria intrinsically resistant to antibiotics. The reduced susceptibility of this microorganism to antimicrobials mainly relies on the presence in its chromosome of genes encoding efflux pumps and antibiotic inactivating enzymes. Consequently, the therapeutic options for treating S. maltophilia infections are limited.Areas covered: Known mechanisms of intrinsic, acquired and phenotypic resistance to antibiotics of S. maltophilia and the consequences of such resistance for treating S. maltophilia infections are discussed. Acquisition of some genes, mainly those involved in co-trimoxazole resistance, contributes to acquired resistance. Mutation, mainly in the regulators of chromosomally-encoded antibiotic resistance genes, is a major cause for S. maltophilia acquisition of resistance. The expression of some of these genes is triggered by specific signals or stressors, which can lead to transient phenotypic resistance.Expert opinion: Treatment of S. maltophilia infections is difficult because this organism presents low susceptibility to antibiotics. Besides, it can acquire resistance to antimicrobials currently in use. Particularly problematic is the selection of mutants overexpressing efflux pumps since they present a multidrug resistance phenotype. The use of novel antimicrobials alone or in combination, together with the development of efflux pumps' inhibitors may help in fighting S. maltophilia infections. | 2020 | 32052662 |
| 4427 | 10 | 0.9999 | Mechanisms of quinolone action and microbial response. Over the years, chromosomal mapping of the bacterial genome of Escherichia coli has demonstrated that many loci are associated with quinolone resistance, which is mainly a result of chromosomal mutation or alteration of the quantity or type of porins in the outer membrane of Gram-negative bacteria. There has been one report of a small and confined episode of plasmid-mediated resistance to fluoroquinolones, which did not appear to persist. With the increasingly widespread use of an expanding range of fluoroquinolone antibiotics, a range and mix in individual bacterial isolates of the different mechanisms of resistance to fluoroquinolones will undoubtedly be encountered amongst clinically significant bacteria. Currently, transferable resistance is extremely rare and most resistant bacteria arise from clonal expansion of mutated strains. However, it is conceivable that in the future, horizontal gene transfer may become a more important means of conferring resistance to fluoroquinolones. | 2003 | 12702701 |
| 4443 | 11 | 0.9999 | Cellular Studies of an Aminoglycoside Potentiator Reveal a New Inhibitor of Aminoglycoside Resistance. Aminoglycosides are a group of broad-spectrum antibiotics that have been used in the clinic for almost a century. The rapid spread of bacterial genes coding for aminoglycoside-modifying enzymes has, however, dramatically decreased the utility of aminoglycosides. We have previously reported several aminoglycoside potentiators that work by inhibiting aminoglycoside N-6'-acetyltransferase, one of the most common determinants of aminoglycoside resistance. Among these, prodrugs that combine the structure of an aminoglycoside with that of pantothenate into one molecule are especially promising. We report here a series of cellular studies to investigate the activity and mechanism of action of these prodrugs further. Our results reveal a new aminoglycoside resistance inhibitor, as well as the possibility that these prodrugs are transformed into more than one inhibitor in bacteria. We also report that the onset of the potentiators is rapid. Their low cell cytotoxicity, good stability, and potentiation of various aminoglycosides, against both Gram-positive and Gram-negative bacteria, make them interesting compounds for the development of new drugs. | 2018 | 30059603 |
| 4440 | 12 | 0.9999 | Antibiotic resistance mechanisms of clinically important bacteria. Bacterial resistance to antimicrobial drugs is an increasing health and economic problem. Bacteria may be innate resistant or acquire resistance to one or few classes of antimicrobial agents. Acquired resistance arises from: (i) mutations in cell genes (chromosomal mutation) leading to cross-resistance, (ii) gene transfer from one microorganism to other by plasmids (conjugation or transformation), transposons (conjugation), integrons and bacteriophages (transduction). After a bacterium gains resistance genes to protect itself from various antimicrobial agents, bacteria can use several biochemical types of resistance mechanisms: antibiotic inactivation (interference with cell wall synthesis, e.g., β-lactams and glycopeptide), target modification (inhibition of protein synthesis, e.g., macrolides and tetracyclines; interference with nucleic acid synthesis, e.g., fluoroquinolones and rifampin), altered permeability (changes in outer membrane, e.g., aminoglycosides; new membrane transporters, e.g., chloramphenicol), and "bypass" metabolic pathway (inhibition of metabolic pathway, e.g., trimethoprim-sulfamethoxazole). | 2011 | 21822035 |
| 4444 | 13 | 0.9999 | 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 |
| 9926 | 14 | 0.9999 | beta-Lactamases of gram-negative bacteria: new challenges for new drugs. The major emphasis in new drug design within the beta-lactam family has been on compounds less susceptible to hydrolysis by beta-lactamases and on combinations containing an enzyme-labile drug plus a beta-lactamase inhibitor. The introduction of such new compounds into clinical use has been followed by the discovery of novel mechanisms of resistance among gram-negative bacteria. These include the appearance of new enzymes, many of which are derivatives of older beta-lactamases. In addition, genes for certain broad-spectrum enzymes previously restricted to chromosomal sites have moved onto plasmids. There is now a greater appreciation of how alterations in enzyme expression--either alone or in concert with changes in drug permeation--can also lead to resistance. Clearly, recent events in the development of new beta-lactam agents have led to a new phase in the understanding of beta-lactam resistance. | 1992 | 1600011 |
| 4829 | 15 | 0.9999 | Diversity of the mechanisms of resistance to beta-lactam antibiotics. The sensitivity of a bacterium to beta-lactam antibiotics depends upon the interplay between 3 independent factors: the sensitivity of the essential penicillin-binding enzyme(s), the quantity and properties of the beta-lactamase(s) and the diffusion barrier that the outer-membrane of Gram-negative bacteria can represent. Those three factors can be modified by mutations or by the horizontal transfer of genes or portions of genes. | 1991 | 1961980 |
| 6275 | 16 | 0.9999 | Resistance to fosfomycin: Mechanisms, Frequency and Clinical Consequences. Fosfomycin has been used for the treatment of infections due to susceptible and multidrug-resistant (MDR) bacteria. It inhibits bacterial cell wall synthesis through a unique mechanism of action at a step prior to that inhibited by β-lactams. Fosfomycin enters the bacterium through membrane channels/transporters and inhibits MurA, which initiates peptidoglycan (PG) biosynthesis of the bacterial cell wall. Several bacteria display inherent resistance to fosfomycin mainly through MurA mutations. Acquired resistance involves, in order of decreasing frequency, modifications of membrane transporters that prevent fosfomycin from entering the bacterial cell, acquisition of plasmid-encoded genes that inactivate fosfomycin, and MurA mutations. Fosfomycin resistance develops readily in vitro but less so in vivo. Mutation frequency is higher among Pseudomonas aeruginosa and Klebsiella spp. compared with Escherichia coli and is associated with fosfomycin concentration. Mutations in cAMP regulators, fosfomycin transporters and MurA seem to be associated with higher biological cost in Enterobacteriaceae but not in Pseudomonas spp. The contribution of fosfomycin inactivating enzymes in emergence and spread of fosfomycin resistance currently seems low-to-moderate, but their presence in transferable plasmids may potentially provide the best means for the spread of fosfomycin resistance in the future. Their co-existence with genes conferring resistance to other antibiotic classes may increase the emergence of MDR strains. Although susceptibility rates vary, rates seem to increase in settings with higher fosfomycin use and among multidrug-resistant pathogens. | 2019 | 30268576 |
| 4834 | 17 | 0.9999 | A retrospective view of beta-lactamases. The discovery of a penicillinase (later shown be a beta-lactamase) 50 years ago in Oxford came from the thought that the resistance of many Gram-negative bacteria to Fleming's penicillinase might be due to their production of a penicillin-destroying enzyme. The emergence of penicillinase-producing staphylococci in the early 1950s, particularly in hospitals, raised the question whether the medical value of penicillin would decline. The introduction of new semi-synthetic penicillins and cephalosporins in the 1960s began to reveal many beta-lactamases distinguishable by their different substrate profiles. In this period it was established that genes encoding beta-lactamases from Gram-negative bacilli could be carried from one organism to another on plasmids and also that penicillin inhibited a transpeptidase involved in bacterial cell wall synthesis. During the last two decades a number of these enzymes have been purified and the genes encoding them have been cloned. Much has now been learned, with the aid of powerful modern techniques, about their structures, their active sites, their relationship to penicillin-sensitive proteins in bacteria and to their likely evolution. Further knowledge may contribute to a more rational approach to chemotherapy in this area. Experience suggests that a need for new substances will continue. | 1991 | 1875234 |
| 4252 | 18 | 0.9999 | Extreme antimicrobial peptide and polymyxin B resistance in the genus Burkholderia. Cationic antimicrobial peptides and polymyxins are a group of naturally occurring antibiotics that can also possess immunomodulatory activities. They are considered a new source of antibiotics for treating infections by bacteria that are resistant to conventional antibiotics. Members of the genus Burkholderia, which includes various human pathogens, are inherently resistant to antimicrobial peptides. The resistance is several orders of magnitude higher than that of other Gram-negative bacteria such as Escherichia coli, Salmonella enterica, or Pseudomonas aeruginosa. This review summarizes our current understanding of antimicrobial peptide and polymyxin B resistance in the genus Burkholderia. These bacteria possess major and minor resistance mechanisms that will be described in detail. Recent studies have revealed that many other emerging Gram-negative opportunistic pathogens may also be inherently resistant to antimicrobial peptides and polymyxins and we propose that Burkholderia sp. are a model system to investigate the molecular basis of the resistance in extremely resistant bacteria. Understanding resistance in these types of bacteria will be important if antimicrobial peptides come to be used regularly for the treatment of infections by susceptible bacteria because this may lead to increased resistance in the species that are currently susceptible and may also open up new niches for opportunistic pathogens with high inherent resistance. | 2011 | 22919572 |
| 4251 | 19 | 0.9999 | Extreme antimicrobial Peptide and polymyxin B resistance in the genus burkholderia. Cationic antimicrobial peptides and polymyxins are a group of naturally occurring antibiotics that can also possess immunomodulatory activities. They are considered a new source of antibiotics for treating infections by bacteria that are resistant to conventional antibiotics. Members of the genus Burkholderia, which includes various human pathogens, are inherently resistant to antimicrobial peptides. The resistance is several orders of magnitude higher than that of other Gram-negative bacteria such as Escherichia coli, Salmonella enterica, or Pseudomonas aeruginosa. This review summarizes our current understanding of antimicrobial peptide and polymyxin B resistance in the genus Burkholderia. These bacteria possess major and minor resistance mechanisms that will be described in detail. Recent studies have revealed that many other emerging Gram-negative opportunistic pathogens may also be inherently resistant to antimicrobial peptides and polymyxins and we propose that Burkholderia sp. are a model system to investigate the molecular basis of the resistance in extremely resistant bacteria. Understanding resistance in these types of bacteria will be important if antimicrobial peptides come to be used regularly for the treatment of infections by susceptible bacteria because this may lead to increased resistance in the species that are currently susceptible and may also open up new niches for opportunistic pathogens with high inherent resistance. | 2011 | 21811491 |