# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 9774 | 0 | 1.0000 | A naturally inspired antibiotic to target multidrug-resistant pathogens. Gram-negative bacteria are responsible for an increasing number of deaths caused by antibiotic-resistant infections(1,2). The bacterial natural product colistin is considered the last line of defence against a number of Gram-negative pathogens. The recent global spread of the plasmid-borne mobilized colistin-resistance gene mcr-1 (phosphoethanolamine transferase) threatens the usefulness of colistin(3). Bacteria-derived antibiotics often appear in nature as collections of similar structures that are encoded by evolutionarily related biosynthetic gene clusters. This structural diversity is, at least in part, expected to be a response to the development of natural resistance, which often mechanistically mimics clinical resistance. Here we propose that a solution to mcr-1-mediated resistance might have evolved among naturally occurring colistin congeners. Bioinformatic analysis of sequenced bacterial genomes identified a biosynthetic gene cluster that was predicted to encode a structurally divergent colistin congener. Chemical synthesis of this structure produced macolacin, which is active against Gram-negative pathogens expressing mcr-1 and intrinsically resistant pathogens with chromosomally encoded phosphoethanolamine transferase genes. These Gram-negative bacteria include extensively drug-resistant Acinetobacter baumannii and intrinsically colistin-resistant Neisseria gonorrhoeae, which, owing to a lack of effective treatment options, are considered among the highest level threat pathogens(4). In a mouse neutropenic infection model, a biphenyl analogue of macolacin proved to be effective against extensively drug-resistant A. baumannii with colistin-resistance, thus providing a naturally inspired and easily produced therapeutic lead for overcoming colistin-resistant pathogens. | 2022 | 34987225 |
| 4253 | 1 | 0.9999 | Molecular mechanisms of polymyxin resistance and detection of mcr genes. Antibiotic resistance is an ever-increasing global problem. Major commercial antibiotics often fail to fight common bacteria, and some pathogens have become multi-resistant. Polymyxins are potent bactericidal antibiotics against gram-negative bacteria. Known resistance to polymyxin includes intrinsic, mutational and adaptive mechanisms, with the recently described horizontally acquired resistance mechanisms. In this review, we present several strategies for bacteria to develop enhanced resistance to polymyxins, focusing on changes in the outer membrane, efflux and other resistance determinants. Better understanding of the genes involved in polymyxin resistance may pave the way for the development of new and effective antimicrobial agents. We also report novel in silico tested primers for PCR assay that may be able distinguish colistin-resistant isolates carrying the plasmid-encoded mcr genes and will assist in combating the spread of colistin resistance in bacteria. | 2019 | 30439931 |
| 9776 | 2 | 0.9998 | Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria. Polymyxins are polycationic antimicrobial peptides that are currently the last-resort antibiotics for the treatment of multidrug-resistant, Gram-negative bacterial infections. The reintroduction of polymyxins for antimicrobial therapy has been followed by an increase in reports of resistance among Gram-negative bacteria. Some bacteria, such as Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii, develop resistance to polymyxins in a process referred to as acquired resistance, whereas other bacteria, such as Proteus spp., Serratia spp., and Burkholderia spp., are naturally resistant to these drugs. Reports of polymyxin resistance in clinical isolates have recently increased, including acquired and intrinsically resistant pathogens. This increase is considered a serious issue, prompting concern due to the low number of currently available effective antibiotics. This review summarizes current knowledge concerning the different strategies bacteria employ to resist the activities of polymyxins. Gram-negative bacteria employ several strategies to protect themselves from polymyxin antibiotics (polymyxin B and colistin), including a variety of lipopolysaccharide (LPS) modifications, such as modifications of lipid A with phosphoethanolamine and 4-amino-4-deoxy-L-arabinose, in addition to the use of efflux pumps, the formation of capsules and overexpression of the outer membrane protein OprH, which are all effectively regulated at the molecular level. The increased understanding of these mechanisms is extremely vital and timely to facilitate studies of antimicrobial peptides and find new potential drugs targeting clinically relevant Gram-negative bacteria. | 2014 | 25505462 |
| 9775 | 3 | 0.9998 | Current Update on Intrinsic and Acquired Colistin Resistance Mechanisms in Bacteria. Colistin regained global interest as a consequence of the rising prevalence of multidrug-resistant Gram-negative Enterobacteriaceae. In parallel, colistin-resistant bacteria emerged in response to the unregulated use of this antibiotic. However, some Gram-negative species are intrinsically resistant to colistin activity, such as Neisseria meningitides, Burkholderia species, and Proteus mirabilis. Most identified colistin resistance usually involves modulation of lipid A that decreases or removes early charge-based interaction with colistin through up-regulation of multistep capsular polysaccharide expression. The membrane modifications occur by the addition of cationic phosphoethanolamine (pEtN) or 4-amino-l-arabinose on lipid A that results in decrease in the negative charge on the bacterial surface. Therefore, electrostatic interaction between polycationic colistin and lipopolysaccharide (LPS) is halted. It has been reported that these modifications on the bacterial surface occur due to overexpression of chromosomally mediated two-component system genes (PmrAB and PhoPQ) and mutation in lipid A biosynthesis genes that result in loss of the ability to produce lipid A and consequently LPS chain, thereafter recently identified variants of plasmid-borne genes (mcr-1 to mcr-10). It was hypothesized that mcr genes derived from intrinsically resistant environmental bacteria that carried chromosomal pmrC gene, a part of the pmrCAB operon, code three proteins viz. pEtN response regulator PmrA, sensor kinase protein PmrAB, and phosphotransferase PmrC. These plasmid-borne mcr genes become a serious concern as they assist in the dissemination of colistin resistance to other pathogenic bacteria. This review presents the progress of multiple strategies of colistin resistance mechanisms in bacteria, mainly focusing on surface changes of the outer membrane LPS structure and other resistance genetic determinants. New handier and versatile methods have been discussed for rapid detection of colistin resistance determinants and the latest approaches to revert colistin resistance that include the use of new drugs, drug combinations and inhibitors. Indeed, more investigations are required to identify the exact role of different colistin resistance determinants that will aid in developing new less toxic and potent drugs to treat bacterial infections. Therefore, colistin resistance should be considered a severe medical issue requiring multisectoral research with proper surveillance and suitable monitoring systems to report the dissemination rate of these resistant genes. | 2021 | 34476235 |
| 4832 | 4 | 0.9998 | 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 |
| 4864 | 5 | 0.9998 | Colistin resistance mechanisms in Gram-negative bacteria: a Focus on Escherichia coli. Multidrug-resistant (MDR) Escherichia coli strains have rapidly increased worldwide, and effective antibiotic therapeutic options are becoming more restricted. As a polymyxin antibiotic, colistin has a long history of usage, and it is used as a final line of treatment for severe infections by Gram-negative bacteria (GNB) with high-level resistance. However, its application has been challenged by the emergence of E. coli colistin resistance. Hence, determining the mechanism that confers colistin resistance is crucial for monitoring and controlling the dissemination of colistin-resistant E. coli strains. This comprehensive review summarizes colistin resistance mechanisms in E. coli strains and concentrates on the history, mode of action, and therapeutic implications of colistin. We have mainly focused on the fundamental mechanisms of colistin resistance that are mediated by chromosomal or plasmid elements and discussed major mutations in the two-component systems (TCSs) genes and plasmids that transmit the mobilized colistin resistance resistant genes in E. coli strains. | 2023 | 36754367 |
| 4429 | 6 | 0.9998 | 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 |
| 9926 | 7 | 0.9998 | 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 |
| 4822 | 8 | 0.9998 | A Molecular Perspective on Colistin and Klebsiella pneumoniae: Mode of Action, Resistance Genetics, and Phenotypic Susceptibility. Klebsiella pneumoniae is a rod-shaped, encapsulated, Gram-negative bacteria associated with multiple nosocomial infections. Multidrug-resistant (MDR) K. pneumoniae strains have been increasing and the therapeutic options are increasingly limited. Colistin is a long-used, polycationic, heptapeptide that has regained attention due to its activity against Gram-negative bacteria, including the MDR K. pneumoniae strains. However, this antibiotic has a complex mode of action that is still under research along with numerous side-effects. The acquisition of colistin resistance is mainly associated with alteration of lipid A net charge through the addition of cationic groups synthesized by the gene products of a multi-genic regulatory network. Besides mutations in these chromosomal genes, colistin resistance can also be achieved through the acquisition of plasmid-encoded genes. Nevertheless, the diversity of molecular markers for colistin resistance along with some adverse colistin properties compromises the reliability of colistin-resistance monitorization methods. The present review is focused on the colistin action and molecular resistance mechanisms, along with specific limitations on drug susceptibility testing for K. pneumoniae. | 2021 | 34202395 |
| 4833 | 9 | 0.9998 | 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 |
| 9778 | 10 | 0.9998 | Antibiotic class with potent in vivo activity targeting lipopolysaccharide synthesis in Gram-negative bacteria. Here, we describe the identification of an antibiotic class acting via LpxH, a clinically unexploited target in lipopolysaccharide synthesis. The lipopolysaccharide synthesis pathway is essential in most Gram-negative bacteria and there is no analogous pathway in humans. Based on a series of phenotypic screens, we identified a hit targeting this pathway that had activity on efflux-defective strains of Escherichia coli. We recognized common structural elements between this hit and a previously published inhibitor, also with activity against efflux-deficient bacteria. With the help of X-ray structures, this information was used to design inhibitors with activity on efflux-proficient, wild-type strains. Optimization of properties such as solubility, metabolic stability and serum protein binding resulted in compounds having potent in vivo efficacy against bloodstream infections caused by the critical Gram-negative pathogens E. coli and Klebsiella pneumoniae. Other favorable properties of the series include a lack of pre-existing resistance in clinical isolates, and no loss of activity against strains expressing extended-spectrum-β-lactamase, metallo-β-lactamase, or carbapenemase-resistance genes. Further development of this class of antibiotics could make an important contribution to the ongoing struggle against antibiotic resistance. | 2024 | 38579010 |
| 4254 | 11 | 0.9998 | The forgotten Gram-negative bacilli: what genetic determinants are telling us about the spread of antibiotic resistance. Gram-negative bacilli have become increasingly resistant to antibiotics over the past 2 decades due to selective pressure from the extensive use of antibiotics in the hospital and community. In addition, these bacteria have made optimum use of their innate genetic capabilities to extensively mutate structural and regulatory genes of antibiotic resistance factors, broadening their ability to modify or otherwise inactivate antibiotics in the cell. The great genetic plasticity of bacteria have permitted the transfer of resistance genes on plasmids and integrons between bacterial species allowing an unprecedented dissemination of genes leading to broad-spectrum resistance. As a result, many Gram-negative bacilli possess a complicated set of genes encoding efflux pumps, alterations in outer membrane lipopolysaccharides, regulation of porins and drug inactivating enzymes such as beta-lactamases, that diminish the clinical utility of today's antibiotics. The cross-species mobility of these resistance genes indicates that multidrug resistance will only increase in the future, impacting the efficacy of existing antimicrobials. This trend toward greater resistance comes at a time when very few new antibiotics have been identified capable of controlling such multi-antibiotic resistant pathogens. The continued dissemination of these resistance genes underscores the need for new classes of antibiotics that do not possess the liability of cross-resistance to existing classes of drugs and thereby having diminished potency against Gram-negative bacilli. | 2006 | 16359640 |
| 4441 | 12 | 0.9998 | 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 |
| 4879 | 13 | 0.9998 | Prevalence of polymyxin resistance through the food chain, the global crisis. Antimicrobial resistance is one of the vital challenges facing global health today. Multi-drug resistant (MDR) infections are often treated with the narrow-spectrum drugs, colistin (polymyxin E) or polymyxin B, which are last-resort antibiotics for human therapeutics that are effective against Gram-negative bacteria. Unfortunately, resistance to these polymyxins has occurred because of selective pressure caused by the inappropriate use of those antibiotics, especially in farming. The mechanisms of resistance to polymyxins are mediated through intrinsic, mutational, or genetic alteration in chromosomal genes. The mechanism includes the regulatory network controlling chemical modifications of lipid A moiety of lipopolysaccharide, reducing the negative charge of lipid A and its affinity for polymyxins. Additionally, the unique mobile colistin/polymyxin B resistance (mcr) gene reported in Enterobacteriales is responsible for the horizontal dissemination of resistance to polymyxins via the food chain. There is now an urgent need to increase surveillance for detecting resistance to polymyxins. Therefore, this review presents an overview of presently available scientific literature on the mechanism of resistance to polymyxins, with their associated gene variants, evaluation methods, resistance transmission through the food chain via food bacteria, and related risk factors. We further focus on the significant implications of polymyxins usage in India and future views for food safety to preserve polymyxin activity. | 2022 | 35079146 |
| 4442 | 14 | 0.9998 | 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 |
| 4836 | 15 | 0.9998 | Genes and spectrum: the theoretical limits. Antibiotic resistance can result either from mutations within a chromosomal gene or from mobile genes imported from outside. In the last 15 years, some of these mobile genes have shown a propensity to adapt to successive antibiotic challenges, the most versatile being the class A beta-lactamases. The TEM and SHV beta-lactamase nuclei, usually after one initial critical mutation, allow a series of successive mutations that increase the spectrum to hydrolyze most cephalosporins. The class C beta-lactamases also show some versatility; while it migrates from the chromosome, subtle changes can occur in the gene to broaden the spectrum. Trimethoprim resistance has shown less adaptability in gram-negative bacteria, but in gram-positive organisms the plasmid has captured the chromosomal dihydrofolate reductase of Staphylococcus epidermidis, and a minimal number of changes have occurred that decrease the binding of trimethroprim. Other resistance mechanisms appear less adaptable, relying rather on the importation of new genes to cope with new challenges. | 1998 | 9710668 |
| 4835 | 16 | 0.9998 | 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 |
| 4402 | 17 | 0.9998 | 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 |
| 9779 | 18 | 0.9998 | Mechanisms of Polymyxin Resistance. Polymyxin antibiotics are increasingly being used as last-line therapeutic options against a number of multidrug resistant bacteria. These antibiotics show strong bactericidal activity against a range of Gram-negative bacteria, but with the increased use of these antibiotics resistant strains are emerging at an alarming rate. Furthermore, some Gram-negative species, such as Neisseria meningitidis, Proteus mirabilis and Burkholderia spp., are intrinsically resistant to the action of polymyxins. Most identified polymyxin resistance mechanisms in Gram-negative bacteria involve changes to the lipopolysaccharide (LPS) structure, as polymyxins initially interact with the negatively charged lipid A component of LPS. The controlled addition of positively charged residues such as 4-amino-(L)-arabinose, phosphoethanolamine and/or galactosamine to LPS results in a reduced negative charge on the bacterial surface and therefore reduced interaction between the polymyxin and the LPS. Polymyxin resistant species produce LPS that intrinsically contains one or more of these additions. While the genes necessary for most of these additions are chromosomally encoded, plasmid-borne phosphoethanolamine transferases (mcr-1 to mcr-8) have recently been identified and these plasmids threaten to increase the rate of dissemination of clinically relevant colistin resistance. Uniquely, Acinetobacter baumannii can also become highly resistant to polymyxins via spontaneous mutations in the lipid A biosynthesis genes lpxA, lpxC or lpxD such that they produce no LPS or lipid A. A range of other non-LPS-dependent polymyxin resistance mechanisms has also been identified in bacteria, but these generally result in only low levels of resistance. These include increased anionic capsular polysaccharide production in Klebsiella pneumoniae, expression of efflux systems such as MtrCDE in N. meningitidis, and altered expression of outer membrane proteins in a small number of species. | 2019 | 31364071 |
| 4866 | 19 | 0.9998 | Resistance to polymyxins in Gram-negative organisms. Polymyxins have recently been re-introduced into the therapeutic arsenal to combat infections caused by multidrug-resistant Gram-negative bacteria. However, the emergence of strains resistant to these last-resort drugs is becoming a critical issue in a growing number of countries. Both intrinsic and transferable mechanisms of polymyxin resistance have been characterised. These mechanisms as well as the epidemiological data regarding four relevant bacterial pathogens (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa) are considered in this review. A special focus is made on plasmid-mediated resistance and the spread of mcr genes. | 2017 | 28163137 |