Plasmid-borne AmpC beta-lactamases. - Related Documents




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484201.0000Plasmid-borne AmpC beta-lactamases. Historically, it was thought that ampC genes encoding class C beta-lactamases were located solely on the chromosome but, within the last 12 years, an increasing number of ampC genes have been found on plasmids. These have mostly been acquired by ampC-deficient pathogenic bacteria, which consequently are supplied with new and additional resistance phenotypes. This review discusses the phylogenetic origin of the plasmid-encoded AmpC beta-lactamases, their occurrence, and mode of spread, as well as their hydrolytic properties.200212166675
484510.9999The changing epidemiology of resistance. Antibiotic resistance is now a linked global problem. Dispersion of successful clones of multidrug resistant (MDR) bacteria is common, often via the movement of people. Local evolution of MDR bacteria is also important under the pressure of excessive antibiotic use, with horizontal gene transfer providing the means by which genes such as bla(CTX-M) spread amongst different bacterial species and strains. Beta-lactamase production is a common resistance mechanism in Gram-negative bacteria, and the rapid dissemination of novel genes reflects their evolution under the selective pressure of antibiotic usage. Many Enterobacteriaceae now carry broad-spectrum beta-lactamases such as CTX-M, with particular genotypes associated with different geographical regions. The spread of these enzymes has compromised the clinical utility of a number of beta-lactam classes and with the spread of genes such as bla(KPC), carbapenems may be increasingly compromised in the future. High-level fluoroquinolone resistance (mainly caused by gyrA mutations) has also been shown to be associated with CTX-M and CMY-type enzymes, commonly due to co-carriage on conjugative plasmids of the gene for the aminoglycoside-inactivating enzyme AAC-6(1)-Ib-cr and qnr genes (which confer low-level resistance), allowing the easy selection of gyrA mutants in the host strain. Resistance in Gram-positive bacteria is also widely distributed and increasing, with the emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) blurring the distinction between hospital and community strains. Antibiotic use and environmental factors all have a role in the emergence and spread of resistance. This article reviews some of the new mechanisms and recent trends in the global spread of MDR bacteria.200919675017
484620.9999Mobile fosfomycin resistance genes in Enterobacteriaceae-An increasing threat. Antimicrobial resistance is one of the major threats to the health and welfare of both humans and animals. The shortage of new antimicrobial agents has led to the re-evaluation of old antibiotics such as fosfomycin as a potential regimen for treating multidrug-resistant bacteria especially extended-spectrum-beta-lactamase- and carbapenemase-producing Enterobacteriaceae. Fosfomycin is a broad-spectrum bactericidal antibiotic that inhibits the initial step of the cell wall biosynthesis. Fosfomycin resistance can occur due to mutation in the drug uptake system or by the acquisition of fosfomycin-modifying enzymes. In this review, we focus on mobile fosfomycin-resistant genes encoding glutathione-S-transferase which are mainly responsible for fosfomycin resistance in Enterobacteriaceae, that is, fosA and its subtypes, fosC2, and the recently described fosL1-L2. We summarized the proposed origins of the different resistance determinants and highlighted the different plasmid types which are attributed to the dissemination of fosfomycin-modifying enzymes. Thereby, IncF and IncN plasmids play a predominant role. The detection of mobile fosfomycin-resistant genes in Enterobacteriaceae has increased in recent years. Similar to the situation in (East) Asia, the most frequently detected fosfomycin-resistant gene in Europe is fosA3. Mobile fosfomycin-resistant genes have been detected in isolates of human, animal, food, and environmental origin which leads to a growing concern regarding the risk of spread of such bacteria, especially Escherichia coli and Salmonella, at the human-animal-environment interface.202033128341
484030.9999Beta-lactam antibiotics and selection of resistance: speculation on the evolution of R-plasmids. In this paper we describe two genetic mechanisms which are responsible for the development of resistance to third-generation cephalosporins. One is a plasmid-mediated mechanism involving a mutation in the SHV-1-gene towards the production of the beta-lactamase SHV-2 which has increased affinity for these antibiotics. The other is chromosomally mediated and occurs at high frequency by mutation of inducible beta-lactamase-genes, leading to derepressed production of the enzyme. Together with other examples of resistance genes these two mechanisms lead us to a hypothesis about the evolution of beta-lactamase producing bacteria.19863542929
446440.9999Class 1 integrons, gene cassettes, mobility, and epidemiology. Integrons are genetic elements that, although unable to move themselves, contain gene cassettes that can be mobilized to other integrons or to secondary sites in the bacterial genome. The majority of approximately 60 known gene cassettes encode resistance to antibiotics. Recently, a number of gene cassettes encoding extended-spectrum beta-lactamases or carbapenemases have been described. Up to at least five cassettes may be present in an integron, which leads to multiresistance. Frequently, more than one integron is observed within the same bacterial cell. Integrons are widespread in their species distribution. Although integrons are normally reported from Enterobacteriaceae and other gram-negative bacteria, an integron has been described in Corynebacterium glutamicum, a gram-positive species. The gene cassette in this integron showed even higher expression when compared to the expression in Escherichia coli. Integrons have been reported from all continents and are found frequently. The widespread occurrence of integrons is thought to be due to their association with transposon plasmids, conjugative plasmids, or both. Integrons form an important source for the spread of antibiotic resistance, at least in gram-negative bacteria but also potentially in gram-positive bacteria. The aim of this review is to describe the versatility of integrons, especially their mobility and their ability to collect resistance genes.199910614949
484450.9999Genetic basis of molecular mechanisms in β-lactam resistant gram-negative bacteria. Antibiotic-resistant bacteria are considered one of the major global threats to human and animal health. The most harmful among the resistant bacteria are β-lactamase producing Gram-negative species (β-lactamases). β-lactamases constitute a paradigm shift in the evolution of antibiotic resistance. Therefore, it is imperative to present a comprehensive review of the mechanisms responsible for developing antimicrobial resistance. Resistance due to β-lactamases develops through a variety of mechanisms, and the number of resistant genes are involved that can be transferred between bacteria, mostly via plasmids. Over time, these new molecular-based resistance mechanisms have been progressively disclosed. The present review article provides information on the recent findings regarding the molecular mechanisms of resistance to β-lactams in Gram-negative bacteria, including CTX-M-type ESBLs with methylase activity, plasmids harbouring phages with β-lactam resistance genes, the co-presence of β-lactam resistant genes of unique combinations and the presence of β-lactam and non-β-lactam antibiotic-resistant genes in the same bacteria. Keeping in view, the molecular level resistance development, multifactorial and coordinated measures may be taken to counter the challenge of rapidly increasing β-lactam resistance.202134119627
484360.9999The Efficacy of Isolated Bacteriophages from Pig Farms against ESBL/AmpC-Producing Escherichia coli from Pig and Turkey Farms. Extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases are plasmid (but also chromosomally) encoded enzymes found in Enterobacteriaceae, determining resistance to a variety of important antibiotics including penicillins, cephalosporins, and monobactams. In recent decades, the prevalence of ESBL/AmpC-producing bacteria has increased rapidly across the world. Here, we evaluate the potential use of bacteriophages in terms of a reduction of antibiotic-resistant bacteria in healthy animals. The aim of our studies was to isolate bacteriophages capable of destroying ESBL/AmpC-producing Escherichia coli isolated from livestock habitats. The efficacy of isolated phages against ESBL/AmpC E. coli strains varies, but creation of a phage cocktail with broad activity spectrum is possible. This may indicate that the role of phages may not be limited to phage therapy, but bacterial viruses may also be applied against spread of bacteria with antibiotic resistance genes in the environment. We also addressed the hypothesis, that phages, effective for therapeutic purposes may be isolated from distant places and even from different environments other than the actual location of the targeted bacteria. This may be beneficial for practical purposes, as the construction of effective phage preparations does not require access to disease outbreaks.201728405193
484770.9998Escherichia coli β-Lactamases: What Really Matters. Escherichia coli strains belonging to diverse pathotypes have increasingly been recognized as a major public health concern. The β-lactam antibiotics have been used successfully to treat infections caused by pathogenic E. coli. However, currently, the utility of β-lactams is being challenged severely by a large number of hydrolytic enzymes - the β-lactamases expressed by bacteria. The menace is further compounded by the highly flexible genome of E. coli, and propensity of resistance dissemination through horizontal gene transfer and clonal spread. Successful management of infections caused by such resistant strains requires an understanding of the diversity of β-lactamases, their unambiguous detection, and molecular mechanisms underlying their expression and spread with regard to the most relevant information about individual bacterial species. Thus, this review comprises first such effort in this direction for E. coli, a bacterial species known to be associated with production of diverse classes of β-lactamases. The review also highlights the role of commensal E. coli as a potential but under-estimated reservoir of β-lactamases-encoding genes.201627065978
154880.9998Metallo-beta-lactamases of Pseudomonas aeruginosa--a novel mechanism resistance to beta-lactam antibiotics. Since about twenty years, following the introduction into therapeutic of news beta-lactam antibiotics (broad-spectrum cephalosporins, monobactams and carbapenems), a very significant number of new beta-lactamases appeared. These enzymes confer to the bacteria which put them, the means of resisting new molecules. The genetic events involved in this evolution are of two types: evolution of old enzymes by mutation and especially appearance of new genes coming for some, from bacteria of the environment. Numerous mechanisms of enzymatic resistance to the carbapenems have been described in Pseudomonas aeruginosa. The important mechanism of inactivation carbapenems is production variety of b-lactam hydrolysing enzymes associated to carbapenemases. The metallo-beta-enzymes (IMP, VIM, SPM, GIM types) are the most clinically significant carbapenemases. P. aeruginosa posses MBLs and seem to have acquired them through transmissible genetic elements (plasmids or transposons associated with integron) and can be transmission to other bacteria. They have reported worldwide but mostly from South East Asia and Europe. The enzymes, belonging to the molecular class B family, are the most worrisome of all beta-lactamases because they confer resistance to carbapenems and all the beta-lactams (with the exception of aztreonam) and usually to aminoglycosides and quinolones. The dissemination of MBLs genes is thought to be driven by regional consumption of extended--spectrum antibiotics (e.g. cephalosporins and carbapenems), and therefore care must be taken that these drugs are not used unnecessarily.200818519228
988390.9998Plasmids in Gram negatives: molecular typing of resistance plasmids. A plasmid is defined as a double stranded, circular DNA molecule capable of autonomous replication. By definition, plasmids do not carry genes essential for the growth of host cells under non-stressed conditions but they have systems which guarantee their autonomous replication also controlling the copy number and ensuring stable inheritance during cell division. Most of the plasmids confer positively selectable phenotypes by the presence of antimicrobial resistance genes. Plasmids evolve as an integral part of the bacterial genome, providing resistance genes that can be easily exchanged among bacteria of different origin and source by conjugation. A multidisciplinary approach is currently applied to study the acquisition and spread of antimicrobial resistance in clinically relevant bacterial pathogens and the established surveillance can be implemented by replicon typing of plasmids. Particular plasmid families are more frequently detected among Enterobacteriaceae and play a major role in the diffusion of specific resistance genes. For instance, IncFII, IncA/C, IncL/M, IncN and IncI1 plasmids carrying extended-spectrum beta-lactamase genes and acquired AmpC genes are currently considered to be "epidemic resistance plasmids", being worldwide detected in Enterobacteriaceae of different origin and sources. The recognition of successful plasmids is an essential first step to design intervention strategies preventing their spread.201121992746
9928100.9998The emergence and implications of metallo-beta-lactamases in Gram-negative bacteria. The increase in Gram-negative broad-spectrum antibiotic resistance is worrisome, particularly as there are few, if any, ''pipeline'' antimicrobial agents possessing suitable activity against Pseudomonas spp. or Acinetobacter spp. The increase in resistance will be further enhanced by the acquisition of metallo-beta-lactamase (MBL) genes that can potentially confer broad-spectrum beta-lactam resistance. These genes encode enzymes that can hydrolyse all classes of beta-lactams and the activity of which cannot be neutralised by beta-lactamase inhibitors. MBL genes are often associated with aminoglycoside resistant genes and thus bacteria that possess MBL genes are often co-resistant to aminoglycosides, further compromising therapeutic regimes. Both types of genes can be found as gene cassettes carried by integrons that in turn are embedded within transposons providing a highly ambulatory genetic element. The dissemination of MBL genes is typified by the spread of blaVIM-2, believed to originate from a Portuguese patient in 1995, and is now present in over 20 counties. The increase in international travel is likely to be a contributory factor for the ascendancy of mobile MBL genes as much as the mobility among individual bacteria. Fitness, acquisition and host dependency are key areas that need to be addressed to enhance our understanding of how antibiotic resistance spreads. There is also a pressing need for new, and hopefully novel, compounds active against pan-resistant Gram-negative bacteria--a growing problem that needs to be addressed by both government and industry.200516209700
5016110.9998Broad-spectrum β-lactamases among Enterobacteriaceae of animal origin: molecular aspects, mobility and impact on public health. Broad-spectrum β-lactamase genes (coding for extended-spectrum β-lactamases and AmpC β-lactamases) have been frequently demonstrated in the microbiota of food-producing animals. This may pose a human health hazard as these genes may be present in zoonotic bacteria, which would cause a direct problem. They can also be present in commensals, which may act as a reservoir of resistance genes for pathogens causing disease both in humans and in animals. Broad-spectrum β-lactamase genes are frequently located on mobile genetic elements, such as plasmids, transposons and integrons, which often also carry additional resistance genes. This could limit treatment options for infections caused by broad-spectrum β-lactam-resistant microorganisms. This review addresses the growing burden of broad-spectrum β-lactam resistance among Enterobacteriaceae isolated from food, companion and wild animals worldwide. To explore the human health hazard, the diversity of broad-spectrum β-lactamases among Enterobacteriaceae derived from animals is compared with respect to their presence in human bacteria. Furthermore, the possibilities of the exchange of genes encoding broad-spectrum β-lactamases - including the exchange of the transposons and plasmids that serve as vehicles for these genes - between different ecosystems (human and animal) are discussed.201020030731
1545120.9998Carbapenemases: Partners in crime. Carbapenemases, β-lactamases that inactivate carbapenems and most β-lactam antibiotics, are most widely known for their ability to confer resistance to β-lactams. They include serine carbapenemases, such as the widespread KPC family of enzymes, and the metallo-β-lactamases that contain the IMP, NDM and VIM enzyme families acquired by Gram-negative bacteria on transferable elements. These enzymes are almost always produced by organisms that encode at least one other β-lactamase, with as many as eight different β-lactamase genes detected in a single isolate. This consortium of β-lactamases includes a full spectrum of molecular and biochemical characteristics, providing the producing organism with a range of catalytic activities. In addition to the variety of β-lactamases found in carbapenemase-producing Gram-negative pathogens are multiple other resistance factors, especially aminoglycoside-modifying enzymes and 16S rRNA methylases that confer resistance to aminoglycosides. Other acquired genes encode fluoroquinolone, trimethoprim, sulfonamide, rifampicin and chloramphenicol resistance determinants on mobile elements that travel together with β-lactamase genes. Thus, the recent proliferation of transferable carbapenemases serves to magnify resistance to virtually all antibiotic classes. Judicial use of current antibiotics and a quest for novel antibacterial agents are necessary, as multidrug-resistant bacteria continue to multiply.201327873609
5030130.9998Characterization of ESBL disseminating plasmids. Bacteria producing extended-spectrum β-lactamases (ESBLs) constitute a globally increasing problem that contributes to treatment complications and elevated death rates. The extremely successful dissemination by ESBL-producing Enterobacteriaceae during the latest decades is a result of the combination of mobilization, evolution and horizontal spread of β-lactamase genes on plasmids. In parallel, spread of these plasmids to particularly well-adapted bacterial clones (outbreak clones) has expanded. In this review we describe ESBL-producing bacteria and the genetic mechanisms for dissemination of ESBL resistance. We describe available methodology for studying plasmids and the importance of including plasmids in epidemiological typing as natural parts of the organisms. Plasmids play a fundamental role in how resistance arises and disseminates.201626135711
4860140.9998The rise of carbapenem-resistant Acinetobacter baumannii. Acinetobacter spp. are Gram-negative bacteria that have become one of the most difficult pathogens to treat. The species A. baumannii, largely unknown 30 years ago, has risen to prominence particularly because of its ability to cause infections in immunocompromised patients. It is now a predominant pathogen in many hospitals as it has acquired resistance genes to virtually all antibiotics capable of treating Gram-negative bacteria, including the fluoroquinolones and the cephalosporins. Some members of the species have accumulated these resistance genes in large resistance islands, located in a "hot-spot" within the bacterial chromosome. The only conventional remaining treatment options were the carbapenems. However, A. baumannii possesses an inherent class D β-lactamase gene (blaOXA-51-like) that can have the ability to confer carbapenem resistance. Additionally, mechanisms of carbapenem resistance have emerged that derive from the importation of the distantly related class D β-lactamase genes blaOXA-23 and blaOXA-58. Although not inducible, the expression of these genes is controlled by mobile promoters carried on ISAba elements. It has also been found that other resistance genes including the chromosomal class C β-lactamase genes conferring cephalosporin resistance are controlled in the same manner. Colistin is now considered to be the final drug capable of treating infections caused by carbapenem-resistant A. baumannii; however, strains are now being isolated that are resistant to this antibiotic as well. The increasing inability to treat infections caused by A. baumannii ensures that this pathogen more than ranks with MRSA or Clostridium difficile as a threat to modern medicine.201322894617
4957150.9998Plasmid-mediated quinolone resistance gene detected in Escherichia coli from cattle. Fluoroquinolones resistance in bacteria can be due to chromosomal and plasmid-mediated mechanisms. Of growing concern is the acquisition of genes encoding quinolone resistance in combination with other resistance mechanisms such as extended-spectrum beta-lactamases. In this study we describe the identification of an isolate of Escherichia coli from cattle which carried qnrS1 in combination with a blaCTX-M gene, although they were not co-localised on the same plasmid. In addition, using a DNA array it was possible to identify several other antimicrobial resistance genes in this isolate. This is the first report of a qnr gene in E. coli from cattle in the UK and highlights the need for surveillance of these emerging resistance mechanisms.201120884136
4836160.9998Genes 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.19989710668
9882170.9998Integrons in Enterobacteriaceae: diversity, distribution and epidemiology. Integrons are versatile gene acquisition systems that allow efficient capturing of exogenous genes and ensure their expression. Various classes of integrons possessing a wide variety of gene cassettes are ubiquitously distributed in enteric bacteria worldwide. The epidemiology of integrons associated multidrug resistance in Enterobacteriaceae is rapidly evolving. In the past two decades, the incidence of integrons in enteric bacteria has increased drastically with evolution of multiple gene cassettes, novel gene arrangements and complex chromosomal integrons such as Salmonella genomic islands. This review focuses on the distribution, versatility, spread and global trends of integrons among important members of the Enterobacteriaceae, including Escherichia coli, Klebsiella, Shigella and Salmonella, which are known to cause infections globally. Such a comprehensive understanding of integron-associated antibiotic resistance, their role in the spread of such resistance traits and their clinical relevance especially with regard to each genus individually is paramount to contain the global spread of antibiotic resistance.201829038087
5015180.9998beta-Lactam resistance and beta-lactamases in bacteria of animal origin. beta-Lactams are among the most clinically important antimicrobials in both human and veterinary medicine. Bacterial resistance to beta-lactams has been increasingly observed in bacteria, including those of animal origin. The mechanisms of beta-lactam resistance include inaccessibility of the drugs to their target, target alterations and/or inactivation of the drugs by beta-lactamases. The latter contributes predominantly to beta-lactam resistance in Gram-negative bacteria. A variety of beta-lactamases have been identified in bacteria derived from food-producing and companion animals and may further serve as a reservoir for beta-lactamase-producing bacteria in humans. While this review mainly describes beta-lactamases from animal-derived Escherichia coli and Salmonella spp., beta-lactamases from animal-derived Campylobacter spp., Enterococcus spp., Staphylococcus spp. and other pathogens are also discussed. Of particular concern are the increasingly-isolated plasmid-encoded AmpC-type CMY and extended-spectrum CTX-M beta-lactamases, which mediate acquired resistance to extended-spectrum beta-lactams. The genes encoding these enzymes often coexist with other antimicrobial resistance determinants and can also be associated with transposons/integrons, increasing the potential enrichment of multidrug resistant bacteria by multiple antimicrobial agents as well as dissemination of the resistance determinants among bacterial species. Characterization of beta-lactam-resistant animal-derived bacteria warrants further investigation of the type and distribution of beta-lactamases in bacteria of animal origin and their potential impact on human medicine.200717306475
4925190.9998Assessing genetic diversity and similarity of 435 KPC-carrying plasmids. The global spread and diversification of multidrug-resistant Gram-negative (MRGN) bacteria poses major challenges to healthcare. In particular, carbapenem-resistant Klebsiella pneumoniae strains have been frequently identified in infections and hospital-wide outbreaks. The most frequently underlying resistance gene (bla(KPC)) has been spreading over the last decade in the health care setting. bla(KPC) seems to have rapidly diversified and has been found in various species and on different plasmid types. To review the progress and dynamics of this diversification, all currently available KPC plasmids in the NCBI database were analysed in this work. Plasmids were grouped into 257 different representative KPC plasmids, of which 79.4% could be clearly assigned to incompatibility (Inc) group or groups. In almost half of all representative plasmids, the KPC gene is located on Tn4401 variants, emphasizing the importance of this transposon type for the transmission of KPC genes to other plasmids. The transposons also seem to be responsible for the occurrence of altered or uncommon fused plasmid types probably due to incomplete transposition. Moreover, many KPC plasmids contain genes that encode proteins promoting recombinant processes and mutagenesis; in consequence accelerating the diversification of KPC genes and other colocalized resistance genes.201931375735