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982100.9981Mercury resistance (mer) operons in enterobacteria. Mercury resistance is found in many genera of bacteria. Common amongst enterobacteria are transposons related to Tn21, which is both mercuric ion- and streptomycin-/spectinomycin- and sulphonamide-resistant. Other Tn21-related transposons often have different antibiotic resistances compared with Tn21, but share many non-antibiotic-resistance genes with it. In this article we discuss possible mechanisms for the evolution of Tn21 and related genetic elements.200212196175
413210.9981Mobilization of transposons : rationale and techniques for detection. The ability to share genetic information with other bacteria represents one of the most important adaptive mechanisms available to bacteria pathogenic for humans. The exchange of many different types of genetic information appears to occur frequently and exchange of determinants responsible for antimicrobial resistance is the best studied, since the movements of resistance determinants are easy to follow and the clinical importance of resistance dissemination is so great. The most common vehicles by which bacteria exchange resistance determinants are plasmids and transposons.200121374427
375420.9981Cancer departments as a source of resistant bacteria and fungi? Antimicrobial resistance increases worldwide. Among many factors, such as clonal spread of genes of resistance among and intra species, local epidemiology, nosocomial transmission, also consumption of antimicrobials may be responsible. Cancer departments, mainly in centers treating hematologic malignancies and organizing bone marrow transplantation (BMT) are known to have extensive consumption of either prophylactically or therapeutically administered antibiotics and antifungals. It is worthy to remember, that first strains of quinolone resistant E. coli, vancomycin resistant enterococci and staphylococci and fluconazol-resistant Candida albicans appeared in the patients treated for cancer with antineoplastic chemotherapy, resulting in profound granulocytopenia. Therefore, assessment of risks of antibiotic prophylaxis with quinolones and azoles and extensive use of empiric therapy with glycopeptides and polyenes needs to be considered. Intensive prophylactic strategies should be limited to group of high risk, leukemic patients or BMT recipients.199910355526
35830.9980Resistance factors in anaerobic bacteria. Resistance transfer factors have been described in both Bacteroides and clostridia. The clindamycin (Cln) resistance transfer factors from the Bacteroides fragilis group of organisms have been best studied, including our own plasmid pBFTM10. The clindamycin resistance determinant (Cln X) of pBFTM10 can be detected in 90% of Cln resistant Bacteroides isolated from dispersed geographical areas. This determinant can be located in the chromosome and on plasmids. Recent studies from our laboratory have shown that the Cln X genes of pBFTM 10 are carried on a compound transposon, Tn4400. Bacteroides plasmids have been cloned in Escherichia coli and shuttle vectors have been developed that allow transfers of DNA from E. coli back to B. fragilis, using the broad host range plasmid RK2 to supply essential conjugation functions. We have shown that shuttle vectors containing pBFTM 10 can be retransferred from B. fragilis back to E. coli. In addition, a tetracycline transfer element from B. fragilis strain TM230 is able to promote high frequency conjugation between B. fragilis and E. coli. The results of these investigations indicate that Bacteroides has efficient mechanisms to exchange genetic material and that genetic exchange can occur between Bacteroides and E. coli, which exist in intimate contact in the human colon.19863029859
414840.9980Plasmids in the environment. Bacterial plasmids existed in bacteria before the antibiotic era but their presence was brought into prominence by the use of antibiotics which selected for antibiotic resistant strains. Subsequently, the range of genes carried on plasmids was shown to extend far beyond those coding for antibiotic resistance. Any consideration of plasmids in the environment, therefore, must include all plasmids whether or not they are genetically linked with antibiotic resistance. Antibiotic resistant bacteria may be found in the environment either by contamination with excreta from man and animals in which the strains were selected, or by their selection within the environment by antibiotics synthesized in situ or reaching the environment in an undegraded form in sewage from man and animals, or from industry. Other agents, also contaminating the environment, exert a selective pressure such as heavy metals in industrial effluents which select for metal resistance. This paper reviews the incidences and role of plasmids in various habitats including natural waters, soil, pastures, farm wastes, and human sewage from both hospitalised and other populations. Aspects of plasmid ecology, their biological role, and the transmissibility of genetic material between bacteria within the environment are considered. Two recent studies in Bristol, UK, are reported. The first was a genetic study on Escherichia coli isolates from calf slurry. Various DNA probes were used to determine the extent of gene exchange between the various serotypes within the natural environment. The second was a preliminary study to determine the stability of a recombinant plasmid, in a wild strain of Escherichia coli of pig origin, after its release into a semi-contained farm situation. It is now recognized that plasmids are widely distributed in bacterial populations in terrestrial and aquatic environments. Many have been detected by their carriage of genes coding for antibiotic or heavy metal resistance. Others, mainly cryptic in nature, have been demonstrated by plasmid profile studies on isolates from various habitats. Plasmids were shown to be present in a relatively few bacteria deposited in culture collections prior to the antibiotic era. Subsequently, the increased prevalence of R plasmids in bacteria in most ecosystems were due mainly to the selective pressure imposed by the use of antibiotics. This pressure may have been exerted either in the environment in which the strains were found or elsewhere, the environment subsequently being contaminated by antibiotic resistant bacteria.(ABSTRACT TRUNCATED AT 400 WORDS)19883074480
376950.9980Clostridioides difficile as a Dynamic Vehicle for the Dissemination of Antimicrobial-Resistance Determinants: Review and In Silico Analysis. The present paper is divided into two parts. The first part focuses on the role of Clostridioides difficile in the accumulation of genes associated with antimicrobial resistance and then the transmission of them to other pathogenic bacteria occupying the same human intestinal niche. The second part describes an in silico analysis of the genomes of C. difficile available in GenBank, with regard to the presence of mobile genetic elements and antimicrobial resistance genes. The diversity of the C. difficile genome is discussed, and the current status of resistance of the organisms to various antimicrobial agents is reviewed. The role of transposons associated with antimicrobial resistance is appraised; the importance of plasmids associated with antimicrobial resistance is discussed, and the significance of bacteriophages as a potential shuttle for antimicrobial resistance genes is presented. In the in silico study, 1101 C. difficile genomes were found to harbor mobile genetic elements; Tn6009, Tn6105, CTn7 and Tn6192, Tn6194 and IS256 were the ones more frequently identified. The genes most commonly harbored therein were: ermB, blaCDD, vanT, vanR, vanG and vanS. Tn6194 was likely associated with resistance to erythromycin, Tn6192 and CTn7 with resistance to the β-lactams and vancomycin, IS256 with resistance to aminoglycoside and Tn6105 to vancomycin.202134202117
414560.9980Antimicrobial Resistance among Staphylococci of Animal Origin. Antimicrobial resistance among staphylococci of animal origin is based on a wide variety of resistance genes. These genes mediate resistance to many classes of antimicrobial agents approved for use in animals, such as penicillins, cephalosporins, tetracyclines, macrolides, lincosamides, phenicols, aminoglycosides, aminocyclitols, pleuromutilins, and diaminopyrimidines. In addition, numerous mutations have been identified that confer resistance to specific antimicrobial agents, such as ansamycins and fluoroquinolones. The gene products of some of these resistance genes confer resistance to only specific members of a class of antimicrobial agents, whereas others confer resistance to the entire class or even to members of different classes of antimicrobial agents, including agents approved solely for human use. The resistance genes code for all three major resistance mechanisms: enzymatic inactivation, active efflux, and protection/modification/replacement of the cellular target sites of the antimicrobial agents. Mobile genetic elements, in particular plasmids and transposons, play a major role as carriers of antimicrobial resistance genes in animal staphylococci. They facilitate not only the exchange of resistance genes among members of the same and/or different staphylococcal species, but also between staphylococci and other Gram-positive bacteria. The observation that plasmids of staphylococci often harbor more than one resistance gene points toward coselection and persistence of resistance genes even without direct selective pressure by a specific antimicrobial agent. This chapter provides an overview of the resistance genes and resistance-mediating mutations known to occur in staphylococci of animal origin.201829992898
414470.9980The diversity of antimicrobial resistance genes among staphylococci of animal origin. Staphylococci of animal origin harbor a wide variety of resistance genes. So far, more than 40 different resistance genes have been identified in staphylococci from animals. This includes genes that confer resistance to virtually all classes of antimicrobial agents approved for use in animals, such as penicillins, cephalosporins, tetracyclines, macrolides, lincosamides, phenicols, aminoglycosides, aminocyclitols, pleuromutilins, and diaminopyrimidines. The gene products of some of these resistance genes confer resistance to only specific members of a class of antimicrobial agents, whereas others confer resistance to the entire class or even to members of different classes of antimicrobial agents. The resistance mechanisms specified by the resistance genes fall into three major categories: (i) enzymatic inactivation, (ii) active efflux, or (iii) protection/modification/replacement of the cellular target sites of the antimicrobial agents. Mobile genetic elements, in particular plasmids and transposons, play a major role as carriers of antimicrobial resistance genes in animal staphylococci. They facilitate the exchange of resistance genes with staphylococci of human origin but also with other Gram-positive bacteria.201323499306
413480.9980Plasmid-Mediated Antimicrobial Resistance in Staphylococci and Other Firmicutes. In staphylococci and other Firmicutes, resistance to numerous classes of antimicrobial agents, which are commonly used in human and veterinary medicine, is mediated by genes that are associated with mobile genetic elements. The gene products of some of these antimicrobial resistance genes confer resistance to only specific members of a certain class of antimicrobial agents, whereas others confer resistance to the entire class or even to members of different classes of antimicrobial agents. The resistance mechanisms specified by the resistance genes fall into any of three major categories: active efflux, enzymatic inactivation, and modification/replacement/protection of the target sites of the antimicrobial agents. Among the mobile genetic elements that carry such resistance genes, plasmids play an important role as carriers of primarily plasmid-borne resistance genes, but also as vectors for nonconjugative and conjugative transposons that harbor resistance genes. Plasmids can be exchanged by horizontal gene transfer between members of the same species but also between bacteria belonging to different species and genera. Plasmids are highly flexible elements, and various mechanisms exist by which plasmids can recombine, form cointegrates, or become integrated in part or in toto into the chromosomal DNA or into other plasmids. As such, plasmids play a key role in the dissemination of antimicrobial resistance genes within the gene pool to which staphylococci and other Firmicutes have access. This chapter is intended to provide an overview of the current knowledge of plasmid-mediated antimicrobial resistance in staphylococci and other Firmicutes.201426104453
447290.9980Conjugative plasmids in bacteria of the 'pre-antibiotic' era. Antibiotic resistance is common in bacteria that cause disease in man and animals and is usually determined by plasmids. The prevalence of such plasmids, and the range of drugs to which they confer resistance, have increased greatly in the past 25 yr. It has become clear from work in many laboratories that plasmids have acquired resistance genes, of ultimately unknown origin, as insertions into their circular DNA. The intensive use of antibiotics since their introduction in the 1940s can explain the spread of plasmids that have acquired such genes but little is known of the incidence of plasmids in pathogenic bacteria before the widespread use of antibiotics in medicine. E.D.G. Murray collected strains of Enterobacteriaceae from 1917 to 1954; we now report that 24% of these encode information for the transfer of DNA from one bacterium to another. From at least 19% of the strains, conjugative plasmids carrying no antibiotic resistance were transferred to Escherichia coli K-12.19836835408
4216100.9980Antimicrobial Resistance in the Food Chain in the European Union. Consumers require safety foods but without losing enough supply and low prices. Food concerns about antimicrobial residues and antimicrobial-resistant (AMR) bacteria are not usually appropriately separated and could be perceived as the same problem. The monitoring of residues of antimicrobials in animal food is well established at different levels (farm, slaughterhouse, and industry), and it is preceded by the legislation of veterinary medicines where maximum residues limits are required for medicines to be used in food animal. Following the strategy of the World Health Organization, one of the proposed measures consists in controlling the use of critical antibiotics. The European Union surveillance program currently includes the animal species with the highest meat production (pigs, chickens, turkeys, and cattle) and the food derived from them, investigating antimicrobial resistance of zoonotic (Salmonella and Campylobacter) and indicator (Escherichia coli and enterococci) bacteria. AMR mechanisms encoded by genes have a greater impact on transfer than mutations. Sometimes these genes are found in mobile genetic elements such as plasmids, transposons, or integrons, capable of passing from one bacterium to another by horizontal transfer. It is important to know that depending on how the resistance mechanism is transferred, the power of dissemination is different. By vertical transfer of the resistance gene, whatever its origin, will be transmitted to the following generations. In the case of horizontal transfer, the resistance gene moves to neighboring bacteria and therefore the range of resistance can be much greater.201830077219
4174110.9980The role of conjugative transposons in spreading antibiotic resistance between bacteria that inhabit the gastrointestinal tract. There is huge potential for genetic exchange to occur within the dense, diverse anaerobic microbial population inhabiting the gastrointestinal tract (GIT) of humans and animals. However, the incidence of conjugative transposons (CTns) and the antibiotic resistance genes they carry has not been well studied among this population. Since any incoming bacteria, including pathogens, can access this reservoir of genes, this oversight would appear to be an important one. Recent evidence has shown that anaerobic bacteria native to the rumen or hindgut harbour both novel antibiotic resistance genes and novel conjugative transposons. These CTns, and previously characterized CTns, can be transferred to a wide range of commensal bacteria under laboratory and in vivo conditions. The main evidence that gene transfer occurs widely in vivo between GIT bacteria, and between GIT bacteria and pathogenic bacteria, is that identical resistance genes are present in diverse bacterial species from different hosts.200212568333
4173120.9980Evidence for natural horizontal transfer of tetQ between bacteria that normally colonize humans and bacteria that normally colonize livestock. Though numerous studies have shown that gene transfer occurs between distantly related bacterial genera under laboratory conditions, the frequency and breadth of horizontal transfer events in nature remain unknown. Previous evidence for natural intergeneric transfers came from studies of genes in human pathogens, bacteria that colonize the same host. We present evidence that natural transfer of a tetracycline resistance gene, tetQ, has occurred between bacterial genera that normally colonize different hosts. A DNA sequence comparative approach was taken to examine the extent of horizontal tetQ dissemination between species of Bacteroides, the predominant genus of the human colonic microflora, and between species of Bacteroides and of the distantly related genus Prevotella, a predominant genus of the microflora of the rumens and intestinal tracts of farm animals. Virtually identical tetQ sequences were found in a number of isolate pairs differing in taxonomy and geographic origin, indicating that extensive natural gene transmission has occurred. Among the exchange events indicated by the evidence was the very recent transfer of an allele of tetQ usually found in Prevotella spp. to a Bacteroides fragilis strain.19947944364
9828130.9980Antibiotic resistance: genetic mechanisms and mobility. Based on the current knowledge, resistance genes seems mainly to originate in the organisms which produce antibiotics (Davies 1994). We lack considerably in the understanding of how these genes were transferred to pathogenic bacteria, and due to the enormous diversity of e.g. the soil flora, it is doubtful that we will ever obtain more that a faint picture of this. In Gram negative bacteria, more and more resistance genes are demonstrated to be located in integrons (e.g. beta-lactamase and streptomycin resistance genes in Salmonella Typhimurium DT104 (Sandvang et al. in press)). Integrons seem primarily to act as insertion sites for resistance genes. The origin of integrons as well as the resistance gene cassettes that are the other essential element of this system, is largely unknown (Hall & Collis 1995). Integrons can be located in the chromosome, in transposons, which have the ability to copy them themselves to other DNA molecules, or on plasmids. The emergence of resistant bacteria normally happens because of selection for a resistant clone of bacteria. Several mechanisms, however, exists by which the resistance genes can be transferred from one bacteria to another. Conjugation, mediated by plasmids or conjugative transposons, is currently the most well established of these mechanisms. Still, however, the selection pressure created by the use of antibiotics determines whether bacteria that have newly acquired a resistance gene expand to dominate in the population or remains a blink in history.199910783713
4116140.9980Does the use of antibiotics in food animals pose a risk to human health? A critical review of published data. The use of antibiotics in food animals selects for bacteria resistant to antibiotics used in humans, and these might spread via the food to humans and cause human infection, hence the banning of growth-promoters. The actual danger seems small, and there might be disadvantages to human and to animal health. The low dosages used for growth promotion are an unquantified hazard. Although some antibiotics are used both in animals and humans, most of the resistance problem in humans has arisen from human use. Resistance can be selected in food animals, and resistant bacteria can contaminate animal-derived food, but adequate cooking destroys them. How often they colonize the human gut, and transfer resistance genes is not known. In zoonotic salmonellosis, resistance may arise in animals or humans, but human cross-infection is common. The case of campylobacter infection is less clear. The normal human faecal flora can contain resistant enterococci, but indistinguishable strains in animals and man are uncommon, possibly because most animal enterococci do not establish themselves in the human intestine. There is no correlation between the carriage of resistant enterococci of possible animal origin and human infection with resistant strains. Commensal Escherichia coli also exhibits host-animal preferences. Anti-Gram-positive growth promoters would be expected to have little effect on most Gram-negative organisms. Even if resistant pathogens do reach man, the clinical consequences of resistance may be small. The application of the 'precautionary principle' is a non-scientific approach that assumes that risk assessments will be carried out.200414657094
3819150.9980Enhancement of bacterial competitive fitness by apramycin resistance plasmids from non-pathogenic Escherichia coli. The study of antibiotic resistance has in the past focused on organisms that are pathogenic to humans or animals. However, the development of resistance in commensal organisms is of concern because of possible transfer of resistance genes to zoonotic pathogens. Conjugative plasmids are genetic elements capable of such transfer and are traditionally thought to engender a fitness burden on host bacteria. In this study, conjugative apramycin resistance plasmids isolated from newborn calves were characterized. Calves were raised on a farm that had not used apramycin or related aminoglycoside antibiotics for at least 20 months prior to sampling. Of three apramycin resistance plasmids, one was capable of transfer at very high rates and two were found to confer fitness advantages on new Escherichia coli hosts. This is the first identification of natural plasmids isolated from commensal organisms that are able to confer a fitness advantage on a new host. This work indicates that reservoirs of antibiotic resistance genes in commensal organisms might not decrease if antibiotic usage is halted.200617148431
4604160.9979Dissemination of the strA-strB streptomycin-resistance genes among commensal and pathogenic bacteria from humans, animals, and plants. Gene transfer within bacterial communities has been recognized as a major contributor in the recent evolution of antibiotic resistance on a global scale. The linked strA-strB genes, which encode streptomycin-inactivating enzymes, are distributed worldwide and confer streptomycin resistance in at least 17 genera of gram-negative bacteria. Nucleotide sequence analyses suggest that strA-strB have been recently disseminated. In bacterial isolates from humans and animals, strA-strB are often linked with the suIII sulfonamide-resistance gene and are encoded on broad-host-range nonconjugative plasmids. In bacterial isolates from plants, strA-strB are encoded on the Tn3-type transposon Tn5393 which is generally borne on conjugative plasmids. The wide distribution of the strA-strB genes in the environment suggests that gene transfer events between human, animal, and plant-associated bacteria have occurred. Although the usage of streptomycin in clinical medicine and animal husbandry has diminished, the persistence of strA-strB in bacterial populations implies that factors other than direct antibiotic selection are involved in maintenance of these genes.19969147689
4044170.9979Antibiotic resistance in food-related bacteria--a result of interfering with the global web of bacterial genetics. A series of antibiotic resistance genes have been sequenced and found to be identical or nearly identical in various ecological environments. Similarly, genetic vectors responsible for assembly and mobility of antibiotic resistance genes, such as transposons, integrons and R plasmids of similar or identical type are also widespread in various niches of the environment. Many zoonotic bacteria carry antibiotic resistance genes directly from different food-producing environments to the human being. These circumstances may have a major impact on the degree for success in treating infectious diseases in man. Several recent examples demonstrate that use of antibiotics in all parts of the food production chain contributes to the increasing level of antibiotic resistance among the food-borne pathogenic bacteria. Modern industrialized food production adds extra emphasis on lowering the use of antibiotics in all parts of agriculture, husbandry and fish farming because these food products are distributed to very large numbers of humans compared to more traditional smaller scale niche production.200212222637
4610180.9979Acquired antibiotic resistance in lactic acid bacteria from food. Acquired antibiotic resistance, i.e. resistance genes located on conjugative or mobilizable plasmids and transposons can be found in species living in habitats (e.g. human and animal intestines) which are regularly challenged with antibiotics. Most data are available for enterococci and enteric lactobacilli. Raw material from animals (milk and meat) which are inadvertantly contaminated with fecal matters during production will carry antibiotic resistant lactic acid bacteria into the final fermented products such as raw milk cheeses and raw sausages. The discovered conjugative genetic elements of LAB isolated from animals and food are very similar to elements studied previously in pathogenic streptococci and enterococci, e.g. theta-type replicating plasmids of the pAMbeta1, pIP501-family, and transposons of the Tn916-type. Observed resistance genes include known genes like tetM, ermAM, cat, sat and vanA. A composite 29,871 bp resistance plasmid detected in Lactococcus lactis subsp. lactis isolated from a raw milk soft cheese contains tetS previously described in Listeria monocytogenes, cat and str from Staphylococcus aureus. Three out of five IS elements on the plasmid are almost or completely identical to IS1216 present in the vanA resistance transposon Tn1546. These data support the view that in antibiotic challenged habitats lactic acid bacteria like other bacteria participate in the communication systems which transfer resistance traits over species and genus borders. The prevalence of such bacteria with acquired resistances like enterococci is high in animals (and humans) which are regularly treated with antibiotics. The transfer of antibiotic resistant bacteria from animals into fermented and other food can be avoided if the raw substrate milk or meat is pasteurized or heat treated. Antibiotic resistance traits as selectable markers in genetic modification of lactic acid bacteria for different purposes are presently being replaced, e.g. by metabolic traits to generate food-grade vectors.199910532375
4175190.9979Resistance gene transfer in anaerobes: new insights, new problems. Investigations of antibiotic-resistance gene transfer elements in Bacteroides species have generated some new insights into how bacteria transfer resistance genes and what environmental conditions foster gene transfer. Integrated gene transfer elements, called conjugative transposons, appear to be responsible for much of the transfer of resistance genes among Bacteroides species. Conjugative transposons not only transfer themselves but also mobilize coresident plasmids and excise and mobilize unlinked integrated elements. Less is known about resistance gene transfer elements of the gram-positive anaerobes, but there are some indications that similar elements may be found in them as well. An unusual feature of the Bacteroides conjugative transposons is that transfer of many of them is stimulated considerably by low concentrations of antibiotics. Thus, antibiotics not only select for resistant strains but also can stimulate transfer of the resistance gene in the first place. This finding raises questions about whether use of low-dose tetracycline therapy may have a greater effect on the resident microflora than had been previously thought. Finally, investigations of resistance genes in Bacteroides species and other genera of bacteria have begun to provide evidence that the resident microflora of the human body does indeed act as a reservoir for resistance genes, which may be acquired from and passed on the transient colonizers of the site.19968953105