Mobile genetic elements beyond the VanB-resistance dissemination among hospital-associated enterococci and other Gram-positive bacteria. - Related Documents




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995401.0000Mobile genetic elements beyond the VanB-resistance dissemination among hospital-associated enterococci and other Gram-positive bacteria. An increasing resistance to vancomycin among clinically relevant enterococci, such as Enterococcus faecalis and Enterococcus faecium is a cause of a great concern, as it seriously limits treatment options. The vanB operon is one of most common determinants of this type of resistance. Genes constituting the operon are located in conjugative transposons, such as Tn1549-type transposons or, more rarely, in ICEEfaV583-type structures. Such elements show differences in structure and size, and reside in various sites of bacterial chromosome or, in the case of Tn1549-type transposons, are also occasionally associated with plasmids of divergent replicon types. While conjugative transposition contributes to the acquisition of Tn1549-type transposons from anaerobic gut commensals by enterococci, chromosomal recombination and conjugal transfer of plasmids appear to represent main mechanisms responsible for horizontal dissemination of vanB determinants among hospital E. faecalis and E. faecium. This review focuses on diversity of genetic elements harbouring vanB determinants in hospital-associated strains of E. faecium and E. faecalis, the mechanisms beyond vanB spread in populations of these bacteria, and provides an overview of the vanB-MGE distribution among other enterococci and Gram-positive bacteria as potential reservoirs of vanB genes.202133472048
994910.9999Presence and dissemination of the multiresistance gene cfr in Gram-positive and Gram-negative bacteria. The emergence of the multiresistance gene cfr in staphylococci is of global concern. In addition to conferring resistance to phenicols, lincosamides, pleuromutilins, streptogramin A antibiotics and selected 16-membered macrolides, the cfr gene also confers resistance to the oxazolidinone linezolid. Linezolid is a last-resort antimicrobial agent for the treatment of serious infections in humans caused by resistant Gram-positive bacteria. The cfr gene is often located on plasmids and several cfr-carrying plasmids have been described, which differ in their structure, their size and the presence of additional resistance genes. These plasmids are important vehicles that promote the spread of the cfr gene not only among bacteria of the same species, but also among those of different species and genera. Moreover, the cfr gene has been identified in close proximity to different insertion sequences, which most probably also play an important role in its dissemination. This review summarizes current knowledge on the genetic environment of the multiresistance gene cfr with particular reference to mobile genetic elements and co-located resistance genes that may support its emergence.201323543608
459420.9998Linezolid resistance genes and genetic elements enhancing their dissemination in enterococci and streptococci. Linezolid is considered a last resort drug in treatment of severe infections caused by Gram-positive pathogens, resistant to other antibiotics, such as vancomycin-resistant enterococci (VRE), methicillin-resistant staphylococci and multidrug resistant pneumococci. Although the vast majority of Gram-positive pathogenic bacteria remain susceptible to linezolid, resistant isolates of enterococci, staphylococci and streptococci have been reported worldwide. In these bacteria, apart from mutations, affecting mostly the 23S rRNA genes, acquisition of such genes as cfr, cfr(B), optrA and poxtA, often associated with mobile genetic elements (MGE), plays an important role for resistance. The purpose of this paper is to provide an overview on diversity and epidemiology of MGE carrying linezolid-resistance genes among clinically-relevant Gram-positive pathogens such as enterococci and streptococci.201830253132
414430.9998The 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
995340.9998Tn916-like genetic elements: a diverse group of modular mobile elements conferring antibiotic resistance. Antibiotic-resistant Gram-positive bacteria are responsible for morbidity and mortality in healthcare environments. Enterococcus faecium, Enterococcus faecalis, Staphylococcus aureus and Streptococcus pneumoniae can all exhibit clinically relevant multidrug resistance phenotypes due to acquired resistance genes on mobile genetic elements. It is possible that clinically relevant multidrug-resistant Clostridium difficile strains will appear in the future, as the organism is adept at acquiring mobile genetic elements (plasmids and transposons). Conjugative transposons of the Tn916/Tn1545 family, which carry major antibiotic resistance determinants, are transmissible between these different bacteria by a conjugative mechanism during which the elements are excised by a staggered cut from donor cells, converted to a circular form, transferred by cell-cell contact and inserted into recipient cells by a site-specific recombinase. The ability of these conjugative transposons to acquire additional, clinically relevant antibiotic resistance genes importantly contributes to the emergence of multidrug resistance.201121658082
459350.9998Origin, evolution and dissemination of antibiotic resistance genes. Comparison of resistance genes from different sources support the hypothesis that the antibiotic-producing microorganisms are the source of resistant determinants present in clinical isolates. There is also evidence that Gram-positive cocci (staphylococci and streptococci) can serve as a reservoir of resistance genes for Gram-negative bacteria.19872856426
446460.9998Class 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
413270.9998Mobilization 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
447280.9998Conjugative 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
479990.9998Glycopeptide-resistant enterococci: a decade of experience. Since their first description in 1988, glycopeptide-resistant enterococci (GRE) have emerged as a significant cause of nosocomial infections and colonisations, particularly in Europe and the USA. Two major genetically distinct forms of acquired resistance, designated VanA and VanB, are recognised, although intrinsic resistance occurs in some enterococcal species (VanC) and a third form of acquired resistance (VanD) has been reported recently. The biochemical basis of each resistance mechanism is similar; the resistant enterococci produce modified peptidoglycan precursors that show decreased binding affinity for glycopeptide antibiotics. Although VanA resistance is detected readily in the clinical laboratory, the variable levels of vancomycin resistance associated with the other phenotypes makes detection less reliable. Under-reporting of VanB resistance as a result of a lower detection rate may account, in part, for the difference in the numbers of enterococci displaying VanA and VanB resistance referred to the PHLS Laboratory of Hospital Infection. Since 1987, GRE have been referred from >1100 patients in almost 100 hospitals, but 88% of these isolates displayed the VanA phenotype. It is possible that, in addition to the problems of detection, there may be a real difference in the prevalence of VanA and VanB resistance reflecting different epidemiologies. Our present understanding of the genetic and biochemical basis of these acquired forms of glycopeptide resistance has been gained mainly in the last 5 years. However, these relatively new enterococcal resistances appear still to be evolving; there have now been reports of transferable VanB resistance associated with either large chromosomally borne transposons or plasmids, genetic linkage of glycopeptide resistance and genes conferring high-level resistance to aminoglycoside antibiotics, epidemic strains of glycopeptide-resistant Enterococcus faecium isolated from multiple patients in numerous hospitals, and of glycopeptide dependence (mutant enterococci that actually require these agents for growth). The gene clusters responsible for VanA and VanB resistance are located on transposable elements, and both transposition and plasmid transfer have resulted in the dissemination of these resistance genes into diverse strains of several species of enterococci. Despite extensive research, knowledge of the origins of these resistances remains poor. There is little homology between the resistance genes and DNA from either intrinsically resistant gram-positive genera or from the soil bacteria that produce glycopeptides, which argues against direct transfer to enterococci from these sources. However, recent data suggest a more distant, evolutionary relationship with genes found in glycopeptide-producing bacteria. In Europe, VanA resistance occurs in enterococci isolated in the community, from sewage, animal faeces and raw meat. This reservoir suggests that VanA may not have evolved in hospitals, and its existence has been attributed, controversially, to use of the glycopeptide avoparcin as a growth promoter, especially in pigs and poultry. However, as avoparcin has never been licensed for use in the USA and, to date, VanB resistance has not been confirmed in non-human enterococci, it is clear that the epidemiology of acquired glycopeptide resistance in enterococci is complex, with many factors contributing to its evolution and global dissemination.19989788808
4595100.9998Transfer of mupirocin resistance from Staphylococcus haemolyticus clinical strains to Staphylococcus aureus through conjugative and mobilizable plasmids. Coagulase-negative staphylococci are thought to act as reservoirs of antibiotic resistance genes that can be transferred to Staphylococcus aureus, thus hindering the combat of this bacterium. In this work, we analyzed the presence of plasmids conferring resistance to the antibiotic mupirocin-widely used to treat and prevent S. aureus infections in hospital environments-in nosocomial S. haemolyticus strains. About 12% of the 75 strains tested were resistant to mupirocin, and this phenotype was correlated with the presence of plasmids. These plasmids were shown to be diverse, being either conjugative or mobilizable, and capable of transferring mupirocin resistance to S. aureus Our findings reinforce that S. haemolyticus, historically and mistakenly considered as a less important pathogen, is a reservoir of resistance genes which can be transferred to other bacteria, such as S. aureus, emphasizing the necessity of more effective strategies to detect and combat this emergent opportunistic pathogen.201627190144
9907110.9998Mobile Genetic Elements Associated with Antimicrobial Resistance. Strains of bacteria resistant to antibiotics, particularly those that are multiresistant, are an increasing major health care problem around the world. It is now abundantly clear that both Gram-negative and Gram-positive bacteria are able to meet the evolutionary challenge of combating antimicrobial chemotherapy, often by acquiring preexisting resistance determinants from the bacterial gene pool. This is achieved through the concerted activities of mobile genetic elements able to move within or between DNA molecules, which include insertion sequences, transposons, and gene cassettes/integrons, and those that are able to transfer between bacterial cells, such as plasmids and integrative conjugative elements. Together these elements play a central role in facilitating horizontal genetic exchange and therefore promote the acquisition and spread of resistance genes. This review aims to outline the characteristics of the major types of mobile genetic elements involved in acquisition and spread of antibiotic resistance in both Gram-negative and Gram-positive bacteria, focusing on the so-called ESKAPEE group of organisms (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., and Escherichia coli), which have become the most problematic hospital pathogens.201830068738
4658120.9998Class 1 integrons potentially predating the association with tn402-like transposition genes are present in a sediment microbial community. Integrons are genetic elements that contribute to lateral gene transfer in bacteria as a consequence of possessing a site-specific recombination system. This system facilitates the spread of genes when they are part of mobile cassettes. Most integrons are contained within chromosomes and are confined to specific bacterial lineages. However, this is not the case for class 1 integrons, which were the first to be identified and are one of the single biggest contributors to multidrug-resistant nosocomial infections, carrying resistance to many antibiotics in diverse pathogens on a global scale. The rapid spread of class 1 integrons in the last 60 years is partly a result of their association with a specific suite of transposition functions, which has facilitated their recruitment by plasmids and other transposons. The widespread use of antibiotics has acted as a positive selection pressure for bacteria, especially pathogens, which harbor class 1 integrons and their associated antibiotic resistance genes. Here, we have isolated bacteria from soil and sediment in the absence of antibiotic selection. Class 1 integrons were recovered from four different bacterial species not known to be human pathogens or commensals. All four integrons lacked the transposition genes previously considered to be a characteristic of this class. At least two of these integrons were located on a chromosome, and none of them possessed antibiotic resistance genes. We conclude that novel class 1 integrons are present in a sediment environment in various bacteria of the beta-proteobacterial class. These data suggest that the dispersal of this class may have begun before the "antibiotic era."200616885440
4476130.9998Emerging patterns of microbial resistance. Microbial resistance arises by mutation or by inheritance. The latter is plasmid-mediated and transferable and may erode multidrug resistance to beta-lactams, aminoglycosides, tetracyclines, macrolides, lincosamides, sulfonamides, and trimethoprim. Resistance genes may transfer from one plasmid to another or from a plasmid to the chromosome or to a bacteriophage, thereby allowing rapid dissemination of resistance among bacteria. Mutational or chromosomal resistance is not readily transferable between different bacterial species or genera but is nonetheless medically important for resistance to isoniazid, methicillin, nalidixic acid, rifampin, and expanded spectrum cephalosporins.19846433290
4145140.9998Antimicrobial 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
9948150.9998Oxazolidinones: mechanisms of resistance and mobile genetic elements involved. The oxazolidinones (linezolid and tedizolid) are last-resort antimicrobial agents used for the treatment of severe infections in humans caused by MDR Gram-positive bacteria. They bind to the peptidyl transferase centre of the bacterial ribosome inhibiting protein synthesis. Even if the majority of Gram-positive bacteria remain susceptible to oxazolidinones, resistant isolates have been reported worldwide. Apart from mutations, affecting mostly the 23S rDNA genes and selected ribosomal proteins, acquisition of resistance genes (cfr and cfr-like, optrA and poxtA), often associated with mobile genetic elements [such as non-conjugative and conjugative plasmids, transposons, integrative and conjugative elements (ICEs), prophages and translocatable units], plays a critical role in oxazolidinone resistance. In this review, we briefly summarize the current knowledge on oxazolidinone resistance mechanisms and provide an overview on the diversity of the mobile genetic elements carrying oxazolidinone resistance genes in Gram-positive and Gram-negative bacteria.202235989417
4134160.9998Plasmid-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
4601170.9997CRISPR tracking reveals global spreading of antimicrobial resistance genes by Staphylococcus of canine origin. The close contact between pets and their owners is a potential source for microorganisms and genetic material exchange. Staphylococcus species considered as harmless inhabitants of animals' and humans' microbiota can act as reservoirs of antimicrobial resistance genes to more virulent species, thereby increasing their potential to resist drug therapy. This process could be inhibited by the antiplasmid immunity conferred by CRISPR systems. On the other hand, CRISPR spacer sequences can be explored as molecular clocks to track the history of genetic invasion suffered by a bacterial strain. To understand better the role of domestic dogs in human health as an antimicrobial resistance genes source, we analyzed 129 genomes of Staphylococcus strains of canine origin for the presence of CRISPR systems. Only 8% of the strains were positive for CRISPR, which is consistent with Staphylococcus role as gene reservoirs. The plasmidial origin or some spacers confirms the unsuccessful attempt of plasmid exchange in strains carrying CRISPRs. Some of these systems are within a staphylococcal cassette chromosome mec (SCCmec), sharing 98% of identity between their harboring strains. These CRISPRs' spacers reveal that this SCCmec was transferred between canine S. pseudintermedius strains, then to S. schleiferi and to Staphylococcus strains isolated from human beings. Our findings shows genetic evidence for the global spreading of pathogenic bacteria and the antimicrobial resistance genes carried by them and reinforce that, in the age of antimicrobial resistance, it is imperative that drug therapies consider the integrated nature of the relationship between pets and humans.201931030846
4526180.9997The tetracycline resistance gene tet(M) exhibits mosaic structure. Tetracycline resistance genes of the M class, tet(M), are typically found on mobile genetic elements as the conjugative transposons of gram-positive bacteria. By comparing the sequences of eight different tet(M) genes (from Enterococcus faecalis, Streptococcus pneumoniae, Staphylococcus aureus, Ureaplasma urealyticum, and Neisseria), a mosaic structure was detected which could be traced to two distinct alleles. The two alleles displayed a divergence of 8% and a different G/C content. The block structure of these genes provides evidence for the contribution of homologous recombination to the evolution and the heterogeneity of the tet(M) locus. Unlike described cases of chromosomally located mosaic loci, tet(M) is a relatively recently acquired determinant in the species examined and it would appear that mosaic structure within tet(M) has evolved after acquisition of the gene by the mobile genetic elements upon which it is located.19968812782
4488190.9997The cfr and cfr-like multiple resistance genes. The Cfr methyl transferase causes an RNA methylation of the bacterial ribosomes impeding reduced or abolished binding of many antibiotics acting at the peptidyl transferase center. It provides multi-resistance to eight classes of antibiotics, most of which are in clinical and veterinary use. The cfr gene is found in various bacteria in many geographical locations and placed on plasmids or associated with transposons. Cfr-related genes providing similar resistance have been identified in Bacillales, and now also in the pathogens Clostridium difficile and Enterococcus faecium. In addition, the presence of the cfr gene has been detected in harbours and food markets.201829378339