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Gene flow, mobile genetic elements and the recruitment of antibiotic resistance genes into Gram-negative pathogens 总被引:2,自引:0,他引:2
Antibiotics were one of the great discoveries of the 20th century. However, resistance appeared even in the earliest years of the antibiotic era. Antibiotic resistance continues to become worse, despite the ever-increasing resources devoted to combat the problem. One of the most important factors in the development of resistance to antibiotics is the remarkable ability of bacteria to share genetic resources via Lateral Gene Transfer (LGT). LGT occurs on a global scale, such that in theory, any gene in any organism anywhere in the microbial biosphere might be mobilized and spread. With sufficiently strong selection, any gene may spread to a point where it establishes a global presence. From an antibiotic resistance perspective, this means that a resistance phenotype can appear in a diverse range of infections around the globe nearly simultaneously. We discuss the forces and agents that make this LGT possible and argue that the problem of resistance can ultimately only be managed by understanding the problem from a broad ecological and evolutionary perspective. We also argue that human activities are exacerbating the problem by increasing the tempo of LGT and bacterial evolution for many traits that are important to humans. 相似文献
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Supriya Khedkar Georgy Smyshlyaev Ivica Letunic Oleksandr
M Maistrenko Luis
Pedro Coelho Askarbek Orakov Sofia K Forslund Falk Hildebrand Mechthild Luetge Thomas S B Schmidt Orsolya Barabas Peer Bork 《Nucleic acids research》2022,50(6):3155
Prokaryotic Mobile Genetic Elements (MGEs) such as transposons, integrons, phages and plasmids, play important roles in prokaryotic evolution and in the dispersal of cargo functions like antibiotic resistance. However, each of these MGE types is usually annotated and analysed individually, hampering a global understanding of phylogenetic and environmental patterns of MGE dispersal. We thus developed a computational framework that captures diverse MGE types, their cargos and MGE-mediated horizontal transfer events, using recombinases as ubiquitous MGE marker genes and pangenome information for MGE boundary estimation. Applied to ∼84k genomes with habitat annotation, we mapped 2.8 million MGE-specific recombinases to six operational MGE types, which together contain on average 13% of all the genes in a genome. Transposable elements (TEs) dominated across all taxa (∼1.7 million occurrences), outnumbering phages and phage-like elements (<0.4 million). We recorded numerous MGE-mediated horizontal transfer events across diverse phyla and habitats involving all MGE types, disentangled and quantified the extent of hitchhiking of TEs (17%) and integrons (63%) with other MGE categories, and established TEs as dominant carriers of antibiotic resistance genes. We integrated all these findings into a resource (proMGE.embl.de), which should facilitate future studies on the large mobile part of genomes and its horizontal dispersal. 相似文献
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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. 相似文献
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Pyrosequencing of antibiotic-contaminated river sediments reveals high levels of resistance and gene transfer elements 总被引:1,自引:0,他引:1
Kristiansson E Fick J Janzon A Grabic R Rutgersson C Weijdegård B Söderström H Larsson DG 《PloS one》2011,6(2):e17038
The high and sometimes inappropriate use of antibiotics has accelerated the development of antibiotic resistance, creating a major challenge for the sustainable treatment of infections world-wide. Bacterial communities often respond to antibiotic selection pressure by acquiring resistance genes, i.e. mobile genetic elements that can be shared horizontally between species. Environmental microbial communities maintain diverse collections of resistance genes, which can be mobilized into pathogenic bacteria. Recently, exceptional environmental releases of antibiotics have been documented, but the effects on the promotion of resistance genes and the potential for horizontal gene transfer have yet received limited attention. In this study, we have used culture-independent shotgun metagenomics to investigate microbial communities in river sediments exposed to waste water from the production of antibiotics in India. Our analysis identified very high levels of several classes of resistance genes as well as elements for horizontal gene transfer, including integrons, transposons and plasmids. In addition, two abundant previously uncharacterized resistance plasmids were identified. The results suggest that antibiotic contamination plays a role in the promotion of resistance genes and their mobilization from environmental microbes to other species and eventually to human pathogens. The entire life-cycle of antibiotic substances, both before, under and after usage, should therefore be considered to fully evaluate their role in the promotion of resistance. 相似文献
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《Saudi Journal of Biological Sciences》2020,27(10):2660-2668
The rise in antibiotic-resistant bacteria and contamination of water bodies is a serious issue that demands immense attention of scientific acumen. Here, we examined the pervasiveness of ESBL producing bacteria in Dal Lake and Wular Lake of Kashmir valley, India. Isolates were screened for antibiotic, heavy metal resistant elements, and their coexistence with mobile genetic elements. Out of two hundred one isolates screened, thirty-eight were found positive for ESBL production. Antibiotic profiling of ESBL positive isolates with 16 different drugs representing β-lactam or -non-β-lactam, exhibited multidrug resistance phenotype among 55% isolates. Molecular characterization revealed the occurrence of drug resistance determinants blaTEM, AmpC, qnrS, and heavy metal resistance genes (MRGs) merB, merP, merT, silE, silP, silS, and arsC. Furthermore, mobile genetic elements IntI, SulI, ISecp1, TN3, TN21 were also detected. Conjugation assay confirmed the transfer of different ARGs, HMRGs, and mobile elements in recipient Escherichia coli J53 AZR strain. Plasmid incompatibility studies showed blaTEM to be associated with Inc groups B/O, HI1, HI2, I1, N, FIA, and FIB. Co-occurrence of blaTEM, HMRGs, and mobile elements from the aquatic milieu of Kashmir, India has not been reported so far. From this study, the detection of the blaTEM gene in the bacteria Bacillus simplex and Brevibacterium frigoritolerans are found for the first time. Considering all the facts it becomes crucial to conduct studies in natural aquatic environments that could help depict the epidemiological situations in which the resistance mechanism might have clinical relevance. 相似文献
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Pseudomonas sp isolated from the Bay of Bengal (Madras coast) contained a single large plasmid (pMR1) of 146 kb. Plasmid curing was not successful with mitomycin C, sodium dodecyl sulfate, acridine orange, nalidixic acid or heat. Transfer of mercury resistance from marinePseudomonas toEscherichia coli occurred during mixed culture incubation in liquid broth at 10–4 to 10–5 ml–1. However, transconjugants lacked the plasmid pMR1 and lost their ability to resist mercury. Transformation of pMR1 intoE. coli competent cells was successful; however, the efficiency of transformation (1.49×102 Hgr transformants g–1 pMR1 DNA) was low.E. coli transformants containing the plasmid pMR1 conferred inducible resistance to mercury, arsenic and cadmium compounds similar to the parental strain, but with increased expression. The mercury resistant transformants exhibited mercury volatilization activity. A correlation existed between metal and antibiotic resistance in the plasmid pMR1. 相似文献
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抗生素在医疗、畜牧和水产养殖业的大量使用造成了环境中耐药细菌和抗性基因的日益增加,也加速了抗性基因在环境细菌间的传播扩散.本研究以环境样本直接提取的总DNA为模板,运用热不对称交错PCR (thermal asymmetric interlaced PCR, Tail-PCR)技术直接扩增抗生素抗性基因上下游序列.通过优化Tail-PCR反应程序,单循环同时扩增出tetW基因的多条侧翼序列,包括6条上游序列和9条下游序列.基于序列的生物信息学分析发现,上游包括一段反向重复序列和已知的一段tetW调节肽序列以及一个已知的插入序列,下游包括一个保守的未知序列和一个开放式阅读框架(the open reading frame,ORF)编码甲基转移酶.结果不仅发现了可能协助tetW基因传播的功能元件,也提供了一个未知侧翼序列高效和便捷的研究方法,即采用Tail-PCR技术,一组样品即能便捷获得多条侧翼序列. 相似文献
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目的 探讨一组多重耐药肺炎克雷伯菌(MDR-KPN)中获得性耐药相关基因和可移动遗传元件遗传标记的存在状况以及二者的相关性.方法 收集2008年8月至2010年5月浙江省杭州市和湖州市6所医院共47株MDR-KPN,采用聚合酶链反应(PCR)的方法分析74种获得性耐药基因和24种可移动遗传元件遗传标记,并用指标聚类分析(SPSS法)分析获得性耐药相关基因和可移动遗传元件遗传标记的相关性.结果 47株MDR-KPN共检出5种β-内酰胺类获得性耐药基因、6种氨基糖苷类获得性耐药基因、3种喹诺酮类获得性耐药基因、6种其他获得性耐药基因、1种整合子遗传标记、2种转座子遗传标记、4种插入序列遗传标记、2种接合性质粒遗传标记和1种噬菌体原标记;指标聚类分析(SPSS法)将上述阳性检出基因分成A、B两大簇.结论 指标聚类分析提示获得性耐药相关基因和可移动遗传元件密切相关;由Ⅰ类整合子( intI1)、插入序列(IS26、ISEcp1、ISKpn6)、耐药质粒(trbC)介导的TEM-1和KPC是本组菌株的特征.在肺炎克雷伯菌中做指标聚类分析为国内首次报道. 相似文献
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Mart Krupovic Kira S. Makarova Yuri I. Wolf Sofia Medvedeva David Prangishvili Patrick Forterre Eugene V. Koonin 《Environmental microbiology》2019,21(6):2056-2078
To explore the diversity of mobile genetic elements (MGE) associated with archaea of the phylum Thaumarchaeota, we exploited the property of most MGE to integrate into the genomes of their hosts. Integrated MGE (iMGE) were identified in 20 thaumarchaeal genomes amounting to 2 Mbp of mobile thaumarchaeal DNA. These iMGE group into five major classes: (i) proviruses, (ii) casposons, (iii) insertion sequence-like transposons, (iv) integrative-conjugative elements and (v) cryptic integrated elements. The majority of the iMGE belong to the latter category and might represent novel families of viruses or plasmids. The identified proviruses are related to tailed viruses of the order Caudovirales and to tailless icosahedral viruses with the double jelly-roll capsid proteins. The thaumarchaeal iMGE are all connected within a gene sharing network, highlighting pervasive gene exchange between MGE occupying the same ecological niche. The thaumarchaeal mobilome carries multiple auxiliary metabolic genes, including multicopper oxidases and ammonia monooxygenase subunit C (AmoC), and stress response genes, such as those for universal stress response proteins (UspA). Thus, iMGE might make important contributions to the fitness and adaptation of their hosts. We identified several iMGE carrying type I-B CRISPR-Cas systems and spacers matching other thaumarchaeal iMGE, suggesting antagonistic interactions between coexisting MGE and symbiotic relationships with the ir archaeal hosts. 相似文献
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Variation in gene content among strains of a bacterial species contributes to biomedically relevant differences in phenotypes such as virulence and antimicrobial resistance. Group A Streptococcus (GAS) causes a diverse array of human infections and sequelae, and exhibits a complex pathogenic behavior. To enhance our understanding of genotype-phenotype relationships in this important pathogen, we determined the complete genome sequences of four GAS strains expressing M protein serotypes (M2, M4, and 2 M12) that commonly cause noninvasive and invasive infections. These sequences were compared with eight previously determined GAS genomes and regions of variably present gene content were assessed. Consistent with the previously determined genomes, each of the new genomes is approximately 1.9 Mb in size, with approximately 10% of the gene content of each encoded on variably present exogenous genetic elements. Like the other GAS genomes, these four genomes are polylysogenic and prophage encode the majority of the variably present gene content of each. In contrast to most of the previously determined genomes, multiple exogenous integrated conjugative elements (ICEs) with characteristics of conjugative transposons and plasmids are present in these new genomes. Cumulatively, 242 new GAS metagenome genes were identified that were not present in the previously sequenced genomes. Importantly, ICEs accounted for 41% of the new GAS metagenome gene content identified in these four genomes. Two large ICEs, designated 2096-RD.2 (63 kb) and 10750-RD.2 (49 kb), have multiple genes encoding resistance to antimicrobial agents, including tetracycline and erythromycin, respectively. Also resident on these ICEs are three genes encoding inferred extracellular proteins of unknown function, including a predicted cell surface protein that is only present in the genome of the serotype M12 strain cultured from a patient with acute poststreptococcal glomerulonephritis. The data provide new information about the GAS metagenome and will assist studies of pathogenesis, antimicrobial resistance, and population genomics. 相似文献
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In order to isolate antibiotic resistance plasmids from bacterial communities found in activated sludge, derivatives of the
3-chlorobenzoate-degrading strain Pseudomonas sp. B13, tagged with the green fluorescent protein as an identification marker, were used as recipients in filter crosses.
Transconjugants were selected on agar plates containing 3-chlorobenzoate as the sole carbon source and the antibiotic tetracycline,
streptomycin or spectinomycin, and were recovered at frequencies in the range of 10−5 to 10−8 per recipient. A total of 12 distinct plasmids, designated pB1–pB12, was identified. Their sizes ranged between 41 to 69 kb
and they conferred various patterns of antibiotic resistance on their hosts. Two of the plasmids, pB10 and pB11, also mediated
resistance to inorganic mercury. Seven of the 12 plasmids were identified as broad-host-range plasmids, displaying extremely
high transfer frequencies in filter crosses, ranging from 10−1 to 10−2 per recipient cell. Ten of the 12 plasmids belonged to the IncP incompatibility group, based on replicon typing using IncP
group-specific PCR primers. DNA sequencing of PCR amplification products further revealed that eight of the 12 plasmids belonged
to the IncPβ subgroup, whereas two plasmids were identified as IncPα plasmids. Analysis of the IncP-specific PCR products
revealed considerable differences among the IncPβ plasmids at the DNA sequence level. In order to characterize the gene “load”
of the IncP plasmids, restriction fragments were cloned and their DNA sequences established. A remarkable diversity of putative
proteins encoded by these fragments was identified. Besides transposases and proteins involved in antibiotic resistance, two
putative DNA invertases belonging to the Din family, a methyltransferase of a type I restriction/modification system, a superoxide
dismutase, parts of a putative efflux system belonging to the RND family, and proteins of unknown function were identified.
Received: 11 October 1999 / Accepted: 11 January 2000 相似文献
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Molecular tools to detect the IncJ elements: a family of integrating, antibiotic resistant mobile genetic elements 总被引:1,自引:0,他引:1
McGrath BM O'Halloran JA Piterina AV Pembroke JT 《Journal of microbiological methods》2006,66(1):32-42
The IncJ group of enterobacterial mobile genetic elements, which include R391, R392, R705, R997 and pMERPH, have been shown to be site-specific integrating elements encoding variable antibiotic and heavy metal resistance genes. They insert into a specific 17-bp site located in the prfC gene, encoding peptide release factor 3, in Escherichia coli and other hosts. A key feature of known IncJ elements is the presence of a site-specific recombination module consisting of an attachment site on the element and an integrase-encoding gene of the tyrosine recombinase class, which promotes integration between the attachment site on the element and a similar site on the host chromosome. We have cloned and sequenced the integrases from a number of known IncJ elements and designed PCR primers for specific amplification of this gene. Using conserved regions of enterobacterial prfC genes upstream and downstream of the insertion site, and conserved sequences at the ends of the integrated IncJ elements, we have designed specific primers to amplify across the integrated IncJ attL and attR junction fragments. Alignment of over 30 enterobacterial prfC-like genes indicates that the primers designed to amplify attR junction would amplify IncJ element: host junctions from a wide variety of hosts. The IncJ elements have been shown to sensitise recA(+)E. coli K12 strains to UV irradiation. A simple and rapid procedure for demonstrating this effect is described. These tools should enable the rapid detection of such elements in clinical and environmental settings. 相似文献
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Margrete Solheim Mari C Brekke Lars G Snipen Rob JL Willems Ingolf F Nes Dag A Brede 《BMC microbiology》2011,11(1):3
Background
Enterococci rank among the leading causes of nosocomial infections. The failure to identify pathogen-specific genes in Enterococcus faecalis has led to a hypothesis where the virulence of different strains may be linked to strain-specific genes, and where the combined endeavor of the different gene-sets result in the ability to cause infection. Population structure studies by multilocus sequence typing have defined distinct clonal complexes (CC) of E. faecalis enriched in hospitalized patients (CC2, CC9, CC28 and CC40). 相似文献18.
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Plasmid profiles and transfer of plasmid-encoded antibiotic resistance in Lactobacillus plantarum 总被引:4,自引:0,他引:4
Plasmids were visualized in strains of Lactobacillus plantarum by use of a rapid method. Plasmids pIP501 and pAM beta 1 were transferred by conjugation from Streptococcus strains to Lactobacillus plantarum, and recipient strains were shown to act as donors in crosses to S. lactis. Attempts to transfer these plasmids between strains of L. plantarum were not successful. 相似文献
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Reservoirs of antibiotic resistance genes 总被引:1,自引:0,他引:1
A potential concern about the use of antibiotics in animal husbundary is that, as antibiotic resistant bacteria move from the farm into the human diet, they may pass antibiotic resistance genes to bacteria that normally reside in a the human intestinal tract and from there to bacteria that cause human disease (reservoir hypothesis). In this article various approaches to evaluating the risk of agricultural use of antibiotics are assessed critically. In addition, the potential benefits of applying new technology and using new insights from the field of microbial ecology are explained. 相似文献