The tetracycline resistance gene tet(M) exhibits mosaic structure. - Related Documents




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452601.0000The 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
446510.9999Genetic analyses of sulfonamide resistance and its dissemination in gram-negative bacteria illustrate new aspects of R plasmid evolution. In contrast to what has been observed for many other antibiotic resistance mechanisms, there are only two known genes encoding plasmid-borne sulfonamide resistance. Both genes, sulI and sulII, encode a drug-resistant dihydropteroate synthase enzyme. In members of the family Enterobacteriaceae isolated from several worldwide sources, plasmid-mediated resistance to sulfonamides could be identified by colony hybridization as being encoded by sulI, sulII, or both. The sulI gene was in all cases found to be located in the newly defined, mobile genetic element, recently named an integron, which has been shown to contain a site-specific recombination system for the integration of various antibiotic resistance genes. The sulII gene was almost exclusively found as part of a variable resistance region on small, nonconjugative plasmids. Colony hybridization to an intragenic probe, restriction enzyme digestion, and nucleotide sequence analysis of small plasmids indicated that the sulII gene and contiguous sequences represent an independently occurring region disseminated in the bacterial population. The sulII resistance region was bordered by direct repeats, which in some plasmids were totally or partially deleted. The prevalence of sulI and sulII could thus be accounted for by their stable integration in transposons and in plasmids that are widely disseminated among gram-negative bacteria.19911952855
450120.9999A Bacteroides tetracycline resistance gene represents a new class of ribosome protection tetracycline resistance. The ribosome protection type of tetracycline resistance (Tcr) has been found in a variety of bacterial species, but the only two classes described previously, Tet(M) and Tet(O), shared a high degree of amino acid sequence identity (greater than 75%). Thus, it appeared that this type of resistance emerged recently in evolution and spread among different species of bacteria by horizontal transmission. We obtained the DNA sequence of a Tcr gene from Bacteroides, a genus of gram-negative, obligately anaerobic bacteria that is phylogenetically distant from the diverse species in which tet(M) and tet(O) have been found. The Bacteroides Tcr gene defines a new class of ribosome protection resistance genes, Tet(Q), and has a deduced amino acid sequence that was only 40% identical to Tet(M) or Tet(O). Like tet(M) and tet(O), tet(Q) appears to have spread by horizontal transmission, but only within the Bacteroides group.19921339256
452330.9999Mosaic structure of a multiple-drug-resistant, conjugative plasmid from Campylobacter jejuni. Partial sequence analysis of a tet(O) plasmid from a multiple-drug-resistant clinical isolate of Campylobacter jejuni revealed 10 genes or pseudogenes encoding different aminoglycoside inactivating enzymes, transposase-like genes, and multiple unknown genes from a variety of pathogenic and commensal bacteria. The plasmid could be mobilized by a P incompatibility group plasmid into Escherichia coli, where it apparently integrated into the chromosome and expressed high-level resistance to multiple aminoglycoside antibiotics. This work provides new information about both the nature of drug resistance in C. jejuni and the ability of C. jejuni to exchange genes with other bacterial species.200515917546
452840.9998Study on the excision and integration mediated by class 1 integron in Streptococcus pneumoniae. As a novel antibiotic resistance mobile element, integron was recognized as a primary source of antibiotic genes among Gram-positive organisms for its excision and integration of exogenous genes. In this study, Streptococcus pneumoniae was subjected to investigate the excision and integration of class 1 integron with eight different plasmids. As the results indicated, excision in both att site and gene cassettes were successfully observed, which was further confirmed by integration assays and PCR amplification. The observation of class 1 integron mediated excision and integration of various exogenous antibiotics resistance genes may raise the attention of integrons as novel antibiotic resistance determinant in Gram-positive bacteria, especially in Streptococcus.201728923604
452750.9998Study on the excision and integration mediated by class 1 integron in Enterococcus faecalis. Recognized as a mobile genetic element, integron is correlated to the excision and integration of exogenous genes, especially bacterial resistance genes. However, most of the investigations focused on Gram-positive bacteria with few exceptions. In this study, Enterococcus faecalis was selected to investigate the excision and integration of class 1 integron. A total of eight plasmids were subjected to establish the transformants for excision and integration test. As results showed, positive excision assay was observed, which had been confirmed by the further integration assays and PCR amplification. The observation of class 1 integron mediated excision and integration of various exogenous antibiotics resistance genes should raise the attention of integrons as novel antibiotic resistance determinant in Gram-positive bacteria, especially in Enterococcus.201728390978
446660.9998Antibiotic resistance in gram-negative bacteria: the role of gene cassettes and integrons. Resistance of gram-negative organisms to antibiotics such as beta-lactams, aminoglycosides, trimethoprim and chloramphenicol is caused by many different acquired genes, and a substantial proportion of these are part of small mobile elements known as gene cassettes. A gene cassette consists of the gene and a downstream sequence, known as a 59-base element (59-be), that acts as a specific recombination site. Gene cassettes can move into or out of a specific receptor site (attl site) in a companion element called an integron, and integration or excision of the cassettes is catalysed by a site-specific recombinase (Intl) that is encoded by the integron. At present count there are 40 different cassette-associated resistance genes and three distinct classes of integron, each encoding a distinct Intl integrase. The same cassettes are found in all three classes of integron, indicating that cassettes can move freely between different integrons. Integrons belonging to class I often contain a further antibiotic resistance gene, sull, conferring resistance to sulphonamides. The sull gene is found in a conserved region (3'-CS) that is not present in all members of this class. Class I integrons of the sull type are most prevalent in clinical isolates and have been found in many different organisms. Even though most of them are defective transposon derivatives, having lost at least one of the transposition genes, they are none the less translocatable and consequently found in many different locations. The transposon Tn7 is the best known representative of class 2 integrons, and Tn7 and relatives are also found in many different species.199816904397
452470.9998Functional genomics in Campylobacter coli identified a novel streptomycin resistance gene located in a hypervariable genomic region. Numerous aminoglycoside resistance genes have been reported in Campylobacter spp. often resembling those from Gram-positive bacterial species and located in transferable genetic elements with other resistance genes. We discovered a new streptomycin (STR) resistance gene in Campylobactercoli showing 27-34 % amino acid identity to aminoglycoside 6-nucleotidyl-transferases described previously in Campylobacter. STR resistance was verified by gene expression and insertional inactivation. This ant-like gene differs from the previously described aminoglycoside resistance genes in Campylobacter spp. in several aspects. It does not appear to originate from Gram-positive bacteria and is located in a region corresponding to a previously described hypervariable region 14 of C. jejuni with no other known resistance genes detected in close proximity. Finally, it does not belong to a multiple drug resistance plasmid or transposon. This novel ant-like gene appears widely spread among C. coli as it is found in strains originating both from Europe and the United States and from several, apparently unrelated, hosts and environmental sources. The closest homologue (60 % amino acid identity) was found in certain C. jejuni and C. coli strains in a similar genomic location, but an association with STR resistance was not detected. Based on the findings presented here, we hypothesize that Campylobacter ant-like gene A has originated from a common ancestral proto-resistance element in Campylobacter spp., possibly encoding a protein with a different function. In conclusion, whole genome sequencing allowed us to fill in a knowledge gap concerning STR resistance in C. coli by revealing a novel STR resistance gene possibly inherent to Campylobacter.201627154456
446480.9998Class 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
450090.9998Mosaic tetracycline resistance genes encoding ribosomal protection proteins. First reported in 2003, mosaic tetracycline resistance genes are a subgroup of the genes encoding ribosomal protection proteins (RPPs). They are formed when two or more RPP-encoding genes recombine resulting in a functional chimera. To date, the majority of mosaic genes are derived from sections of three RPP genes, tet(O), tet(W) and tet(32), with others comprising tet(M) and tet(S). In this first review of mosaic genes, we report on their structure, diversity and prevalence, and suggest that these genes may be responsible for an under-reported contribution to tetracycline resistance in bacteria.201627494928
4467100.9998PCR mapping of integrons reveals several novel combinations of resistance genes. The integron is a new type of mobile element which has evolved by a site-specific recombinational mechanism. Integrons consist of two conserved segments of DNA separated by a variable region containing one or more genes integrated as cassettes. Oligonucleotide probes specific for the conserved segments have revealed that integrons are widespread in recently isolated clinical bacteria. Also, by using oligonucleotide probes for several antibiotic resistance genes, we have found novel combinations of resistance genes in these strains. By using PCR, we have determined the content and order of the resistance genes inserted between the conserved segments in the integrons of these clinical isolates. PCR mapping of integrons can be a useful epidemiological tool to study the evolution of multiresistance plasmids and transposons and dissemination of antibiotic resistance genes.19957695304
4463110.9998Composite mobile genetic elements disseminating macrolide resistance in Streptococcus pneumoniae. Macrolide resistance in Streptococcus pneumoniae emerged in the U.S. and globally during the early 1990's. The RNA methylase encoded by erm(B) and the macrolide efflux genes mef(E) and mel were identified as the resistance determining factors. These genes are disseminated in the pneumococcus on mobile, often chimeric elements consisting of multiple smaller elements. To better understand the variety of elements encoding macrolide resistance and how they have evolved in the pre- and post-conjugate vaccine eras, the genomes of 121 invasive and ten carriage isolates from Atlanta from 1994 to 2011 were analyzed for mobile elements involved in the dissemination of macrolide resistance. The isolates were selected to provide broad coverage of the genetic variability of antibiotic resistant pneumococci and included 100 invasive isolates resistant to macrolides. Tn916-like elements carrying mef(E) and mel on the Macrolide Genetic Assembly (Mega) and erm(B) on the erm(B) element and Tn917 were integrated into the pneumococcal chromosome backbone and into larger Tn5253-like composite elements. The results reported here include identification of novel insertion sites for Mega and characterization of the insertion sites of Tn916-like elements in the pneumococcal chromosome and in larger composite elements. The data indicate that integration of elements by conjugation was infrequent compared to recombination. Thus, it appears that conjugative mobile elements allow the pneumococcus to acquire DNA from distantly related bacteria, but once integrated into a pneumococcal genome, transformation and recombination is the primary mechanism for transmission of novel DNA throughout the pneumococcal population.201525709602
4499120.9998Organization of two sulfonamide resistance genes on plasmids of gram-negative bacteria. The organization of two widely distributed sulfonamide resistance genes has been studied. The type I gene was linked to other resistance genes, like streptomycin resistance in R100 and trimethoprim resistance in R388 and other recently isolated plasmids from Sri Lanka. In R388, the sulfonamide resistance gene was transcribed from a promoter of its own, but in all other studied plasmids the linked genes were transcribed from a common promoter. This was especially established with a clone derived from plasmid R6-5, in which transposon mutagenesis showed that expression of sulfonamide resistance was completely dependent on the linked streptomycin resistance gene. The type II sulfonamide resistance gene was independently transcribed and found on two kinds of small resistance plasmids and also on large plasmids isolated from clinical material.19873032095
4498130.9998A naturally occurring gene amplification leading to sulfonamide and trimethoprim resistance in Streptococcus agalactiae. Gene amplifications have been detected as a transitory phenomenon in bacterial cultures. They are predicted to contribute to rapid adaptation by simultaneously increasing the expression of genes clustered on the chromosome. However, genome amplifications have rarely been described in natural isolates. Through DNA array analysis, we have identified two Streptococcus agalactiae strains carrying tandem genome amplifications: a fourfold amplification of 13.5 kb and a duplication of 92 kb. Both amplifications were located close to the terminus of replication and originated independently from any long repeated sequence. They probably arose in the human host and showed different stabilities, the 13.5-kb amplification being lost at a frequency of 0.003 per generation and the 92-kb tandem duplication at a frequency of 0.035 per generation. The 13.5-kb tandem amplification carried the five genes required for dihydrofolate biosynthesis and led to both trimethoprim (TMP) and sulfonamide (SU) resistance. Resistance to SU probably resulted from the increased synthesis of dihydropteroate synthase, the target of this antibiotic, whereas the amplification of the whole pathway was responsible for TMP resistance. This revealed a new mechanism of resistance to TMP involving an increased dihydrofolate biosynthesis. This is, to our knowledge, the first reported case of naturally occurring antibiotic resistance resulting from genome amplification in bacteria. The low stability of DNA segment amplifications suggests that their role in antibiotic resistance might have been underestimated.200818024520
3597140.9998Evidence for extensive resistance gene transfer among Bacteroides spp. and among Bacteroides and other genera in the human colon. Transfer of antibiotic resistance genes by conjugation is thought to play an important role in the spread of resistance. Yet virtually no information is available about the extent to which such horizontal transfers occur in natural settings. In this paper, we show that conjugal gene transfer has made a major contribution to increased antibiotic resistance in Bacteroides species, a numerically predominant group of human colonic bacteria. Over the past 3 decades, carriage of the tetracycline resistance gene, tetQ, has increased from about 30% to more than 80% of strains. Alleles of tetQ in different Bacteroides species, with one exception, were 96 to 100% identical at the DNA sequence level, as expected if horizontal gene transfer was responsible for their spread. Southern blot analyses showed further that transfer of tetQ was mediated by a conjugative transposon (CTn) of the CTnDOT type. Carriage of two erythromycin resistance genes, ermF and ermG, rose from <2 to 23% and accounted for about 70% of the total erythromycin resistances observed. Carriage of tetQ and the erm genes was the same in isolates taken from healthy people with no recent history of antibiotic use as in isolates obtained from patients with Bacteroides infections. This finding indicates that resistance transfer is occurring in the community and not just in clinical environments. The high percentage of strains that are carrying these resistance genes in people who are not taking antibiotics is consistent with the hypothesis that once acquired, these resistance genes are stably maintained in the absence of antibiotic selection. Six recently isolated strains carried ermB genes. Two were identical to erm(B)-P from Clostridium perfringens, and the other four had only one to three mismatches. The nine strains with ermG genes had DNA sequences that were more than 99% identical to the ermG of Bacillus sphaericus. Evidently, there is a genetic conduit open between gram-positive bacteria, including bacteria that only pass through the human colon, and the gram-negative Bacteroides species. Our results support the hypothesis that extensive gene transfer occurs among bacteria in the human colon, both within the genus Bacteroides and among Bacteroides species and gram-positive bacteria.200111157217
4477150.9998Mechanisms of antibiotic resistance and their dissemination of resistance genes in the hospital environment. The dissemination of resistance determinants among bacterial populations depends on ecological and epidemiological properties as well as additional factors: 1) the mechanism of resistance or its specificity toward a certain drug, and 2) the genetic basis in relation to the mobility of the genetic material and its survival in bacteria. From two resistance mechanisms directed toward old-fashioned drugs, namely sulfonamides (Su) and streptomycin (Sm), we can deduce that a resistance mechanism is encoded by a special sort of genetic material. Thus the linked SmSu resistance mediated by a sulfonamide-resistant dihydropteroatsynthetase II and the aminoglycoside phosphotransferase APH-(3") is always located on very small pBP1-like plasmids. Such plasmids survive without selective pressure of drugs in Enterobacteriaceae in the bowel flora of humans and animals. Both resistance determinants can be mediated by a transposon which codes for the production of a dihydropteroatsynthetase I in connection with an aminoglycoside adenylyltransferase AAD-(3"). These two mechanisms are genetically linked as well. The basic structure is a transposon designated Tn2411, which belongs to a whole family of transposons, all including the basic structure; however, their genetic exchange and substitution leads to structures coding for many different enzymatic characters: ANT-(2") (Gentamicin resistance), CAT (Chloramphenicol resistance), AAC-(6') (resistance to all modern aminoglycosides), TEM-1, OXA-1, OXA-2, or PSE (beta-lactam resistance). Resistance to the modern beta-lactamase-stable antibiotics is mediated by mutation in the regulatory genes of chromosomally-determined beta-lactamases. A spread of these resistance mechanisms can be avoided as long as the responsible genes are not located on sufficient structures like small plasmids or efficient transposons.19836558024
4660160.9998Recovery of new integron classes from environmental DNA. Integrons are genetic elements known for their role in the acquisition and expression of genes conferring antibiotic resistance. Such acquisition is mediated by an integron-encoded integrase, which captures genes that are part of gene cassettes. To test whether integrons occur in environments with no known history of antibiotic exposure, PCR primers were designed to conserved regions of the integrase gene and the gene cassette recombination site. Amplicons generated from four environmental DNA samples contained features typical of the integrons found in antibiotic-resistant and pathogenic bacteria. The sequence diversity of the integrase genes in these clones was sufficient to classify them within three new classes of integron. Since they are derived from environments not associated with antibiotic use, integrons appear to be more prevalent in bacteria than previously observed.200111166996
4497170.9998Detection and expression analysis of tet(B) in Streptococcus oralis. Tetracycline resistance can be achieved through tet genes, which code for efflux pumps, ribosomal protection proteins and inactivation enzymes. Some of these genes have only been described in either Gram-positive or Gram-negative bacteria. This is the case of tet(B), which codes for an efflux pump and, so far, had only been found in Gram-negative bacteria. In this study, tet(B) was detected in two clinical Streptococcus oralis strains isolated from the gingival sulci of two subjects. In both cases, the gene was completely sequenced, yielding 100% shared identity and coverage with other previously published sequences of tet(B). Moreover, we studied the expression of tet(B) using RT-qPCR in the isolates grown with and without tetracycline, detecting constitutive expression in only one of the isolates, with no signs of expression in the other one. This is the first time that the presence and expression of the tet(B) gene has been confirmed in Gram-positive bacteria, which highlights the potential of the genus Streptococcus to become a reservoir and a disseminator of antibiotic resistance genes in an environment so prone to horizontal gene transfer as is the oral biofilm.201931448060
9974180.9998Role of Plasmids in Co-Selection of Antimicrobial Resistances Among Escherichia coli Isolated from Pigs. Co-selection is thought to occur when resistance genes are located on the same mobile genetic element. However, this mechanism is currently poorly understood. In this study, complete circular plasmids from swine-derived Escherichia coli were sequenced with short and long reads to confirm that resistance genes involved in co-resistance were co-transferred by the same plasmid. Conjugative transfer tests were performed, and multiple resistance genes were transmitted. The genes possessed by the donor, transconjugant, and plasmid of the donor were highly similar. In addition, the sequences of the plasmid of the donor and the plasmid of the transconjugant were almost identical. Resistance genes associated with statistically significant combinations of antimicrobial use and resistance were co-transmitted by the same plasmid. These results suggest that resistance genes may be involved in co-selection by their transfer between bacteria on the same plasmid.202337540099
9889190.9998Evolution and dissemination of L and M plasmid lineages carrying antibiotic resistance genes in diverse Gram-negative bacteria. Conjugative, broad host-range plasmids of the L/M complex have been associated with antibiotic resistance since the 1970s. They are found in Gram-negative bacterial genera that cause human infections and persist in hospital environments. It is crucial that these plasmids are typed accurately so that their clinical and global dissemination can be traced in epidemiological studies. The L/M complex has previously been divided into L, M1 and M2 subtypes. However, those types do not encompass all diversity seen in the group. Here, we have examined 148 complete L/M plasmid sequences in order to understand the diversity of the complex and trace the evolution of distinct lineages. The backbone sequence of each plasmid was determined by removing translocatable genetic elements and reversing their effects in silico. The sequence identities of replication regions and complete backbones were then considered for typing. This supported the distinction of L and M plasmids and revealed that there are five L and eight M types, where each type is comprised of further sub-lineages that are distinguished by variation in their backbone and translocatable element content. Regions containing antibiotic resistance genes in L and M sub-lineages have often formed by initial rare insertion events, followed by insertion of other translocatable elements within the inceptive element. As such, islands evolve in situ to contain genes conferring resistance to multiple antibiotics. In some cases, different plasmid sub-lineages have acquired the same or related resistance genes independently. This highlights the importance of these plasmids in acting as vehicles for the dissemination of emerging resistance genes. Materials are provided here for typing plasmids of the L/M complex from complete sequences or draft genomes. This should enable rapid identification of novel types and facilitate tracking the evolution of existing lineages.202132781088