# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 1753 | 0 | 0.9877 | Characterization of a Linezolid- and Vancomycin-Resistant Streptococcus suis Isolate That Harbors optrA and vanG Operons. Linezolid and vancomycin are among the last-resort antimicrobial agents in the treatment of multidrug-resistant Gram-positive bacterial infections. Linezolid- and vancomycin-resistant (LVR) Gram-positive bacteria may pose severe threats to public health. In this study, three optrA- and vanG-positive Streptococcus suis strains were isolated from two farms of different cities. There were only 1 and 343 single-nucleotide polymorphisms in coding region (cSNPs) of HCB4 and YSJ7 to YSJ17, respectively. Mobilome analysis revealed the presence of vanG, erm(B), tet(O/W/32/O), and aadE-apt-sat4-aphA3 cluster on an integrative and conjugative element, ICESsuYSJ17, and erm(B), aphA3, aac(6')-aph(2″), catpC(194), and optrA on a prophage, ΦSsuYSJ17-3. ICESsuYSJ17 exhibited a mosaic structure and belongs to a highly prevalent and transferable ICESa2603 family of Streptococcus species. ΦSsuYSJ17-3 shared conserved backbone to a transferable prophage Φm46.1. A novel composite transposon, IS1216E-araC-optrA-hp-catpC(194)-IS1216E, which can be circulated as translocatable unit (TU) by IS1216E, was integrated on ΦSsuYSJ17-3. Vancomycin resistance phenotype and vanG transcription assays revealed that the vanG operon was inducible. The LVR strain YSJ17 exhibited moderate virulence in a zebrafish infection model. To our knowledge, this is the first report of LVR isolate, which is mediated by acquired resistance genes optrA and vanG operons in Gram-positive bacteria. Since S. suis has been recognized as an antimicrobial resistance reservoir in the spread of resistance genes to major streptococcal pathogens, the potential risks of disseminating of optrA and vanG from S. suis to other Streptococcus spp. are worrisome and routine surveillance should be strengthened. | 2019 | 31551963 |
| 9977 | 1 | 0.9876 | IncC conjugative plasmids and SXT/R391 elements repair double-strand breaks caused by CRISPR-Cas during conjugation. Bacteria have evolved defence mechanisms against bacteriophages. Restriction-modification systems provide innate immunity by degrading invading DNAs that lack proper methylation. CRISPR-Cas systems provide adaptive immunity by sampling the genome of past invaders and cutting the DNA of closely related DNA molecules. These barriers also restrict horizontal gene transfer mediated by conjugative plasmids. IncC conjugative plasmids are important contributors to the global dissemination of multidrug resistance among pathogenic bacteria infecting animals and humans. Here, we show that IncC conjugative plasmids are highly resilient to host defence systems during entry into a new host by conjugation. Using a TnSeq strategy, we uncover a conserved operon containing five genes (vcrx089-vcrx093) that confer a novel host defence evasion (hde) phenotype. We show that vcrx089-vcrx090 promote resistance against type I restriction-modification, whereas vcrx091-vcxr093 promote CRISPR-Cas evasion by repairing double-strand DNA breaks via recombination between short sequence repeats. vcrx091, vcrx092 and vcrx093 encode a single-strand binding protein, and a single-strand annealing recombinase and double-strand exonuclease related to Redβ and λExo of bacteriophage λ, respectively. Homologous genes of the integrative and conjugative element R391 also provide CRISPR-Cas evasion. Hence, the conserved hde operon considerably broadens the host range of large families of mobile elements spreading multidrug resistance. | 2020 | 32556263 |
| 8417 | 2 | 0.9873 | The cadDX operon contributes to cadmium resistance, oxidative stress resistance, and virulence in zoonotic streptococci. Mobile genetic elements (MGEs) enable bacteria to acquire novel genes and traits. However, the functions of cargo genes within MGEs remain poorly understood. The cadmium resistance operon cadDX is present in many gram-positive bacteria. Although cadDX has been reported to be involved in metal detoxification, its regulatory mechanisms and functions in bacterial pathogenesis are poorly understood. This study revealed that cadDX contributes to cadmium resistance, oxidative stress resistance, and virulence in Streptococcus suis, an important zoonotic pathogen in pigs and humans. CadX represses cadD expression by binding to the cadDX promoter. Notably, cadX responds to H(2)O(2) stress through an additional promoter within the cadDX operon, mitigating the harmful effect of excessive cadD expression during oxidative stress. cadDX resides within an 11 K integrative and mobilizable element that can autonomously form circular structures. Moreover, cadDX is found in diverse MGEs, accounting for its widespread distribution across various bacteria, especially among pathogenic streptococci. Transferring cadDX into another zoonotic pathogen, Streptococcus agalactiae, results in similar phenotypes, including resistance to cadmium and oxidative stresses and increased virulence of S. agalactiae in mice. The new functions and regulatory mechanisms of cadDX shed light on the importance of the cadDX system in driving evolutionary adaptations and survival strategies across diverse gram-positive bacteria. | 2024 | 39334407 |
| 9945 | 3 | 0.9871 | The Ellis Island Effect: A novel mobile element in a multi-drug resistant Bacteroides fragilis clinical isolate includes a mosaic of resistance genes from Gram-positive bacteria. Objectives: Bacteroides fragilis, a Gram-negative anaerobic bacterium, is alternately a gut commensal or virulent pathogen and is an important reservoir for horizontal gene transfer (HGT) of bacterial resistance and virulence genes in the human gastrointestinal tract. We identified a unique conjugative transposon (CTn) in a multidrug resistant clinical isolate of B. fragilis (BF-HMW615); we named this element CTnHyb because it included a hybrid mosaic of foreign elements. This study reports the characterization of CTnHyb and discusses the potential impact on horizontal spread of resistance genes. Results: CTnHyb contains several efflux pump genes and several genes that confer or may confer antibiotic resistance to tetracycline, kanamycin, metronidazole and spectinomycin (truncated gene). CTnHyb also contains a mosaic of mobile elements from Gram-positive organisms. CTnHyb is easily transferred from BF-HMW615 (the original isolate) to BF638R (lab strain) and integrated into the BF638R chromosome. The "foreign" (from Gram-positive bacteria) nucleotide sequences within CTnHyb were > 99% preserved indicating that the gene acquisition from the Gram-positive bacteria was very recent. Conclusion: CTnHyb is a novel CTn residing in a multidrug resistant strain of B. fragilis. The global nature and wide phylogenetic reach of HGT means that any gene in any bacterium can potentially be mobilized. Understanding the mechanisms that drive the formation and transfer of these elements and, potentially, ways to limit the transfer are necessary to prevent a devastating spread of resistance elements. | 2014 | 25165618 |
| 9947 | 4 | 0.9871 | A novel integrative conjugative element mediates transfer of multi-drug resistance between Streptococcus suis strains of different serotypes. Streptococcus suis represents a key antibiotic resistance gene reservoir and an important pathogen for humans and animals. Resistance can be spread through horizontal gene transfer of chromosome-borne mobile genetic elements; however, the exact mechanism by which this occurs remains poorly understood. In the present study, we identified and characterized a novel 82-kb integrative conjugative element (ICE) named ICESsuCZ130302 from the virulent S. suis strain CZ130302. It carries genes that provide resistance to multiple antibiotics, such as tetracycline, doxycycline, erythromycin, lincomycin, neomycin, and kanamycin. It also contains a nisin biosynthesis gene cluster, a toxin-antitoxin system, a type IV secretion system, and an integrase and excisase system. The mobile element can be excised from the chromosome, circulized, and transferred via conjugation from serotype Chz strain CZ130302 to serotype 2 strain P1/7, where it confers resistance to the aforementioned antimicrobial agents. The full length ICE, where multiple antimicrobial resistance genes accumulated, was further identified to be naturally transferred between different serotypes strains of S. suis. This finding illustrates how such elements represent a potential means by which antimicrobial resistance is introduced to a wide range of bacteria of veterinary and medical significance. | 2019 | 30642585 |
| 3741 | 5 | 0.9871 | The fib locus in Streptococcus pneumoniae is required for peptidoglycan crosslinking and PBP-mediated beta-lactam resistance. Penicillin resistance in pneumococci is mediated by modified penicillin-binding proteins (PBPs) that have decreased affinity to beta-lactams. In high-level penicillin-resistant transformants of the laboratory strain Streptococcus pneumoniae R6 containing various combinations of low-affinity PBPs, disruption of the fib locus results in a collapse of PBP-mediated resistance. In addition, crosslinked muropeptides are highly reduced. The fib operon consists of two genes, fibA and fibB, homologous to Staphylococcus aureus femA/B which are also required for expression of methicillin resistance in this organism. FibA and FibB belong to a family of proteins of Gram-positive bacteria involved in the formation of interpeptide bridges, thus representing interesting new targets for antimicrobial compounds for this group of pathogens. | 2000 | 10867238 |
| 9830 | 6 | 0.9870 | Mechanisms of Conjugative Transfer and Type IV Secretion-Mediated Effector Transport in Gram-Positive Bacteria. Conjugative DNA transfer is the most important means to transfer antibiotic resistance genes and virulence determinants encoded by plasmids, integrative conjugative elements (ICE), and pathogenicity islands among bacteria. In gram-positive bacteria, there exist two types of conjugative systems, (i) type IV secretion system (T4SS)-dependent ones, like those encoded by the Enterococcus, Streptococcus, Staphylococcus, Bacillus, and Clostridia mobile genetic elements and (ii) T4SS-independent ones, as those found on Streptomyces plasmids. Interestingly, very recently, on the Streptococcus suis genome, the first gram-positive T4SS not only involved in conjugative DNA transfer but also in effector translocation to the host was detected. Although no T4SS core complex structure from gram-positive bacteria is available, several structures from T4SS protein key factors from Enterococcus and Clostridia plasmids have been solved. In this chapter, we summarize the current knowledge on the molecular mechanisms and structure-function relationships of the diverse conjugation machineries and emerging research needs focused on combatting infections and spread of multiple resistant gram-positive pathogens. | 2017 | 29536357 |
| 9819 | 7 | 0.9868 | Site-specific recombination and shuffling of resistance genes in transposon Tn21. Many multidrug-resistant transposons found in natural isolates of Gram-negative bacteria are close relatives of Tn21. Thus, the Tn21 subgroup of the Tn3 family of transposable elements is the most successful homogeneous group in acquiring resistance to newly introduced antibiotics. This paper summarizes the mode of acquisition of resistance genes by these elements. | 1991 | 1660178 |
| 490 | 8 | 0.9867 | Mercuric resistance genes in gram-positive oral bacteria. Mercury-resistant bacteria isolated from the oral cavities of children carried one of two types of merA gene that appear to have evolved from a common ancestor. Streptococcus oralis, Streptococcus mitis and a few other species had merA genes that were very similar to merA of Bacillus cereus strain RC607. Unlike the B. cereus RC607 merA gene, however, the streptococcal merA genes were not carried on Tn5084-like transposons. Instead, comparisons with microbial genomic sequences suggest the merA gene is located on a novel type II transposon. Coagulase-negative staphylococci and Streptococcus parasanguis had identical merA genes that represent a new merA variant. | 2004 | 15251199 |
| 9843 | 9 | 0.9867 | Conjugative transposons: an unusual and diverse set of integrated gene transfer elements. Conjugative transposons are integrated DNA elements that excise themselves to form a covalently closed circular intermediate. This circular intermediate can either reintegrate in the same cell (intracellular transposition) or transfer by conjugation to a recipient and integrate into the recipient's genome (intercellular transposition). Conjugative transposons were first found in gram-positive cocci but are now known to be present in a variety of gram-positive and gram-negative bacteria also. Conjugative transposons have a surprisingly broad host range, and they probably contribute as much as plasmids to the spread of antibiotic resistance genes in some genera of disease-causing bacteria. Resistance genes need not be carried on the conjugative transposon to be transferred. Many conjugative transposons can mobilize coresident plasmids, and the Bacteroides conjugative transposons can even excise and mobilize unlinked integrated elements. The Bacteroides conjugative transposons are also unusual in that their transfer activities are regulated by tetracycline via a complex regulatory network. | 1995 | 8531886 |
| 9856 | 10 | 0.9867 | The extended regulatory networks of SXT/R391 integrative and conjugative elements and IncA/C conjugative plasmids. Nowadays, healthcare systems are challenged by a major worldwide drug resistance crisis caused by the massive and rapid dissemination of antibiotic resistance genes and associated emergence of multidrug resistant pathogenic bacteria, in both clinical and environmental settings. Conjugation is the main driving force of gene transfer among microorganisms. This mechanism of horizontal gene transfer mediates the translocation of large DNA fragments between two bacterial cells in direct contact. Integrative and conjugative elements (ICEs) of the SXT/R391 family (SRIs) and IncA/C conjugative plasmids (ACPs) are responsible for the dissemination of a broad spectrum of antibiotic resistance genes among diverse species of Enterobacteriaceae and Vibrionaceae. The biology, diversity, prevalence and distribution of these two families of conjugative elements have been the subject of extensive studies for the past 15 years. Recently, the transcriptional regulators that govern their dissemination through the expression of ICE- or plasmid-encoded transfer genes have been described. Unrelated repressors control the activation of conjugation by preventing the expression of two related master activator complexes in both types of elements, i.e., SetCD in SXT/R391 ICEs and AcaCD in IncA/C plasmids. Finally, in addition to activating ICE- or plasmid-borne genes, these master activators have been shown to specifically activate phylogenetically unrelated mobilizable genomic islands (MGIs) that also disseminate antibiotic resistance genes and other adaptive traits among a plethora of pathogens such as Vibrio cholerae and Salmonella enterica. | 2015 | 26347724 |
| 9979 | 11 | 0.9866 | Type II and IV toxin-antitoxin systems coordinately stabilize the integrative and conjugative element of the ICESa2603 family conferring multiple drug resistance in Streptococcus suis. Integrative and conjugative elements (ICEs) play a vital role in bacterial evolution by carrying essential genes that confer adaptive functions to the host. Despite their importance, the mechanism underlying the stable inheritance of ICEs, which is necessary for the acquisition of new traits in bacteria, remains poorly understood. Here, we identified SezAT, a type II toxin-antitoxin (TA) system, and AbiE, a type IV TA system encoded within the ICESsuHN105, coordinately promote ICE stabilization and mediate multidrug resistance in Streptococcus suis. Deletion of SezAT or AbiE did not affect the strain's antibiotic susceptibility, but their duple deletion increased susceptibility, mainly mediated by the antitoxins SezA and AbiEi. Further studies have revealed that SezA and AbiEi affect the genetic stability of ICESsuHN105 by moderating the excision and extrachromosomal copy number, consequently affecting the antibiotic resistance conferred by ICE. The DNA-binding proteins AbiEi and SezA, which bind palindromic sequences in the promoter, coordinately modulate ICE excision and extracellular copy number by binding to sequences in the origin-of-transfer (oriT) and the attL sites, respectively. Furthermore, AbiEi negatively regulates the transcription of SezAT by binding directly to its promoter, optimizing the coordinate network of SezAT and AbiE in maintaining ICESsuHN105 stability. Importantly, SezAT and AbiE are widespread and conserved in ICEs harbouring diverse drug-resistance genes, and their coordinated effects in promoting ICE stability and mediating drug resistance may be broadly applicable to other ICEs. Altogether, our study uncovers the TA system's role in maintaining the genetic stability of ICE and offers potential targets for overcoming the dissemination and evolution of drug resistance. | 2024 | 38640137 |
| 4463 | 12 | 0.9866 | Composite 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. | 2015 | 25709602 |
| 454 | 13 | 0.9866 | Nucleotide sequences and comparison of two large conjugative plasmids from different Campylobacter species. Two large tetracycline resistance (TcR) plasmids have been completely sequenced, the pTet plasmid (45.2 kb) from Campylobacter jejuni strain 81-176 and a plasmid pCC31 (44.7 kb) from Campylobacter coli strain CC31 that was isolated from a human case of severe gastroenteritis in the UK. Both plasmids are mosaic in structure, having homologues of genes found in a variety of different commensal and pathogenic bacteria, but nevertheless, showed striking similarities in DNA sequence and overall gene organization. Several predicted proteins encoded by genes involved in conjugation showed highest homology to proteins found in Actinobacillus actinomycetemcomitans, a periodontal pathogen. In addition to replication- and conjugation-associated genes, both plasmids carried a tet(O) gene encoding tetracycline resistance, a 6 kb ORF encoding a putative methylase and a number of genes of unknown function. The pTet plasmid co-exists in C. jejuni strain 81-176 with a smaller, previously characterized, non-conjugative plasmid pVir that also encodes a type IV secretion system (T4SS) that may affect virulence. In contrast, the T4SS encoded by pTet and pCC31 are shown to mediate bacterial conjugation between Campylobacter. The possible origin and evolution of pCC31 and pTet is discussed. | 2004 | 15470128 |
| 9253 | 14 | 0.9866 | Horizontally transferred genetic elements and their role in pathogenesis of bacterial disease. This article reviews the roles that laterally transferred genes (LTG) play in the virulence of bacterial pathogens. The features of LTG that allow them to be recognized in bacterial genomes are described, and the mechanisms by which LTG are transferred between and within bacteria are reviewed. Genes on plasmids, integrative and conjugative elements, prophages, and pathogenicity islands are highlighted. Virulence genes that are frequently laterally transferred include genes for bacterial adherence to host cells, type 3 secretion systems, toxins, iron acquisition, and antimicrobial resistance. The specific roles of LTG in pathogenesis are illustrated by specific reference to Escherichia coli, Salmonella, pyogenic streptococci, and Clostridium perfringens. | 2014 | 24318976 |
| 9953 | 15 | 0.9866 | Tn916-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. | 2011 | 21658082 |
| 9990 | 16 | 0.9865 | Axe-Txe, a broad-spectrum proteic toxin-antitoxin system specified by a multidrug-resistant, clinical isolate of Enterococcus faecium. Enterococcal species of bacteria are now acknowledged as leading causes of bacteraemia and other serious nosocomial infections. However, surprisingly little is known about the molecular mechanisms that promote the segregational stability of antibiotic resistance and other plasmids in these bacteria. Plasmid pRUM (24 873 bp) is a multidrug resistance plasmid identified in a clinical isolate of Enterococcus faecium. A novel proteic-based toxin-antitoxin cassette identified on pRUM was demonstrated to be a functional segregational stability module in both its native host and evolutionarily diverse bacterial species. Induced expression of the toxin protein (Txe) of this system resulted in growth inhibition in Escherichia coli. The toxic effect of Txe was alleviated by co-expression of the antitoxin protein, Axe. Homologues of the axe and txe genes are present in the genomes of a diversity of Eubacteria. These homologues (yefM-yoeB) present in the E. coli chromosome function as a toxin-antitoxin mechanism, although the Axe and YefM antitoxin components demonstrate specificity for their cognate toxin proteins in vivo. Axe-Txe is one of the first functional proteic toxin-antitoxin systems to be accurately described for Gram-positive bacteria. | 2003 | 12603745 |
| 3744 | 17 | 0.9865 | Vancomycin resistance VanS/VanR two-component systems. Vancomycin is a member of the glycopeptide class of antibiotics. Vancomycin resistance (van) gene clusters are found in human pathogens such as Enterococcus faecalis, Enterococcus faecium and Staphylococcus aureus, glycopeptide-producing actinomycetes such as Amycolotopsis orientalis, Actinoplanes teichomyceticus and Streptomyces toyocaensis and the nonglycopeptide producing actinomycete Streptomyces coelicolor. Expression of the van genes is activated by the VanS/VanR two-component system in response to extracellular glycopeptide antibiotic. Two major types of inducible vancomycin resistance are found in pathogenic bacteria; VanA strains are resistant to vancomycin itself and also to the lipidated glycopeptide teicoplanin, while VanB strains are resistant to vancomycin but sensitive to teicoplanin. Here we discuss the enzymes the van genes encode, the range of different VanS/VanR two-component systems, the biochemistry of VanS/VanR, the nature of the effector ligand(s) recognised by VanS and the evolution of the van cluster. | 2008 | 18792691 |
| 8197 | 18 | 0.9865 | Specific host genes required for the killing of Klebsiella bacteria by phagocytes. The amoeba Dictyostelium discoideum shares many traits with mammalian macrophages, in particular the ability to phagocytose and kill bacteria. In response, pathogenic bacteria use conserved mechanisms to fight amoebae and mammalian phagocytes. Here we developed an assay using Dictyostelium to monitor phagocyte-bacteria interactions. Genetic analysis revealed that the virulence of Klebsiella pneumoniae measured by this test is very similar to that observed in a mouse pneumonia model. Using this assay, two new host resistance genes (PHG1 and KIL1) were identified and shown to be involved in intracellular killing of K. pneumoniae by phagocytes. Phg1 is a member of the 9TM family of proteins, and Kil1 is a sulphotransferase. The loss of PHG1 resulted in Dictyostelium susceptibility to a small subset of bacterial species including K. pneumoniae. Remarkably, Drosophila mutants deficient for PHG1 also exhibited a specific susceptibility to K. pneumoniae infections. Systematic analysis of several additional Dictyostelium mutants created a two-dimensional virulence array, where the complex interactions between host and bacteria are visualized. | 2006 | 16367873 |
| 9948 | 19 | 0.9865 | Oxazolidinones: 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. | 2022 | 35989417 |