# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 9903 | 0 | 1.0000 | Bacterial plasmid addiction systems and their implications for antibiotic drug development. Bacteria frequently carry mobile genetic elements capable of being passed to other bacterial cells. An example of this is the transfer of plasmids (small, circular DNA molecules) that often contain antibiotic resistance genes from one bacterium to another. Plasmids have evolved mechanisms to ensure their survival through generations by employing plasmids segregation and replication machinery and plasmid addiction systems. Plasmid addiction systems utilize a post-segregational killing of cells that have not received a plasmid. In this review, the types of plasmid addiction systems are described as well as their prevalence in antibiotic resistant bacteria. Lastly, the possibility of targeting these plasmid addiction systems for the treatment of antibiotic resistant bacterial infections is explored. | 2017 | 28781980 |
| 9902 | 1 | 0.9999 | Bacterial death comes full circle: targeting plasmid replication in drug-resistant bacteria. It is now common for bacterial infections to resist the preferred antibiotic treatment. In particular, hospital-acquired infections that are refractory to multiple antibiotics and ultimately result in death of the patient are prevalent. Many of the bacteria causing these infections have become resistant to antibiotics through the process of lateral gene transfer, with the newly acquired genes encoding a variety of resistance-mediating proteins. These foreign genes often enter the bacteria on plasmids, which are small, circular, extrachromosomal pieces of DNA. This plasmid-encoded resistance has been observed for virtually all classes of antibiotics and in a wide variety of Gram-positive and Gram-negative organisms; many antibiotics are no longer effective due to such plasmid-encoded resistance. The systematic removal of these resistance-mediating plasmids from the bacteria would re-sensitize bacteria to standard antibiotics. As such, plasmids offer novel targets that have heretofore been unexploited clinically. This Perspective details the role of plasmids in multi-drug resistant bacteria, the mechanisms used by plasmids to control their replication, and the potential for small molecules to disrupt plasmid replication and re-sensitize bacteria to antibiotics. An emphasis is placed on plasmid replication that is mediated by small counter-transcript RNAs, and the "plasmid addiction" systems that employ toxins and antitoxins. | 2005 | 15750634 |
| 9901 | 2 | 0.9998 | Plasmid interference for curing antibiotic resistance plasmids in vivo. Antibiotic resistance increases the likelihood of death from infection by common pathogens such as Escherichia coli and Klebsiella pneumoniae in developed and developing countries alike. Most important modern antibiotic resistance genes spread between such species on self-transmissible (conjugative) plasmids. These plasmids are traditionally grouped on the basis of replicon incompatibility (Inc), which prevents coexistence of related plasmids in the same cell. These plasmids also use post-segregational killing ('addiction') systems, which poison any bacterial cells that lose the addictive plasmid, to guarantee their own survival. This study demonstrates that plasmid incompatibilities and addiction systems can be exploited to achieve the safe and complete eradication of antibiotic resistance from bacteria in vitro and in the mouse gut. Conjugative 'interference plasmids' were constructed by specifically deleting toxin and antibiotic resistance genes from target plasmids. These interference plasmids efficiently cured the corresponding antibiotic resistant target plasmid from different Enterobacteriaceae in vitro and restored antibiotic susceptibility in vivo to all bacterial populations into which plasmid-mediated resistance had spread. This approach might allow eradication of emergent or established populations of resistance plasmids in individuals at risk of severe sepsis, enabling subsequent use of less toxic and/or more effective antibiotics than would otherwise be possible, if sepsis develops. The generalisability of this approach and its potential applications in bioremediation of animal and environmental microbiomes should now be systematically explored. | 2017 | 28245276 |
| 9310 | 3 | 0.9998 | Bacterial resistance to antibiotics. Effective antibacterial drugs have been available for nearly 50 years. After the introduction of each new such drug, whether chemically synthesized or a naturally occurring antibiotic, bacterial resistance to it has emerged. The genetic mechanisms by which bacteria have acquired resistance were quite unexpected; a new evolutionary pathways has been revealed. Although some antibiotic resistance has resulted from mutational changes in structural proteins--targets for the drugs' action--most has resulted from the acquisition of new, ready-made genes from an external source--that is, from another bacterium. Vectors of the resistance genes are plasmids--heritable DNA molecules that are transmissible between bacterial cells. Plasmids without antibiotic-resistance genes are common in all kinds of bacteria. Resistance plasmids have resulted from the insertion of new DNA sequences into previously existing plasmids. Thus, the spread of antibiotic resistance is at three levels: bacteria between people or animals; plasmids between bacteria; and transposable genes between plasmids. | 1984 | 6319093 |
| 9295 | 4 | 0.9998 | Biological activities specified by antibiotic resistance plasmids. Bacteria can display resistance to a wide spectrum of noxious agents and environmental conditions, and these properties are often mediated by genes located on extrachromosomal DNA elements called plasmids. Replication, vertical and horizontal transmission and evolution of these elements are discussed, and examples of the genes responsible for the resistance phenotypes are given. Selective forces that drive the evolution of new combinations of bacterial properties of particular importance in clinical situations are analysed. | 1986 | 3542928 |
| 4133 | 5 | 0.9998 | Importance of integrons in the diffusion of resistance. Horizontal transfer of resistance genes is a successful mechanism for the transmission and dissemination of multiple drug resistance among bacterial pathogens. The impact of horizontally transmitted genetic determinants in the evolution of resistance is particularly evident when resistance genes are physically associated in clusters and transferred en bloc to the recipient cell. Recent advances in the molecular characterisation of antibiotic resistance mechanisms have highlighted the existence of genetic structures. called integrons, involved in the acquisition of resistance genes. These DNA elements have frequently been reported in multi-drug resistant strains isolated from animals and humans, and are located either on the bacterial chromosome or on broad-host-range plasmids. The role of integrons in the development of multiple resistance relies on their unique capacity to cluster and express drug resistance genes. Moreover, the spread of resistance genes among different replicons and their exchange between plasmid and bacterial chromosome are facilitated by the integration of integrons into transposable elements. The association of a highly efficient gene capture and expression system, together with the capacity for vertical and horizontal transmission of resistance genes represents a powerful weapon used by bacteria to combat the assault of antibiotics. | 2001 | 11432416 |
| 9309 | 6 | 0.9998 | Plasmid encoded antibiotic resistance: acquisition and transfer of antibiotic resistance genes in bacteria. Bacteria have existed on Earth for three billion years or so and have become adept at protecting themselves against toxic chemicals. Antibiotics have been in clinical use for a little more than 6 decades. That antibiotic resistance is now a major clinical problem all over the world attests to the success and speed of bacterial adaptation. Mechanisms of antibiotic resistance in bacteria are varied and include target protection, target substitution, antibiotic detoxification and block of intracellular antibiotic accumulation. Acquisition of genes needed to elaborate the various mechanisms is greatly aided by a variety of promiscuous gene transfer systems, such as bacterial conjugative plasmids, transposable elements and integron systems, that move genes from one DNA system to another and from one bacterial cell to another, not necessarily one related to the gene donor. Bacterial plasmids serve as the scaffold on which are assembled arrays of antibiotic resistance genes, by transposition (transposable elements and ISCR mediated transposition) and site-specific recombination mechanisms (integron gene cassettes).The evidence suggests that antibiotic resistance genes in human bacterial pathogens originate from a multitude of bacterial sources, indicating that the genomes of all bacteria can be considered as a single global gene pool into which most, if not all, bacteria can dip for genes necessary for survival. In terms of antibiotic resistance, plasmids serve a central role, as the vehicles for resistance gene capture and their subsequent dissemination. These various aspects of bacterial resistance to antibiotics will be explored in this presentation. | 2008 | 18193080 |
| 3837 | 7 | 0.9998 | Evolutionary Paths That Expand Plasmid Host-Range: Implications for Spread of Antibiotic Resistance. The World Health Organization has declared the emergence of antibiotic resistance to be a global threat to human health. Broad-host-range plasmids have a key role in causing this health crisis because they transfer multiple resistance genes to a wide range of bacteria. To limit the spread of antibiotic resistance, we need to gain insight into the mechanisms by which the host range of plasmids evolves. Although initially unstable plasmids have been shown to improve their persistence through evolution of the plasmid, the host, or both, the means by which this occurs are poorly understood. Here, we sought to identify the underlying genetic basis of expanded plasmid host-range and increased persistence of an antibiotic resistance plasmid using a combined experimental-modeling approach that included whole-genome resequencing, molecular genetics and a plasmid population dynamics model. In nine of the ten previously evolved clones, changes in host and plasmid each slightly improved plasmid persistence, but their combination resulted in a much larger improvement, which indicated positive epistasis. The only genetic change in the plasmid was the acquisition of a transposable element from a plasmid native to the Pseudomonas host used in these studies. The analysis of genetic deletions showed that the critical genes on this transposon encode a putative toxin-antitoxin (TA) and a cointegrate resolution system. As evolved plasmids were able to persist longer in multiple naïve hosts, acquisition of this transposon also expanded the plasmid's host range, which has important implications for the spread of antibiotic resistance. | 2016 | 26668183 |
| 9829 | 8 | 0.9998 | Promiscuous transfer of drug resistance in gram-negative bacteria. Bacterial conjugation is a major mechanism for the spread of antibiotic-resistance genes in pathogenic organisms. In gram-negative bacteria, broad-host-range drug-resistance plasmids mediate genetic exchange between many unrelated species. The mechanism of conjugation encoded by the broad-host-range IncP plasmid RK2 has been studied in detail. The location and sequence of the transfer origin of RK2 has been determined. Several barriers limit plasmid transfer between unrelated bacteria: interactions at the cell surface may prevent effective mating contact, restriction systems may degrade foreign DNA, or the plasmid may not replicate in the new host. RK2 has evolved specific mechanisms by which it overcomes these barriers; this plasmid can mediate the transfer of resistance to most gram-negative bacteria. | 1984 | 6143782 |
| 9275 | 9 | 0.9998 | Bacteriophage selection against a plasmid-encoded sex apparatus leads to the loss of antibiotic-resistance plasmids. Antibiotic-resistance genes are often carried by conjugative plasmids, which spread within and between bacterial species. It has long been recognized that some viruses of bacteria (bacteriophage; phage) have evolved to infect and kill plasmid-harbouring cells. This raises a question: can phages cause the loss of plasmid-associated antibiotic resistance by selecting for plasmid-free bacteria, or can bacteria or plasmids evolve resistance to phages in other ways? Here, we show that multiple antibiotic-resistance genes containing plasmids are stably maintained in both Escherichia coli and Salmonella enterica in the absence of phages, while plasmid-dependent phage PRD1 causes a dramatic reduction in the frequency of antibiotic-resistant bacteria. The loss of antibiotic resistance in cells initially harbouring RP4 plasmid was shown to result from evolution of phage resistance where bacterial cells expelled their plasmid (and hence the suitable receptor for phages). Phages also selected for a low frequency of plasmid-containing, phage-resistant bacteria, presumably as a result of modification of the plasmid-encoded receptor. However, these double-resistant mutants had a growth cost compared with phage-resistant but antibiotic-susceptible mutants and were unable to conjugate. These results suggest that bacteriophages could play a significant role in restricting the spread of plasmid-encoded antibiotic resistance. | 2011 | 21632619 |
| 9688 | 10 | 0.9998 | Indirect Selection against Antibiotic Resistance via Specialized Plasmid-Dependent Bacteriophages. Antibiotic resistance genes of important Gram-negative bacterial pathogens are residing in mobile genetic elements such as conjugative plasmids. These elements rapidly disperse between cells when antibiotics are present and hence our continuous use of antimicrobials selects for elements that often harbor multiple resistance genes. Plasmid-dependent (or male-specific or, in some cases, pilus-dependent) bacteriophages are bacterial viruses that infect specifically bacteria that carry certain plasmids. The introduction of these specialized phages into a plasmid-abundant bacterial community has many beneficial effects from an anthropocentric viewpoint: the majority of the plasmids are lost while the remaining plasmids acquire mutations that make them untransferable between pathogens. Recently, bacteriophage-based therapies have become a more acceptable choice to treat multi-resistant bacterial infections. Accordingly, there is a possibility to utilize these specialized phages, which are not dependent on any particular pathogenic species or strain but rather on the resistance-providing elements, in order to improve or enlengthen the lifespan of conventional antibiotic approaches. Here, we take a snapshot of the current knowledge of plasmid-dependent bacteriophages. | 2021 | 33572937 |
| 9677 | 11 | 0.9998 | Inhibiting conjugation as a tool in the fight against antibiotic resistance. Antibiotic resistance, especially in gram-negative bacteria, is spreading globally and rapidly. Development of new antibiotics lags behind; therefore, novel approaches to the problem of antibiotic resistance are sorely needed and this commentary highlights one relatively unexplored target for drug development: conjugation. Conjugation is a common mechanism of horizontal gene transfer in bacteria that is instrumental in the spread of antibiotic resistance among bacteria. Most resistance genes are found on mobile genetic elements and primarily spread by conjugation. Furthermore, conjugative elements can act as a reservoir to maintain antibiotic resistance in the bacterial population even in the absence of antibiotic selection. Thus, conjugation can spread antibiotic resistance quickly between bacteria of the microbiome and pathogens when selective pressure (antibiotics) is introduced. Potential drug targets include the plasmid-encoded conjugation system and the host-encoded proteins important for conjugation. Ideally, a conjugation inhibitor will be used alongside antibiotics to prevent the spread of resistance to or within pathogens while not acting as a growth inhibitor itself. Inhibiting conjugation will be an important addition to our arsenal of strategies to combat the antibiotic resistance crisis, allowing us to extend the usefulness of antibiotics. | 2019 | 30343487 |
| 9308 | 12 | 0.9998 | Integrons: natural tools for bacterial genome evolution. Integrons were first identified as the primary mechanism for antibiotic resistance gene capture and dissemination among Gram-negative bacteria. More recently, their role in genome evolution has been extended with the discovery of larger integron structures, the super-integrons, as genuine components of the genomes of many species throughout the gamma-proteobacterial radiation. The functional platforms of these integrons appear to be sedentary, whereas their gene cassette contents are highly variable. Nevertheless, the gene cassettes for which an activity has been experimentally demonstrated encode proteins related to simple adaptive functions and their recruitment is seen as providing the bacterial host with a selective advantage. The widespread occurrence of the integron system among Gram-negative bacteria is discussed, with special focus on the super-integrons. Some of the adaptive functions encoded by these genes are also reviewed, and implications of integron-mediated genome evolution in the emergence of novel bacterial species are highlighted. | 2001 | 11587934 |
| 9245 | 13 | 0.9998 | Type IV Coupling Proteins as Potential Targets to Control the Dissemination of Antibiotic Resistance. The increase of infections caused by multidrug-resistant bacteria, together with the loss of effectiveness of currently available antibiotics, represents one of the most serious threats to public health worldwide. The loss of human lives and the economic costs associated to the problem of the dissemination of antibiotic resistance require immediate action. Bacteria, known by their great genetic plasticity, are capable not only of mutating their genes to adapt to disturbances and environmental changes but also of acquiring new genes that allow them to survive in hostile environments, such as in the presence of antibiotics. One of the major mechanisms responsible for the horizontal acquisition of new genes (e.g., antibiotic resistance genes) is bacterial conjugation, a process mediated by mobile genetic elements such as conjugative plasmids and integrative conjugative elements. Conjugative plasmids harboring antibiotic resistance genes can be transferred from a donor to a recipient bacterium in a process that requires physical contact. After conjugation, the recipient bacterium not only harbors the antibiotic resistance genes but it can also transfer the acquired plasmid to other bacteria, thus contributing to the spread of antibiotic resistance. Conjugative plasmids have genes that encode all the proteins necessary for the conjugation to take place, such as the type IV coupling proteins (T4CPs) present in all conjugative plasmids. Type VI coupling proteins constitute a heterogeneous family of hexameric ATPases that use energy from the ATP hydrolysis for plasmid transfer. Taking into account their essential role in bacterial conjugation, T4CPs are attractive targets for the inhibition of bacterial conjugation and, concomitantly, the limitation of antibiotic resistance dissemination. This review aims to compile present knowledge on T4CPs as a starting point for delving into their molecular structure and functioning in future studies. Likewise, the scientific literature on bacterial conjugation inhibitors has been reviewed here, in an attempt to elucidate the possibility of designing T4CP-inhibitors as a potential solution to the dissemination of multidrug-resistant bacteria. | 2020 | 32903459 |
| 9305 | 14 | 0.9998 | Control of genes for conjugative transfer of plasmids and other mobile elements. Conjugative transfer is a primary means of spread of mobile genetic elements (plasmids and transposons) between bacteria.It leads to the dissemination and evolution of the genes (such as those conferring resistance to antibiotics) which are carried by the plasmid. Expression of the plasmid genes needed for conjugative transfer is tightly regulated so as to minimise the burden on the host. For plasmids such as those belonging to the IncP group this results in downregulation of the transfer genes once all bacteria have a functional conjugative apparatus. For F-like plasmids (apart from F itself which is a derepressed mutant) tight control results in very few bacteria having a conjugative apparatus. Chance encounters between the rare transfer-proficient bacteria and a potential recipient initiate a cascade of transfer which can continue until all potential recipients have acquired the plasmid. Other systems express their transfer genes in response to specific stimuli. For the pheromone-responsive plasmids of Enterococcus it is small peptide signals from potential recipients which trigger the conjugative transfer genes. For the Ti plasmids of Agrobacterium it is the presence of wounded plants which are susceptible to infection which stimulates T-DNA transfer to plants. Transfer and integration of T-DNA induces production of opines which the plasmid-positive bacteria can utilise. They multiply and when they reach an appropriate density their plasmid transfer system is switched on to allow transfer of the Ti plasmid to other bacteria. Finally some conjugative transfer systems are induced by the antibiotics to which the elements confer resistance. Understanding these control circuits may help to modify management of microbial communities where plasmid transfer is either desirable or undesirable. z 1998 Published by Elsevier Science B.V. | 1998 | 25508777 |
| 9679 | 15 | 0.9998 | Integrons as the potential targets for combating multidrug resistance in Enterobacteriaceae using CRISPR- Cas9 technique. The emergence of multi-drug resistance (MDR) to pan-drug resistance (PDR) in Enterobacteriaceae has made treatment extremely challenging. Genetic mutations and horizontal gene transfer (HGT) through mobile genetic elements (MGEs) were frequently associated mechanisms of drug resistance in pathogens. However, transposons, plasmids, and integrons transfer MDR genes in bacterium via HGT much faster. Integrons are dsDNA segment that plays a crucial role in the adaptation and evolution of bacteria. They contain multiple gene cassettes that code for antibiotic resistance determinants that are expressed by a single promoter (Pc). Integrons are the cause of drug resistance in Enterobacteriaceae. Although alternatives to antibiotics such as bacteriophages, phage proteins, antimicrobial peptides, and natural compounds have been widely used to treat MDR infections, there have been limited efforts to reverse the antibiotic resistance ability of bacteria. Thus, silencing the genes harboured on MGEs achieved by Gene Editing Techniques (GETs) might prevent the spread of MDR. One such GETs, which has a simple design, good repeatability, low cost, and high efficiency, is CRISPR- Cas9 system. Thus, this review is a first of the kind that focuses on utilizing the structure of an integron to make it an ideal target for GETs like CRISPR- Cas9 systems. | 2023 | 37410611 |
| 9314 | 16 | 0.9998 | Phage Transduction of Staphylococcus aureus. Bacteriophage transduction is the major mechanism of horizontal gene transfer (HGT) among many bacteria. In Staphylococcus aureus, the phage-mediated acquisition of mobile genetic elements (MGEs) that encode virulence and antibiotic resistance genes largely contribute to its evolutionary adaptation and genetic plasticity. In molecular biology, generalized transduction is routinely used as a technique to manipulate and construct bacterial strains. Here, we describe optimized protocols for generalized transduction, applicable for the transfer of plasmid or chromosomal deoxyribonucleic acid (DNA) from donor to recipient S. aureus strains. | 2024 | 37966605 |
| 4131 | 17 | 0.9998 | R plasmid transfer. This paper is a brief survey of the systems of genetic exchange in bacteria relevant to the spread of antibiotic resistance genes. Emphasis is given to those systems most likely to be important in nature, particularly conjugation. Several recently described examples of conjugation in Gram-positive bacteria are discussed and contrasted with the better studied examples in Gram-negative bacteria. | 1986 | 3542931 |
| 9398 | 18 | 0.9998 | Effectiveness of CRISPR-Cas in Sensitizing Bacterial Populations with Plasmid-Encoded Antimicrobial Resistance. The spread of bacteria resistant to antibiotics poses a serious threat to human health. Genes that encode antibiotic resistance are often harbored on plasmids, extra-chromosomal DNA molecules found in bacteria. The emergence of multiresistance plasmids is particularly problematic and demands the development of new antibiotics and alternative strategies. CRISPR-Cas derived tools with their sequence specificity offer a promising new approach to combating antibiotic resistance. By introducing CRISPR-Cas encoding plasmids that %specifically target antibiotic resistance genes on plasmids, the susceptibility of bacteria to conventional antibiotics can be restored. However, genetic variation within bacterial populations can hinder the effectiveness of such CRISPR-Cas tools by allowing some mutant plasmids to evade CRISPR-mediated cleaving or gene silencing. In this study, we develop a model to test the effectiveness of CRISPR-Cas in sensitizing bacterial populations carrying resistance on non-transmissible plasmids and assess the success probability of a subsequent treatment with conventional antibiotics. We evaluate this probability according to the target interference mechanism, the copy number of the resistance-encoding plasmid, and its compatibility with the CRISPR-Cas encoding plasmid. Our results identify promising approaches to revert antibiotic resistance with CRISPR-Cas encoding plasmids: A DNA-cleaving CRISPR-Cas system on a plasmid incompatible with the targeted plasmid is most effective for low copy numbers, while for resistance plasmids with higher copy numbers gene silencing by CRISPR-Cas systems encoded on compatible plasmids is the superior solution. | 2025 | 40985758 |
| 4168 | 19 | 0.9997 | Various pathways leading to the acquisition of antibiotic resistance by natural transformation. Natural transformation can lead to exchange of DNA between taxonomically diverse bacteria. In the case of chromosomal DNA, homology-based recombination with the recipient genome is usually necessary for heritable stability. In our recent study, we have shown that natural transformation can promote the transfer of transposons, IS elements, and integrons and gene cassettes, largely independent of the genetic relationship between the donor and recipient bacteria. Additional results from our study suggest that natural transformation with species-foreign DNA might result in the uptake of a wide range of DNA fragments; leading to changes in the antimicrobial susceptibility profile and contributing to the generation of antimicrobial resistance in bacteria. | 2012 | 23482877 |