# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 9241 | 0 | 0.9963 | Evolutionary Mechanisms Shaping the Maintenance of Antibiotic Resistance. Antibiotics target essential cellular functions but bacteria can become resistant by acquiring either exogenous resistance genes or chromosomal mutations. Resistance mutations typically occur in genes encoding essential functions; these mutations are therefore generally detrimental in the absence of drugs. However, bacteria can reduce this handicap by acquiring additional mutations, known as compensatory mutations. Genetic interactions (epistasis) either with the background or between resistances (in multiresistant bacteria) dramatically affect the fitness cost of antibiotic resistance and its compensation, therefore shaping dissemination of antibiotic resistance mutations. This Review summarizes current knowledge on the evolutionary mechanisms influencing maintenance of resistance mediated by chromosomal mutations, focusing on their fitness cost, compensatory evolution, epistasis, and the effect of the environment on these processes. | 2018 | 29439838 |
| 9525 | 1 | 0.9963 | Is there a serious risk of resistance development to azoles among fungi due to the widespread use and long-term application of azole antifungals in medicine? It is well known that development of antibiotic resistance in bacteria is not a matter of if but of when. Recently, azoles have been recommended for long-term prophylaxis of invasive fungal infections; hence, it could be argued that fungi also will become resistant to these agents. However, fungi are different from bacteria in several critical points. Bacteria display several resistance mechanisms: alteration of the target, limited access to the target and modification/inactivation of the antibacterial compound. In fungi some mechanisms of resistance to azoles are also known; with azoles for example, alterations of the 14alpha-demethylase target, as well as efflux pumps. It has been observed that these phenotypes develop in yeast populations either due to mutations or to selection processes. However, enzymes which destroy azoles are not found. Furthermore, a horizontal transfer of genes coding resistance traits does not occur in fungi, which means that an explosive expansion of resistances is unlikely to occur, especially in moulds. Indeed, in epidemiologic studies on human and environmental isolates there is convincing evidence that azole resistance is quite uncommon. | 2008 | 18325827 |
| 9490 | 2 | 0.9962 | The superbugs: evolution, dissemination and fitness. Since the introduction of antibiotics, bacteria have not only evolved elegant resistance mechanisms to thwart their effect, but have also evolved ways in which to disseminate themselves or their resistance genes to other susceptible bacteria. During the past few years, research has revealed not only how such resistance mechanisms have been able to evolve and to rapidly disseminate, but also how bacteria have, in some cases, been able to adapt to this new burden of resistance with little or no cost to their fitness. Such adaptations make the control of these superbugs all the more difficult. | 1998 | 10066531 |
| 9582 | 3 | 0.9961 | Humans and Microbes: A Systems Theory Perspective on Coevolution. The issue of rapid adaptation of microorganisms to changing environments is examined. The mechanism of adaptive mutations is analyzed. The possibility that horizontal gene transfer is a random process is discussed. Bacteria, unicellular fungi, and other microorganisms successfully adapt to fast-changing conditions (such as exposure to drugs) because their evolution is not a random process. Adaptation to antibiotics, adaptive mutations, and related phenomena occur because microbial evolution is inherently directed and purposefully oriented toward potential external changes. Rejecting gene-centricity plays a crucial role in understanding the coevolution of humans and pathogens. This means that beyond genes, there exists a higher-level system-an organism with its own unique properties that cannot be reduced to genes. The problem of human adaptation to infectious agents (viruses, bacteria, and protozoa) is also analyzed. Based on general systems theory, it is concluded that humans and pathogens coevolve in a controlled manner. | 2025 | 41176022 |
| 9173 | 4 | 0.9961 | Bacterial defences: mechanisms, evolution and antimicrobial resistance. Throughout their evolutionary history, bacteria have faced diverse threats from other microorganisms, including competing bacteria, bacteriophages and predators. In response to these threats, they have evolved sophisticated defence mechanisms that today also protect bacteria against antibiotics and other therapies. In this Review, we explore the protective strategies of bacteria, including the mechanisms, evolution and clinical implications of these ancient defences. We also review the countermeasures that attackers have evolved to overcome bacterial defences. We argue that understanding how bacteria defend themselves in nature is important for the development of new therapies and for minimizing resistance evolution. | 2023 | 37095190 |
| 9586 | 5 | 0.9960 | Antibiotic resistance. Through billions of years of evolution, microbes have developed myriad defense mechanisms designed to ensure their survival. This protection is readily transferred to their fellow life forms via transposable elements. Despite very early warnings, humans have chosen to abuse the gift of antibiotics and have created a situation where all microorganisms are resistant to some antibiotics and some microorganisms are resistant to all antibiotics. When antibiotics are used, six events may occur with only one being beneficial: when the antibiotic aids the host defenses to gain control and eliminate the infection. Alternatively, the antibiotic may cause toxicity or allergy, initiate a superinfection with resistant bacteria, promote microbial chromosomal mutations to resistance, encourage resistance gene transfer to susceptible species, or promote the expression of dormant resistance genes. | 2003 | 14664456 |
| 9526 | 6 | 0.9960 | Will resistance in fungi emerge on a scale similar to that seen in bacteria? Growing numbers of patients receive azoles as prophylaxis or treatment for invasive fungal infections, begging the question of whether emergence of resistance will occur, as has been seen with bacteria. This review examines resistance pathways shared by bacteria and fungi, including alteration and overproduction of drug targets, changes in biosynthetic pathways, and enhanced drug efflux, and assesses whether such commonalities predict increased resistance to azoles. Important differences exist between the two kingdoms, including little, if any, horizontal transfer of extrachromosomal material across fungal species and a longer fungal generation time, thereby slowing vertical transfer of mutant traits. Further, no enzymatic modulation or inactivation of azoles has been reported in fungi. The newer broad-spectrum azoles posaconazole and voriconazole are active against the vast majority of yeasts and moulds and are likely to prevent the emergence of inherently resistant strains. Therefore, the likelihood for an explosion of fungal resistance is relatively low. | 2008 | 18204870 |
| 9130 | 7 | 0.9960 | Glycopeptide antibiotic resistance. Glycopeptide antibiotics are integral components of the current antibiotic arsenal that is under strong pressures as a result of the emergence of a variety of resistance mechanisms over the past 15 years. Resistance has manifested itself largely through the expression of genes that encode proteins that reprogram cell wall biosynthesis and thus evade the action of the antibiotic in the enterococci, though recently new mechanisms have appeared that afford resistance and tolerance in the more virulent staphylococci and streptococci. Overcoming glycopeptide resistance will require innovative approaches to generate new antibiotics or otherwise to inhibit the action of resistance elements in various bacteria. The chemical complexity of the glycopeptides, the challenges of discovering and successfully exploiting new targets, and the growing number of distinct resistance types all increase the difficulty of the current problem we face as a result of the emergence of glycopeptide resistance. | 2002 | 11807177 |
| 9481 | 8 | 0.9960 | Genetic linkage and horizontal gene transfer, the roots of the antibiotic multi-resistance problem. Bacteria carrying resistance genes for many antibiotics are moving beyond the clinic into the community, infecting otherwise healthy people with untreatable and frequently fatal infections. This state of affairs makes it increasingly important that we understand the sources of this problem in terms of bacterial biology and ecology and also that we find some new targets for drugs that will help control this growing epidemic. This brief and eclectic review takes the perspective that we have too long thought about the problem in terms of treatment with or resistance to a single antibiotic at a time, assuming that dissemination of the resistance gene was affected by simple vertical inheritance. In reality antibiotic resistance genes are readily transferred horizontally, even to and from distantly related bacteria. The common agents of bacterial gene transfer are described and also one of the processes whereby nonantibiotic chemicals, specifically toxic metals, in the environment can select for and enrich bacteria with antibiotic multiresistance. Lastly, some speculation is offered on broadening our perspective on this problem to include drugs directed at compromising the ability of the mobile elements themselves to replicate, transfer, and recombine, that is, the three "infrastructure" processes central to the movement of genes among bacteria. | 2006 | 17127524 |
| 8238 | 9 | 0.9960 | Resistance to enediyne antitumor antibiotics by CalC self-sacrifice. Antibiotic self-resistance mechanisms, which include drug elimination, drug modification, target modification, and drug sequestration, contribute substantially to the growing problem of antibiotic resistance among pathogenic bacteria. Enediynes are among the most potent naturally occurring antibiotics, yet the mechanism of resistance to these toxins has remained a mystery. We characterize an enediyne self-resistance protein that reveals a self-sacrificing paradigm for resistance to highly reactive antibiotics, and thus another opportunity for nonpathogenic or pathogenic bacteria to evade extremely potent small molecules. | 2003 | 12970566 |
| 9710 | 10 | 0.9960 | Horizontal gene transfer as a biosafety issue: a natural phenomenon of public concern. The transfer of genetic information between distantly or even unrelated organisms during evolution had been inferred from nucleotide sequence comparisons. These studies provided circumstantial evidence that in rare cases genes had been laterally transmitted amongst organisms of the domains bacteria, archaea and eukarya. Laboratory-based studies confirmed that the gene pools of the various domains of organisms are linked. Amongst the bacterial gene exchange mechanisms transduction, transformation and conjugation, the latter was identified as the mechanism with potentially the broadest host range of transfer. Previously, the issue of horizontal gene transfer has become important in the context of biosafety. Gene transfer studies carried out under more natural conditions such as in model ecosystems or in the environment established that all gene transfer mechanisms worked under these conditions. Moreover, environmental hot-spots were identified where favourable conditions such as nutrient enrichment increased the probability of genetic exchange among bacteria. In particular, the phytosphere was shown to provide conducive conditions for conjugative gene exchange. Concern has been expressed that transfer of recombinant DNA (e.g. antibiotic resistance genes) from genetically modified organisms (GMOs) such as transgenic plants to phytosphere bacteria may occur and thus contribute to the undesirable spread of antibiotic resistance determinants. Studies which were performed to address this issue clearly showed that such a transfer occurs, if at all, at extremely low frequency. | 1998 | 9823660 |
| 9285 | 11 | 0.9960 | Bacterial genetic exchange in nature. Most bacteria are haploid organisms containing only one copy of each gene per cell for most of the growth cycle. This means that the chance for correcting random mutations in bacterial genes would depend entirely on the complementarity inherent in DNA structures, unless homologous DNA sequences can be imported from outside the cell. Bacteria, like all living organisms have evolved at least one autonomous mechanism, conjugation, for exchanging portions of genetic materials between two related cells. The ecological benefits of conjugation include the expansion of metabolic versatility and resistance to hazardous environmental conditions. Natural bacterial genetic exchange also occurs through virus infections (transduction) and through the uptake of extracellular DNA (transformation). The origin and ecological benefits of transduction and transformation are difficult to assess because they are driven by factors external to the affected cell. Bacterial genetic exchange has implications for the evolution of phenotypes that are either beneficial to humans, such as biodegradation of toxic xenobiotic chemicals, or that are detrimental, such as the evolution of pathogenesis and the spread of antibiotic resistance. Understanding natural bacterial genetic exchange mechanisms is also relevant to the assessment of dispersal risks associated with genetically engineered bacteria and recombinant genes in the environment. | 1995 | 8533067 |
| 9284 | 12 | 0.9959 | The population and evolutionary dynamics of homologous gene recombination in bacterial populations. In bacteria, recombination is a rare event, not a part of the reproductive process. Nevertheless, recombination -- broadly defined to include the acquisition of genes from external sources, i.e., horizontal gene transfer (HGT) -- plays a central role as a source of variation for adaptive evolution in many species of bacteria. Much of niche expansion, resistance to antibiotics and other environmental stresses, virulence, and other characteristics that make bacteria interesting and problematic, is achieved through the expression of genes and genetic elements obtained from other populations of bacteria of the same and different species, as well as from eukaryotes and archaea. While recombination of homologous genes among members of the same species has played a central role in the development of the genetics and molecular biology of bacteria, the contribution of homologous gene recombination (HGR) to bacterial evolution is not at all clear. Also, not so clear are the selective pressures responsible for the evolution and maintenance of transformation, the only bacteria-encoded form of HGR. Using a semi-stochastic simulation of mutation, recombination, and selection within bacterial populations and competition between populations, we explore (1) the contribution of HGR to the rate of adaptive evolution in these populations and (2) the conditions under which HGR will provide a bacterial population a selective advantage over non-recombining or more slowly recombining populations. The results of our simulation indicate that, under broad conditions: (1) HGR occurring at rates in the range anticipated for bacteria like Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae, and Bacillus subtilis will accelerate the rate at which a population adapts to environmental conditions; (2) once established in a population, selection for this capacity to increase rates of adaptive evolution can maintain bacteria-encoded mechanisms of recombination and prevent invasion of non-recombining populations, even when recombination engenders a modest fitness cost; and (3) because of the density- and frequency-dependent nature of HGR in bacteria, this capacity to increase rates of adaptive evolution is not sufficient as a selective force to provide a recombining population a selective advantage when it is rare. Under realistic conditions, homologous gene recombination will increase the rate of adaptive evolution in bacterial populations and, once established, selection for higher rates of evolution will promote the maintenance of bacteria-encoded mechanisms for HGR. On the other hand, increasing rates of adaptive evolution by HGR is unlikely to be the sole or even a dominant selective pressure responsible for the original evolution of transformation. | 2009 | 19680442 |
| 9385 | 13 | 0.9959 | A generalised model for generalised transduction: the importance of co-evolution and stochasticity in phage mediated antimicrobial resistance transfer. Antimicrobial resistance is a major global challenge. Of particular concern are mobilizable elements that can transfer resistance genes between bacteria, leading to pathogens with new combinations of resistance. To date, mathematical models have largely focussed on transfer of resistance by plasmids, with fewer studies on transfer by bacteriophages. We aim to understand how best to model transfer of resistance by transduction by lytic phages. We show that models of lytic bacteriophage infection with empirically derived realistic phage parameters lead to low numbers of bacteria, which, in low population or localised environments, lead to extinction of bacteria and phage. Models that include antagonistic co-evolution of phage and bacteria produce more realistic results. Furthermore, because of these low numbers, stochastic dynamics are shown to be important, especially to spread of resistance. When resistance is introduced, resistance can sometimes be fixed, and at other times die out, with the probability of each outcome sensitive to bacterial and phage parameters. Specifically, that outcome most strongly depends on the baseline death rate of bacteria, with phage-mediated spread favoured in benign environments with low mortality over more hostile environments. We conclude that larger-scale models should consider spatial compartmentalisation and heterogeneous microenviroments, while encompassing stochasticity and co-evolution. | 2020 | 32490523 |
| 9131 | 14 | 0.9959 | How do antibiotic-producing bacteria ensure their self-resistance before antibiotic biosynthesis incapacitates them? Acquired antibiotic resistance among dangerous bacterial pathogens is an increasing medical problem. While in Mycobacterium tuberculosis this occurs by mutation in the genes encoding the targets for antibiotic action, other pathogens have generally gained their resistance genes by horizontal gene transfer from non-pathogenic bacteria. The ultimate source of many of these genes is almost certainly the actinomycetes that make the antibiotics and therefore need self-protective mechanisms to avoid suicide. How do they ensure that they are resistant at the time when intracellular antibiotic concentrations reach potentially lethal levels? In this issue of Molecular Microbiology, Tahlan et al. describe a solution to this problem in which an antibiotically inactive precursor of a Streptomyces coelicolor antibiotic induces resistance -- in this example by means of a trans-membrane export pump -- so that the organism is already primed for resistance at the time when it is needed. The authors generalize their interpretation to other cases where antibiotic resistance depends on export, but it will be interesting to find out whether it could in fact apply more widely, to include the other major mechanisms of resistance: target modification and the synthesis of antibiotics via a series of chemically modified intermediates, with removal of the protective group at the time of secretion into the outside medium. | 2007 | 17238916 |
| 9489 | 15 | 0.9959 | The origins of antibiotic resistance. Antibiotics remain one of our most important pharmacological tools for the control of infectious disease. However, unlike most other drugs, the use of antibiotics selects for resistant organisms and erodes their clinical utility. Resistance can emerge within populations of bacteria by mutation and be retained by subsequent selection or by the acquisition of resistance elements laterally from other organisms. The source of these resistance genes is only now being understood. The evidence supports a large bacterial resistome-the collection of all resistance genes and their precursors in both pathogenic and nonpathogenic bacteria. These genes have arisen by various means including self-protection in the case of antibiotic producers, transport of small molecules for various reasons including nutrition and detoxification of noxious chemicals, and to accomplish other goals, such as metabolism, and demonstrate serendipitous selectivity for antibiotics. Regardless of their origins, resistance genes can rapidly move through bacterial populations and emerge in pathogenic bacteria. Understanding the processes that contribute to the evolution and selection of resistance is essential to mange current stocks of antibiotics and develop new ones. | 2012 | 23090593 |
| 9382 | 16 | 0.9959 | The evolution of mutator genes in bacterial populations: the roles of environmental change and timing. Recent studies have found high frequencies of bacteria with increased genomic rates of mutation in both clinical and laboratory populations. These observations may seem surprising in light of earlier experimental and theoretical studies. Mutator genes (genes that elevate the genomic mutation rate) are likely to induce deleterious mutations and thus suffer an indirect selective disadvantage; at the same time, bacteria carrying them can increase in frequency only by generating beneficial mutations at other loci. When clones carrying mutator genes are rare, however, these beneficial mutations are far more likely to arise in members of the much larger nonmutator population. How then can mutators become prevalent? To address this question, we develop a model of the population dynamics of bacteria confronted with ever-changing environments. Using analytical and simulation procedures, we explore the process by which initially rare mutator alleles can rise in frequency. We demonstrate that subsequent to a shift in environmental conditions, there will be relatively long periods of time during which the mutator subpopulation can produce a beneficial mutation before the ancestral subpopulations are eliminated. If the beneficial mutation arises early enough, the overall frequency of mutators will climb to a point higher than when the process began. The probability of producing a subsequent beneficial mutation will then also increase. In this manner, mutators can increase in frequency over successive selective sweeps. We discuss the implications and predictions of these theoretical results in relation to antibiotic resistance and the evolution of mutation rates. | 2003 | 12871898 |
| 9588 | 17 | 0.9959 | Bacteriophage-host arm race: an update on the mechanism of phage resistance in bacteria and revenge of the phage with the perspective for phage therapy. Due to a constant attack by phage, bacteria in the environment have evolved diverse mechanisms to defend themselves. Several reviews on phage resistance mechanisms have been published elsewhere. Thanks to the advancement of molecular techniques, several new phage resistance mechanisms were recently identified. For the practical phage therapy, the emergence of phage-resistant bacteria could be an obstacle. However, unlike antibiotic, phages could evolve a mechanism to counter-adapt against phage-resistant bacteria. In this review, we summarized the most recent studies of the phage-bacteria arm race with the perspective of future applications of phages as antimicrobial agents. | 2019 | 30680434 |
| 9491 | 18 | 0.9959 | Mutation and evolution of antibiotic resistance: antibiotics as promoters of antibiotic resistance? Antibiotic resistance appearance and spread have been classically considered the result of a process of natural selection, directed by the use of antibiotics. Bacteria, that have to face the antibiotic challenge, evolve to acquire resistance and, under this strong selective pressure, only the fittest survive, leading to the spread of resistance mechanisms and resistant clones. Horizontal transference of resistance mechanisms seems to be the main way of antibiotic resistance acquisition. Nevertheless, recent findings on hypermutability and antibiotic-induced hypermutation in bacteria have modified the landscape. Here, we present a review of the last data on molecular mechanisms of hypermutability in bacteria and their relationship with the acquisition of antibiotic resistance. Finally, we discuss the possibility that antibiotics may act not only as selectors for antibiotic resistant bacteria but also as resistance promoters. | 2002 | 12102604 |
| 9493 | 19 | 0.9959 | Regulatory integration of horizontally-transferred genes in bacteria. Horizontal transfer of genetic material is a fact of microbial life and bacteria can obtain new DNA sequences through the processes of conjugation, transduction and transformation. This offers the bacterium the possibility of evolving rapidly by importing new genes that code for new traits that may assist in environmental adaptation. Research in this area has focused in particular on the role of horizontal transfer in the dissemination through bacterial populations of genes for resistance to antimicrobial agents, including antibiotics. It is becoming clear that many other phenotypic characteristics have been acquired through horizontal routes and that these include traits contributing to pathogenesis and symbiosis. An important corollary to the acquisition of new genes is the problem of how best to integrate them in the existing gene regulatory circuits of the recipient so that fitness is not compromised initially and can be enhanced in the future through optimal expression of the new genes. | 2009 | 19273337 |