# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 8422 | 0 | 0.9957 | Slightly beneficial genes are retained by bacteria evolving DNA uptake despite selfish elements. Horizontal gene transfer (HGT) and gene loss result in rapid changes in the gene content of bacteria. While HGT aids bacteria to adapt to new environments, it also carries risks such as selfish genetic elements (SGEs). Here, we use modelling to study how HGT of slightly beneficial genes impacts growth rates of bacterial populations, and if bacterial collectives can evolve to take up DNA despite selfish elements. We find four classes of slightly beneficial genes: indispensable, enrichable, rescuable, and unrescuable genes. Rescuable genes - genes with small fitness benefits that are lost from the population without HGT - can be collectively retained by a community that engages in costly HGT. While this 'gene-sharing' cannot evolve in well-mixed cultures, it does evolve in a spatial population like a biofilm. Despite enabling infection by harmful SGEs, the uptake of foreign DNA is evolutionarily maintained by the hosts, explaining the coexistence of bacteria and SGEs. | 2020 | 32432548 |
| 8264 | 1 | 0.9956 | Anti-CRISPR Phages Cooperate to Overcome CRISPR-Cas Immunity. Some phages encode anti-CRISPR (acr) genes, which antagonize bacterial CRISPR-Cas immune systems by binding components of its machinery, but it is less clear how deployment of these acr genes impacts phage replication and epidemiology. Here, we demonstrate that bacteria with CRISPR-Cas resistance are still partially immune to Acr-encoding phage. As a consequence, Acr-phages often need to cooperate in order to overcome CRISPR resistance, with a first phage blocking the host CRISPR-Cas immune system to allow a second Acr-phage to successfully replicate. This cooperation leads to epidemiological tipping points in which the initial density of Acr-phage tips the balance from phage extinction to a phage epidemic. Furthermore, both higher levels of CRISPR-Cas immunity and weaker Acr activities shift the tipping points toward higher initial phage densities. Collectively, these data help elucidate how interactions between phage-encoded immune suppressors and the CRISPR systems they target shape bacteria-phage population dynamics. | 2018 | 30033365 |
| 9173 | 2 | 0.9955 | 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 |
| 8267 | 3 | 0.9955 | Why put up with immunity when there is resistance: an excursion into the population and evolutionary dynamics of restriction-modification and CRISPR-Cas. Bacteria can readily generate mutations that prevent bacteriophage (phage) adsorption and thus make bacteria resistant to infections with these viruses. Nevertheless, the majority of bacteria carry complex innate and/or adaptive immune systems: restriction-modification (RM) and CRISPR-Cas, respectively. Both RM and CRISPR-Cas are commonly assumed to have evolved and be maintained to protect bacteria from succumbing to infections with lytic phage. Using mathematical models and computer simulations, we explore the conditions under which selection mediated by lytic phage will favour such complex innate and adaptive immune systems, as opposed to simple envelope resistance. The results of our analysis suggest that when populations of bacteria are confronted with lytic phage: (i) In the absence of immunity, resistance to even multiple bacteriophage species with independent receptors can evolve readily. (ii) RM immunity can benefit bacteria by preventing phage from invading established bacterial populations and particularly so when there are multiple bacteriophage species adsorbing to different receptors. (iii) Whether CRISPR-Cas immunity will prevail over envelope resistance depends critically on the number of steps in the coevolutionary arms race between the bacteria-acquiring spacers and the phage-generating CRISPR-escape mutants. We discuss the implications of these results in the context of the evolution and maintenance of RM and CRISPR-Cas and highlight fundamental questions that remain unanswered. This article is part of a discussion meeting issue 'The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems'. | 2019 | 30905282 |
| 9174 | 4 | 0.9954 | Developing Phage Therapy That Overcomes the Evolution of Bacterial Resistance. The global rise of antibiotic resistance in bacterial pathogens and the waning efficacy of antibiotics urge consideration of alternative antimicrobial strategies. Phage therapy is a classic approach where bacteriophages (bacteria-specific viruses) are used against bacterial infections, with many recent successes in personalized medicine treatment of intractable infections. However, a perpetual challenge for developing generalized phage therapy is the expectation that viruses will exert selection for target bacteria to deploy defenses against virus attack, causing evolution of phage resistance during patient treatment. Here we review the two main complementary strategies for mitigating bacterial resistance in phage therapy: minimizing the ability for bacterial populations to evolve phage resistance and driving (steering) evolution of phage-resistant bacteria toward clinically favorable outcomes. We discuss future research directions that might further address the phage-resistance problem, to foster widespread development and deployment of therapeutic phage strategies that outsmart evolved bacterial resistance in clinical settings. | 2023 | 37268007 |
| 9192 | 5 | 0.9954 | Antimicrobial peptides: Sustainable application informed by evolutionary constraints. The proliferation and global expansion of multidrug-resistant (MDR) bacteria have deepened the need to develop novel antimicrobials. Antimicrobial peptides (AMPs) are regarded as promising antibacterial agents because of their broad-spectrum antibacterial activity and multifaceted mechanisms of action with non-specific targets. However, if AMPs are to be applied sustainably, knowledge of how they induce resistance in pathogenic bacteria must be mastered to avoid repeating the traditional antibiotic resistance mistakes currently faced. Furthermore, the evolutionary constraints on the acquisition of AMP resistance by microorganisms in the natural environment, such as functional compatibility and fitness trade-offs, inform the translational application of AMPs. Consequently, the shortcut to achieve sustainable utilization of AMPs is to uncover the evolutionary constraints of bacteria on AMP resistance in nature and find the tricks to exploit these constraints, such as applying AMP cocktails to minimize the efficacy of selection for resistance or combining nanomaterials to maximize the costs of AMP resistance. Altogether, this review dissects the benefits, challenges, and opportunities of utilizing AMPs against disease-causing bacteria, and highlights the use of AMP cocktails or nanomaterials to proactively address potential AMP resistance crises in the future. | 2022 | 35752270 |
| 9589 | 6 | 0.9954 | Phage Therapy: Going Temperate? Strictly lytic phages have been consensually preferred for phage therapy purposes. In contrast, temperate phages have been avoided due to an inherent capacity to mediate transfer of genes between bacteria by specialized transduction - an event that may increase bacterial virulence, for example, by promoting antibiotic resistance. Now, advances in sequencing technologies and synthetic biology are providing new opportunities to explore the use of temperate phages for therapy against bacterial infections. By doing so we can considerably expand our armamentarium against the escalating threat of antibiotic-resistant bacteria. | 2019 | 30466900 |
| 8265 | 7 | 0.9954 | Mathematical modelling of CRISPR-Cas system effects on biofilm formation. Clustered regularly interspaced short palindromic repeats (CRISPR), linked with CRISPR associated (Cas) genes, can confer adaptive immunity to bacteria, against bacteriophage infections. Thus from a therapeutic standpoint, CRISPR immunity increases biofilm resistance to phage therapy. Recently, however, CRISPR-Cas genes have been implicated in reducing biofilm formation in lysogenized cells. Thus CRISPR immunity can have complex effects on phage-host-lysogen interactions, particularly in a biofilm. In this contribution, we develop and analyse a series of dynamical systems to elucidate and disentangle these interactions. Two competition models are used to study the effects of lysogens (first model) and CRISPR-immune bacteria (second model) in the biofilm. In the third model, the effect of delivering lysogens to a CRISPR-immune biofilm is investigated. Using standard analyses of equilibria, stability and bifurcations, our models predict that lysogens may be able to displace CRISPR-immune bacteria in a biofilm, and thus suggest strategies to eliminate phage-resistant biofilms. | 2017 | 28426329 |
| 8350 | 8 | 0.9954 | A Physiological Basis for Nonheritable Antibiotic Resistance. Antibiotics constitute one of the cornerstones of modern medicine. However, individuals may succumb to a bacterial infection if a pathogen survives exposure to antibiotics. The ability of bacteria to survive bactericidal antibiotics results from genetic changes in the preexisting bacterial genome, from the acquisition of genes from other organisms, and from nonheritable phenomena that give rise to antibiotic tolerance. Nonheritable antibiotic tolerance can be exhibited by a large fraction of the bacterial population or by a small subpopulation referred to as persisters. Nonheritable resistance to antibiotics has been ascribed to the activity of toxins that are part of toxin-antitoxin modules, to the universal energy currency ATP, and to the signaling molecule guanosine (penta) tetraphosphate. However, these molecules are dispensable for nonheritable resistance to antibiotics in many organisms. By contrast, nutrient limitation, treatment with bacteriostatic antibiotics, or expression of genes that slow bacterial growth invariably promote nonheritable resistance. We posit that antibiotic persistence results from conditions promoting feedback inhibition among core cellular processes, resulting phenotypically in a slowdown or halt in bacterial growth. | 2020 | 32546621 |
| 9141 | 9 | 0.9954 | Metallic Nanoparticles-Friends or Foes in the Battle against Antibiotic-Resistant Bacteria? The rapid spread of antibiotic resistances among bacteria demands novel strategies for infection control, and metallic nanoparticles appear as promising tools because of their unique size and tunable properties that allow their antibacterial effects to be maximized. Furthermore, their diverse mechanisms of action towards multiple cell components have suggested that bacteria could not easily develop resistance against nanoparticles. However, research published over the last decade has proven that bacteria can indeed evolve stable resistance mechanisms upon continuous exposure to metallic nanoparticles. In this review, we summarize the currently known individual and collective strategies employed by bacteria to cope with metallic nanoparticles. Importantly, we also discuss the adverse side effects that bacterial exposure to nanoparticles may have on antibiotic resistance dissemination and that might constitute a challenge for the implementation of nanoparticles as antibacterial agents. Overall, studies discussed in this review point out that careful management of these very promising antimicrobials is necessary to preserve their efficacy for infection control. | 2021 | 33673231 |
| 9195 | 10 | 0.9954 | Complement-resistance mechanisms of bacteria. Despite more than a century of parallel research on bacteria and the complement system, relatively little is known of the mechanisms whereby pathogenic bacteria can escape complement-related opsonophagocytosis and direct killing. It is likely that pathogenicity in bacteria has arisen more accidentally than in viruses, and on the basis of selection from natural mutants rather than by outright stealing or copying of genetic codes from the host. In this review we will discuss complement resistance as one of the features that makes a bacterium a pathogen. | 1999 | 10816084 |
| 9178 | 11 | 0.9954 | Targeting non-multiplying organisms as a way to develop novel antimicrobials. Increasing resistance and decreasing numbers of antibiotics reaching the market point to a growing need for novel antibacterial drugs. Most antibiotics are very inefficient at killing non-multiplying bacteria, which live side by side with multiplying ones of the same strain in a clinical infection. Although non-multiplying bacteria do not usually cause disease, they can revert to the multiplying state that leads to overt disease, at which time resistance can emerge. Here we discuss the concept of developing antibacterial drugs by targeting non-multiplying organisms. We define non-multiplying bacteria, discuss the efficacy of existing antibiotics, and assess whether targeting these bacteria might lead to new antibiotics that will decrease the rate of emergence of resistance. Lastly, we review the potential of new molecular targets and live non-multiplying bacteria as possible routes for the development of novel antimicrobial drugs. | 2008 | 18262665 |
| 9182 | 12 | 0.9953 | Harnessing CRISPR/Cas9 in engineering biotic stress immunity in crops. There is significant potential for CRISPR/Cas9 to be used in developing crops that can adapt to biotic stresses such as fungal, bacterial, viral, and pest infections and weeds. The increasing global population and climate change present significant threats to food security by putting stress on plants, making them more vulnerable to diseases and productivity losses caused by pathogens, pests, and weeds. Traditional breeding methods are inadequate for the rapid development of new plant traits needed to counteract this decline in productivity. However, modern advances in genome-editing technologies, particularly CRISPR/Cas9, have transformed crop protection through precise and targeted modifications of plant genomes. This enables the creation of resilient crops with improved resistance to pathogens, pests, and weeds. This review examines various methods by which CRISPR/Cas9 can be utilized for crop protection. These methods include knocking out susceptibility genes, introducing resistance genes, and modulating defense genes. Potential applications of CRISPR/Cas9 in crop protection involve introducing genes that confer resistance to pathogens, disrupting insect genes responsible for survival and reproduction, and engineering crops that are resistant to herbicides. In conclusion, CRISPR/Cas9 holds great promise for advancing crop protection and ensuring food security in the face of environmental challenges and increasing population pressures. The most recent advancements in CRISPR technology for creating resistance to bacteria, fungi, viruses, and pests are covered here. We wrap up by outlining the most pressing issues and technological shortcomings, as well as unanswered questions for further study. | 2025 | 40663257 |
| 8328 | 13 | 0.9953 | The Diverse Impacts of Phage Morons on Bacterial Fitness and Virulence. The viruses that infect bacteria, known as phages, are the most abundant biological entity on earth. They play critical roles in controlling bacterial populations through phage-mediated killing, as well as through formation of bacterial lysogens. In this form, the survival of the phage depends on the survival of the bacterial host in which it resides. Thus, it is advantageous for phages to encode genes that contribute to bacterial fitness and expand the environmental niche. In many cases, these fitness factors also make the bacteria better able to survive in human infections and are thereby considered pathogenesis or virulence factors. The genes that encode these fitness factors, known as "morons," have been shown to increase bacterial fitness through a wide range of mechanisms and play important roles in bacterial diseases. This review outlines the benefits provided by phage morons in various aspects of bacterial life, including phage and antibiotic resistance, motility, adhesion and quorum sensing. | 2019 | 30635074 |
| 8334 | 14 | 0.9953 | Tumour progression: random mutations or an integrated survival response to cellular stress conserved from unicellular organisms? The current paradigm states that cancer progression is caused by random independent mutations, each selected for its survival advantages. The accelerated rates of phenotypic changes, the pleiotropic effect of several genes involved in progression--which need not be necessarily mutated for inducing the observed changes in cancer cell behaviour--lead us to propose an alternative hypothesis. Malignant progression might be a result of the unveiling of a cell-survival program, induced by various aggressions in the same way as the SOS system is induced and regulated in bacteria. This hypothesis depends on the homology between several genes involved in cancer progression (such as bcl2, mdm2, the mismatch repair genes, the heat shock protein genes, the pleiotropic resistance genes, the telomerase gene ...) and several genes involved in the survival of prokaryotes and eukaryotes under stress. The development of multicellular organisms could not take place without the building of a control program, exemplified by the so-called anti-oncogenes. However, this control program had to integrate some weaknesses, in order to allow for embryogenesis, growth, and wound healing. These weaknesses, neutral from an evolutionary point of view--since most cancers are sporadic and kill their hosts long after the birth of the offspring--are exploited by the survival program of individual cells, inherited from the genome of prokaryotes and unicellular eukaryotes, and repressed but not suppressed in animals. If this theory is true, it is probable that (i) no anti-oncogenes will be found in unicellular organisms, (ii) the sensitivity to mutations will be higher in genes involved in proliferation and in anti-oncogenes such as p53 and Rb, than in genes not involved in the cancer process, (iii) a process of transfer of genetic information exists in cancer cells as it exists in bacteria. The identification of the genes governing the survival program could lead to new therapeutic approaches. | 1996 | 8733476 |
| 8266 | 15 | 0.9952 | Remarkable Mechanisms in Microbes to Resist Phage Infections. Bacteriophages (phages) specifically infect bacteria and are the most abundant biological entities on Earth. The constant exposure to phage infection imposes a strong selective pressure on bacteria to develop viral resistance strategies that promote prokaryotic survival. Thus, this parasite-host relationship results in an evolutionary arms race of adaptation and counteradaptation between the interacting partners. The evolutionary outcome is a spectrum of remarkable strategies used by the bacteria and phages as they attempt to coexist. These approaches include adsorption inhibition, injection blocking, abortive infection, toxin-antitoxin, and CRISPR-Cas systems. In this review, we highlight the diverse and complementary antiphage systems in bacteria, as well as the evasion mechanisms used by phages to escape these resistance strategies. | 2014 | 26958724 |
| 9238 | 16 | 0.9952 | Sexual isolation and speciation in bacteria. Like organisms from all other walks of life, bacteria are capable of sexual recombination. However, unlike most plants and animals, bacteria recombine only rarely, and when they do they are extremely promiscuous in their choice of sexual partners. There may be no absolute constraints on the evolutionary distances that can be traversed through recombination in the bacterial world, but interspecies recombination is reduced by a variety of factors, including ecological isolation, behavioral isolation, obstacles to DNA entry, restriction endonuclease activity, resistance to integration of divergent DNA sequences, reversal of recombination by mismatch repair, and functional incompatibility of recombined segments. Typically, individual bacterial species are genetically variable for most of these factors. Therefore, natural selection can modulate levels of sexual isolation, to increase the transfer of genes useful to the recipient while minimizing the transfer of harmful genes. Interspecies recombination is optimized when recombination involves short segments that are just long enough to transfer an adaptation, without co-transferring potentially harmful DNA flanking the adaptation. Natural selection has apparently acted to reduce sexual isolation between bacterial species. Evolution of sexual isolation is not a milestone toward speciation in bacteria, since bacterial recombination is too rare to oppose adaptive divergence between incipient species. Ironically, recombination between incipient bacterial species may actually foster the speciation process, by prohibiting one incipient species from out-competing the other to extinction. Interspecific recombination may also foster speciation by introducing novel gene loci from divergent species, allowing invasion of new niches. | 2002 | 12555790 |
| 9580 | 17 | 0.9952 | Antibiotic resistance in bacterial communities. Bacteria are single-celled organisms, but the survival of microbial communities relies on complex dynamics at the molecular, cellular, and ecosystem scales. Antibiotic resistance, in particular, is not just a property of individual bacteria or even single-strain populations, but depends heavily on the community context. Collective community dynamics can lead to counterintuitive eco-evolutionary effects like survival of less resistant bacterial populations, slowing of resistance evolution, or population collapse, yet these surprising behaviors are often captured by simple mathematical models. In this review, we highlight recent progress - in many cases, advances driven by elegant combinations of quantitative experiments and theoretical models - in understanding how interactions between bacteria and with the environment affect antibiotic resistance, from single-species populations to multispecies communities embedded in an ecosystem. | 2023 | 37054512 |
| 9177 | 18 | 0.9952 | Multitarget Approaches against Multiresistant Superbugs. Despite efforts to develop new antibiotics, antibacterial resistance still develops too fast for drug discovery to keep pace. Often, resistance against a new drug develops even before it reaches the market. This continued resistance crisis has demonstrated that resistance to antibiotics with single protein targets develops too rapidly to be sustainable. Most successful long-established antibiotics target more than one molecule or possess targets, which are encoded by multiple genes. This realization has motivated a change in antibiotic development toward drug candidates with multiple targets. Some mechanisms of action presuppose multiple targets or at least multiple effects, such as targeting the cytoplasmic membrane or the carrier molecule bactoprenol phosphate and are therefore particularly promising. Moreover, combination therapy approaches are being developed to break antibiotic resistance or to sensitize bacteria to antibiotic action. In this Review, we provide an overview of antibacterial multitarget approaches and the mechanisms behind them. | 2020 | 32156116 |
| 9588 | 19 | 0.9952 | 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 |