# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 9088 | 0 | 0.9865 | Cocrystallizing and Codelivering Complementary Drugs to Multidrugresistant Tuberculosis Bacteria in Perfecting Multidrug Therapy. Bacteria cells exhibit multidrug resistance in one of two ways: by raising the genetic expression of multidrug efflux pumps or by accumulating several drug-resistant components in many genes. Multidrug-resistive tuberculosis bacteria are treated by multidrug therapy, where a few certain antibacterial drugs are administered together to kill a bacterium jointly. A major drawback of conventional multidrug therapy is that the administration never ensures the reaching of different drug molecules to a particular bacterium cell at the same time, which promotes growing drug resistivity step-wise. As a result, it enhances the treatment time. With additional tabletability and plasticity, the formation of a cocrystal of multidrug can ensure administrating the multidrug chemically together to a target bacterium cell. With properly maintaining the basic philosophy of multidrug therapy here, the synergistic effects of drug molecules can ensure killing the bacteria, even before getting the option to raise the drug resistance against them. This can minimize the treatment span, expenditure and drug resistance. A potential threat of epidemic from tuberculosis has appeared after the Covid-19 outbreak. An unwanted loop of finding molecules with the potential to kill tuberculosis, getting their corresponding drug approvals, and abandoning the drug after facing drug resistance can be suppressed here. This perspective aims to develop the universal drug regimen by postulating the principles of drug molecule selection, cocrystallization, and subsequent harmonisation within a short period to address multidrug-resistant bacteria. | 2023 | 37150990 |
| 9177 | 1 | 0.9865 | 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 |
| 8350 | 2 | 0.9864 | 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 |
| 9174 | 3 | 0.9863 | 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 |
| 8424 | 4 | 0.9862 | Postseptational chromosome partitioning in bacteria. Mutations in the spoIIIE gene prevent proper partitioning of one chromosome into the developing prespore during sporulation but have no overt effect on partitioning in vegetatively dividing cells. However, the expression of spoIIIE in vegetative cells and the occurrence of genes closely related to spoIIIE in a range of nonsporulating eubacteria suggested a more general function for the protein. Here we show that SpoIIIE protein is needed for optimal chromosome partitioning in vegetative cells of Bacillus subtilis when the normal tight coordination between septation and nucleoid partitioning is perturbed or when septum positioning is altered. A functional SpoIIIE protein allows cells to recover from a state in which their chromosome has been trapped by a closing septum. By analogy to its function during sporulation, we suggest that SpoIIIE facilitates partitioning by actively translocating the chromosome out of the septum. In addition to enhancing the fidelity of nucleoid partitioning, SpoIIIE also seems to be required for maximal resistance to antibiotics that interfere with DNA metabolism. The results have important implications for our understanding of the functions of genes involved in the primary partitioning machinery in bacteria and of how septum placement is controlled. | 1995 | 7567988 |
| 9108 | 5 | 0.9862 | Learning from losers. Bacteria can overcome environmental challenges by killing nearby bacteria and incorporating their DNA. | 2017 | 29148975 |
| 9376 | 6 | 0.9861 | Historical Contingency Drives Compensatory Evolution and Rare Reversal of Phage Resistance. Bacteria and lytic viruses (phages) engage in highly dynamic coevolutionary interactions over time, yet we have little idea of how transient selection by phages might shape the future evolutionary trajectories of their host populations. To explore this question, we generated genetically diverse phage-resistant mutants of the bacterium Pseudomonas syringae. We subjected the panel of mutants to prolonged experimental evolution in the absence of phages. Some populations re-evolved phage sensitivity, whereas others acquired compensatory mutations that reduced the costs of resistance without altering resistance levels. To ask whether these outcomes were driven by the initial genetic mechanisms of resistance, we next evolved independent replicates of each individual mutant in the absence of phages. We found a strong signature of historical contingency: some mutations were highly reversible across replicate populations, whereas others were highly entrenched. Through whole-genome sequencing of bacteria over time, we also found that populations with the same resistance gene acquired more parallel sets of mutations than populations with different resistance genes, suggesting that compensatory adaptation is also contingent on how resistance initially evolved. Our study identifies an evolutionary ratchet in bacteria-phage coevolution and may explain previous observations that resistance persists over time in some bacterial populations but is lost in others. We add to a growing body of work describing the key role of phages in the ecological and evolutionary dynamics of their host communities. Beyond this specific trait, our study provides a new insight into the genetic architecture of historical contingency, a crucial component of interpreting and predicting evolution. | 2022 | 35994371 |
| 9173 | 7 | 0.9861 | 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 |
| 9371 | 8 | 0.9861 | Coevolutionary history of predation constrains the evolvability of antibiotic resistance in prey bacteria. Understanding how the historical contingency of biotic interactions shapes the evolvability of bacterial populations is imperative for the predictability of the eco-evolutionary dynamics of microbial communities. While microbial predators like Myxococcus xanthus influence the frequency of antibiotic-resistant bacteria in nature, the effect of adaptation to the presence of predators on the evolvability of prey bacteria to future stressors is unclear. Hence, to understand the influence of the coevolutionary history of predation on the evolvability of antibiotic resistance, we propagated variants of E. coli, pre-adapted to distinct biotic and abiotic conditions, in gradually increasing concentrations of antibiotics. We show that pre-adaptation to predators limits the evolution of a high degree of antibiotic resistance. Moreover, lower degree of resistance in the evolved strains also incurs reduced fitness costs while preserving their ancestral ability to resist predation. Together, we demonstrate that the history of biotic interactions can strongly influence the evolvability of bacteria. | 2025 | 40461734 |
| 9238 | 9 | 0.9860 | 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 |
| 9589 | 10 | 0.9860 | 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 |
| 8425 | 11 | 0.9860 | Carotenoid biosynthesis in extremophilic Deinococcus-Thermus bacteria. Bacteria from the phylum Deinococcus-Thermus are known for their resistance to extreme stresses including radiation, oxidation, desiccation and high temperature. Cultured Deinococcus-Thermus bacteria are usually red or yellow pigmented because of their ability to synthesize carotenoids. Unique carotenoids found in these bacteria include deinoxanthin from Deinococcus radiodurans and thermozeaxanthins from Thermus thermophilus. Investigations of carotenogenesis will help to understand cellular stress resistance of Deinococcus-Thermus bacteria. Here, we discuss the recent progress toward identifying carotenoids, carotenoid biosynthetic enzymes and pathways in some species of Deinococcus-Thermus extremophiles. In addition, we also discuss the roles of carotenoids in these extreme bacteria. | 2010 | 20832321 |
| 8264 | 12 | 0.9860 | 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 |
| 9366 | 13 | 0.9860 | Impact of bacterial mutation rate on coevolutionary dynamics between bacteria and phages. Mutator bacteria are frequently found in natural populations of bacteria and although coevolution with parasitic viruses (phages) is thought to be one reason for their persistence, it remains unclear how the presence of mutators affects coevolutionary dynamics. We hypothesized that phages must themselves adapt more rapidly or go extinct, in the face of rapidly evolving mutator bacteria. We compared the coevolutionary dynamics of wild-type Pseudomonas fluorescens SBW25 with a lytic phage to the dynamics of an isogenic mutator of P. fluorescens SBW25 together with the same phage. At the beginning of the experiment both wild-type bacteria and mutator bacteria coevolved with phages. However, mutators rapidly evolved higher levels of sympatric resistance to phages. The phages were unable to "keep-up" with the mutator bacteria, and these rates of coevolution declined to less than the rates of coevolution between the phages and wild-type bacteria. By the end of the experiment, the sympatric resistance of the mutator bacteria was not significantly different to the sympatric resistance of the wild-type bacteria. This suggests that the importance of mutators in the coevolutionary interactions with a particular phage population is likely to be short-lived. More generally, the results demonstrate that coevolving enemies may escape from Red-Queen dynamics. | 2010 | 20497216 |
| 8183 | 14 | 0.9860 | Modification of arthropod vector competence via symbiotic bacteria. Some of the world's most devastating diseases are transmitted by arthropod vectors. Attempts to control these arthropods are currently being challenged by the widespread appearance of insecticide resistance. It is therefore desirable to develop alternative strategies to complement existing methods of vector control. In this review, Charles Beard, Scott O'Neill, Robert Tesh, Frank Richards and Serap Aksoy present an approach for introducing foreign genes into insects in order to confer refractoriness to vector populations, ie. the inability to transmit disease-causing agents. This approach aims to express foreign anti-parasitic or anti-viral gene products in symbiotic bacteria harbored by insects. The potential use of naturally occurring symbiont-based mechanisms in the spread of such refractory phenotypes is also discussed. | 1993 | 15463748 |
| 8267 | 15 | 0.9860 | 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 |
| 8161 | 16 | 0.9859 | Integrative strategies against multidrug-resistant bacteria: Synthesizing novel antimicrobial frontiers for global health. Concerningly, multidrug-resistant bacteria have emerged as a prime worldwide trouble, obstructing the treatment of infectious diseases and causing doubts about the therapeutic accidentalness of presently existing drugs. Novel antimicrobial interventions deserve development as conventional antibiotics are incapable of keeping pace with bacteria evolution. Various promising approaches to combat MDR infections are discussed in this review. Antimicrobial peptides are examined for their broad-spectrum efficacy and reduced ability to develop resistance, while phage therapy may be used under extreme situations when antibiotics fail. In addition, the possibility of CRISPR-Cas systems for specifically targeting and eradicating resistance genes from bacterial populations will be explored. Nanotechnology has opened up the route to improve the delivery system of the drug itself, increasing the efficacy and specificity of antimicrobial action while protecting its host. Discovering potential antimicrobial agents is an exciting prospect through developments in synthetic biology and the rediscovery of natural product-based medicines. Moreover, host-directed therapies are now becoming popular as an adjunct to the main strategies of therapeutics without specifically targeting pathogens. Although these developments appear impressive, questions about production scaling, regulatory approvals, safety, and efficacy for clinical employment still loom large. Thus, tackling the MDR burden requires a multi-pronged plan, integrating newer treatment modalities with existing antibiotic regimens, enforcing robust stewardship initiatives, and effecting policy changes at the global level. The international health community can gird itself against the growing menace of antibiotic resistance if collaboration between interdisciplinary bodies and sustained research endeavours is encouraged. In this study, we evaluate the synergistic potential of combining various medicines in addition to summarizing recent advancements. To rethink antimicrobial stewardship in the future, we provide a multi-tiered paradigm that combines pathogen-focused and host-directed strategies. | 2025 | 40914328 |
| 9210 | 17 | 0.9859 | Plasmid maintenance systems suitable for GMO-based bacterial vaccines. Live carrier-based bacterial vaccines represent a vaccine strategy that offers exceptional flexibility. Commensal or attenuated strains of pathogenic bacteria can be used as live carriers to present foreign antigens from unrelated pathogens to the immune system, with the aim of eliciting protective immune responses. As for oral immunisation, such an approach obviates the usual loss of antigen integrity observed during gastrointestinal passage and allows the delivery of a sufficient antigen dose to the mucosal immune system. Antibiotic and antibiotic-resistance genes have traditionally been used for the maintenance of recombinant plasmid vectors in bacteria used for biotechnological purposes. However, their continued use may appear undesirable in the field of live carrier-based vaccine development. This review focuses on strategies to omit antibiotic resistance determinants in live bacterial vaccines and discusses several balanced lethal-plasmid stabilisation systems with respect to maintenance of plasmid inheritance and antigenicity of plasmid-encoded antigen in vivo. | 2005 | 15755571 |
| 8139 | 18 | 0.9859 | TAL effectors: highly adaptable phytobacterial virulence factors and readily engineered DNA-targeting proteins. Transcription activator-like (TAL) effectors are transcription factors injected into plant cells by pathogenic bacteria of the genus Xanthomonas. They function as virulence factors by activating host genes important for disease, or as avirulence factors by turning on genes that provide resistance. DNA-binding specificity is encoded by polymorphic repeats in each protein that correspond one-to-one with different nucleotides. This code has facilitated target identification and opened new avenues for engineering disease resistance. It has also enabled TAL effector customization for targeted gene control, genome editing, and other applications. This article reviews the structural basis for TAL effector-DNA specificity, the impact of the TAL effector-DNA code on plant pathology and engineered resistance, and recent accomplishments and future challenges in TAL effector-based DNA targeting. | 2013 | 23707478 |
| 9584 | 19 | 0.9859 | Using bacteria to express and display anti-parasite molecules in mosquitoes: current and future strategies. Vector-borne diseases impose enormous health and economical burdens throughout the world. Unfortunately, as insecticide and drug resistance spread, these burdens will increase unless new control measures are developed. Genetically modifying vectors to be incapable of transmitting parasites is one possible control strategy and much progress has been made towards this goal. Numerous effector molecules have been identified that interfere with parasite development in its insect vectors, and techniques for transforming the vectors with genes encoding these molecules have been established. While the ability to generate refractory vectors is close at hand, a mechanism for replacing a wild vector population with a refractory one remains elusive. This review examines the feasibility of using bacteria to deliver the anti-parasitic effector molecules to wild vector populations. The first half briefly examines paratransgenic approaches currently being tested in both the triatomine bug and tsetse fly. The second half explores the possibility of using midgut bacteria to control malaria transmission by Anopheles mosquitoes. | 2005 | 15894187 |