# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 8237 | 0 | 1.0000 | Antibiotic tolerance, persistence, and resistance of the evolved minimal cell, Mycoplasma mycoides JCVI-Syn3B. Antibiotic resistance is a growing problem, but bacteria can evade antibiotic treatment via tolerance and persistence. Antibiotic persisters are a small subpopulation of bacteria that tolerate antibiotics due to a physiologically dormant state. Hence, persistence is considered a major contributor to the evolution of antibiotic-resistant and relapsing infections. Here, we used the synthetically developed minimal cell Mycoplasma mycoides JCVI-Syn3B to examine essential mechanisms of antibiotic survival. The minimal cell contains only 473 genes, and most genes are essential. Its reduced complexity helps to reveal hidden phenomenon and fundamental biological principles can be explored because of less redundancy and feedback between systems compared to natural cells. We found that Syn3B evolves antibiotic resistance to different types of antibiotics expeditiously. The minimal cell also tolerates and persists against multiple antibiotics. It contains a few already identified persister-related genes, although lacking many systems previously linked to persistence (e.g. toxin-antitoxin systems, ribosome hibernation genes). | 2021 | 33997676 |
| 9135 | 1 | 0.9992 | Multidrug Resistance Pumps as a Keystone of Bacterial Resistance. Antibiotic resistance is a global problem of modern medicine. A harbinger of the onset of the postantibiotic era is the complexity and high cost of developing new antibiotics as well as their inefficiency due to the rapidly developing resistance of bacteria. Multidrug resistance (MDR) pumps, involved in the formation of resistance to xenobiotics, the export of toxins, the maintenance of cellular homeostasis, and the formation of biofilms and persistent cells, are the keystone of bacterial protection against antibiotics. MDR pumps are the basis for the nonspecific protection of bacteria, while modification of the drug target, inactivation of the drug, and switching of the target or sequestration of the target is the second specific line of their protection. Thus, the nonspecific protection of bacteria formed by MDR pumps is a barrier that prevents the penetration of antibacterial substances into the cell, which is the main factor determining the resistance of bacteria. Understanding the mechanisms of MDR pumps and a balanced assessment of their contribution to total resistance, as well as to antibiotic sensitivity, will either seriously delay the onset of the postantibiotic era or prevent its onset in the foreseeable future. | 2022 | 36843647 |
| 9545 | 2 | 0.9992 | MDR Pumps as Crossroads of Resistance: Antibiotics and Bacteriophages. At present, antibiotic resistance represents a global problem in modern medicine. In the near future, humanity may face a situation where medicine will be powerless against resistant bacteria and a post-antibiotic era will come. The development of new antibiotics is either very expensive or ineffective due to rapidly developing bacterial resistance. The need to develop alternative approaches to the treatment of bacterial infections, such as phage therapy, is beyond doubt. The cornerstone of bacterial defense against antibiotics are multidrug resistance (MDR) pumps, which are involved in antibiotic resistance, toxin export, biofilm, and persister cell formation. MDR pumps are the primary non-specific defense of bacteria against antibiotics, while drug target modification, drug inactivation, target switching, and target sequestration are the second, specific line of their defense. All bacteria have MDR pumps, and bacteriophages have evolved along with them and use the bacteria's need for MDR pumps to bind and penetrate into bacterial cells. The study and understanding of the mechanisms of the pumps and their contribution to the overall resistance and to the sensitivity to bacteriophages will allow us to either seriously delay the onset of the post-antibiotic era or even prevent it altogether due to phage-antibiotic synergy. | 2022 | 35740141 |
| 9132 | 3 | 0.9992 | Antibiotic resistance: a survival strategy. Antibiotics are natural, semi-synthetic, or synthetic molecules that target the cell wall of bacteria, DNA replication, RNA transcription, or mRNA translation, the cellular machinery responsible for the synthesis of precursor molecules. Bacteria have evolved and adopted numerous strategies to counteract the action of antibiotics. Antibiotic resistance is intrinsic and an inherent characteristic of the microorganism. Intrinsic resistance is due to cell wall impermeability, efflux, biofilm formation, and the expression of genes mediating inactivating enzymes. Antibiotic resistance can also arise by the acquisition of extracellular DNA and is expressed phenotypically as efflux, modification or acquisition of target sites, and enzymatic inactivation of the antibiotic. Not only have bacteria acquired the mechanisms necessary to withstand the effects of antibiotics, they have also acquired elaborate mechanisms to mobilize and disseminate these successful strategies: plasmids, transposons, insertion sequences, and cassettes. Antibiotic resistance is a major worldwide clinical problem of public health concern because of the reduced efficacy caused by the various mechanisms of resistance. Global strategies are emerging to help address this critical problem. | 2005 | 16134477 |
| 9586 | 4 | 0.9992 | 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 |
| 777 | 5 | 0.9991 | Multiantibiotic resistance caused by active drug extrusion in Pseudomonas aeruginosa and other gram-negative bacteria. All living organisms have been exposed to noxious compounds throughout their long evolutionary history and those surviving have evolved to fabricate devices that detoxicate and extrude these life threatening substances. It is likely, therefore, that all viable organisms, from bacteria to mammals, are equipped with active extrusion machinery. When bacteria are attacked by antibiotics, they use these tactics to combat the drugs and to develop resistance. Drugs extrusion machinery in Gram-negative bacteria is complex, consisting of the inner membrane transporter which acts as an energy-dependent extrusion pump; a binding protein which presumably connect both membranes; and the outer membrane exit channel. The extrusion pump assemblies are often encoded by chromosomal genes and might be expressed by mutation(s) or induced in the presence of drug(s). | 1997 | 9353746 |
| 9598 | 6 | 0.9991 | Strategies and molecular tools to fight antimicrobial resistance: resistome, transcriptome, and antimicrobial peptides. The increasing number of antibiotic resistant bacteria motivates prospective research toward discovery of new antimicrobial active substances. There are, however, controversies concerning the cost-effectiveness of such research with regards to the description of new substances with novel cellular interactions, or description of new uses of existing substances to overcome resistance. Although examination of bacteria isolated from remote locations with limited exposure to humans has revealed an absence of antibiotic resistance genes, it is accepted that these genes were both abundant and diverse in ancient living organisms, as detected in DNA recovered from Pleistocene deposits (30,000 years ago). Indeed, even before the first clinical use of antibiotics more than 60 years ago, resistant organisms had been isolated. Bacteria can exhibit different strategies for resistance against antibiotics. New genetic information may lead to the modification of protein structure affecting the antibiotic carriage into the cell, enzymatic inactivation of drugs, or even modification of cellular structure interfering in the drug-bacteria interaction. There are still plenty of new genes out there in the environment that can be appropriated by putative pathogenic bacteria to resist antimicrobial agents. On the other hand, there are several natural compounds with antibiotic activity that may be used to oppose them. Antimicrobial peptides (AMPs) are molecules which are wide-spread in all forms of life, from multi-cellular organisms to bacterial cells used to interfere with microbial growth. Several AMPs have been shown to be effective against multi-drug resistant bacteria and have low propensity to resistance development, probably due to their unique mode of action, different from well-known antimicrobial drugs. These substances may interact in different ways with bacterial cell membrane, protein synthesis, protein modulation, and protein folding. The analysis of bacterial transcriptome may contribute to the understanding of microbial strategies under different environmental stresses and allows the understanding of their interaction with novel AMPs. | 2013 | 24427156 |
| 9512 | 7 | 0.9991 | RND multidrug efflux pumps: what are they good for? Multidrug efflux pumps are chromosomally encoded genetic elements capable of mediating resistance to toxic compounds in several life forms. In bacteria, these elements are involved in intrinsic and acquired resistance to antibiotics. Unlike other well-known horizontally acquired antibiotic resistance determinants, genes encoding for multidrug efflux pumps belong to the core of bacterial genomes and thus have evolved over millions of years. The selective pressure stemming from the use of antibiotics to treat bacterial infections is relatively recent in evolutionary terms. Therefore, it is unlikely that these elements have evolved in response to antibiotics. In the last years, several studies have identified numerous functions for efflux pumps that go beyond antibiotic extrusion. In this review we present some examples of these functions that range from bacterial interactions with plant or animal hosts, to the detoxification of metabolic intermediates or the maintenance of cellular homeostasis. | 2013 | 23386844 |
| 9421 | 8 | 0.9991 | The neglected intrinsic resistome of bacterial pathogens. Bacteria with intrinsic resistance to antibiotics are a worrisome health problem. It is widely believed that intrinsic antibiotic resistance of bacterial pathogens is mainly the consequence of cellular impermeability and activity of efflux pumps. However, the analysis of transposon-tagged Pseudomonas aeruginosa mutants presented in this article shows that this phenotype emerges from the action of numerous proteins from all functional categories. Mutations in some genes make P. aeruginosa more susceptible to antibiotics and thereby represent new targets. Mutations in other genes make P. aeruginosa more resistant and therefore define novel mechanisms for mutation-driven acquisition of antibiotic resistance, opening a new research field based in the prediction of resistance before it emerges in clinical environments. Antibiotics are not just weapons against bacterial competitors, but also natural signalling molecules. Our results demonstrate that antibiotic resistance genes are not merely protective shields and offer a more comprehensive view of the role of antibiotic resistance genes in the clinic and in nature. | 2008 | 18286176 |
| 9133 | 9 | 0.9991 | Overcoming antimicrobial resistance by targeting resistance mechanisms. Three mechanisms of antimicrobial resistance predominate in bacteria: antibiotic inactivation, target site modification, and altered uptake by way of restricted entry and/or enhanced efflux. Many of these involve enzymes or transport proteins whose activity can be targeted directly in an attemptto compromise resistance and, thus, potentiate antimicrobial activity. Alternatively, novel agents unaffected by these resistance mechanisms can be developed. Given the ongoing challenge posed by antimicrobial resistance in bacteria, targeting resistance in this way may be our best hope at prolonging the antibiotic era. | 2001 | 11291743 |
| 9587 | 10 | 0.9991 | Antibacterial particles and predatory bacteria as alternatives to antibacterial chemicals in the era of antibiotic resistance. This review is focused on the subset of antibacterial agents whose action involves one-on-one targeting of infecting bacteria. These agents target individual bacteria and their efficacy is based on particle numbers in contrast to chemical agents such as antibiotics, whose efficacy is based on minimal inhibitory concentrations. Four extant members of this class are predatory bacteria, functional (plaque-forming) phages, and engineered particulate systems, phagemids (plasmids that contain a phage packaging signal) and antibacterial drones (ABDs) that package chromosomal island DNA carrying antibacterial genes. We differentiate the natural predators, phages and predatory bacteria, from the engineered delivery vehicles, phagemids and ABDs, because the latter are much more versatile and can largely bypass the historical warfare that informs the predator-prey interactions. | 2021 | 34688038 |
| 4273 | 11 | 0.9991 | Mathematical modeling on bacterial resistance to multiple antibiotics caused by spontaneous mutations. We formulate a mathematical model that describes the population dynamics of bacteria exposed to multiple antibiotics simultaneously, assuming that acquisition of resistance is through mutations due to antibiotic exposure. Qualitative analysis reveals the existence of a free-bacteria equilibrium, resistant-bacteria equilibrium and an endemic equilibrium where both bacteria coexist. | 2014 | 24467935 |
| 9130 | 12 | 0.9991 | 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 |
| 9490 | 13 | 0.9991 | 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 |
| 9241 | 14 | 0.9991 | 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 |
| 9356 | 15 | 0.9991 | The expression of antibiotic resistance genes in antibiotic-producing bacteria. Antibiotic-producing bacteria encode antibiotic resistance genes that protect them from the biologically active molecules that they produce. The expression of these genes needs to occur in a timely manner: either in advance of or concomitantly with biosynthesis. It appears that there have been at least two general solutions to this problem. In many cases, the expression of resistance genes is tightly linked to that of antibiotic biosynthetic genes. In others, the resistance genes can be induced by their cognate antibiotics or by intermediate molecules from their biosynthetic pathways. The regulatory mechanisms that couple resistance to antibiotic biosynthesis are mechanistically diverse and potentially relevant to the origins of clinical antibiotic resistance. | 2014 | 24964724 |
| 9541 | 16 | 0.9991 | The Role of the Hfq Protein in Bacterial Resistance to Antibiotics: A Narrative Review. The antibiotic resistance of pathogenic microorganisms is currently one of most major medical problems, causing a few million deaths every year worldwide due to untreatable bacterial infections. Unfortunately, the prognosis is even worse, as over 8 million deaths associated with antibiotic resistance are expected to occur in 2050 if no new effective antibacterial treatments are discovered. The Hfq protein has been discovered as a bacterial RNA chaperone. However, subsequent studies have indicated that this small protein (composed of 102 amino acid residues in Escherichia coli) has more activities, including binding to DNA and influencing its compaction, interaction with biological membranes, formation of amyloid-like structures, and others. Although Hfq is known to participate in many cellular processes, perhaps surprisingly, only reports from recent years have demonstrated its role in bacterial antibiotic resistance. The aim of this narrative review is to discuss how can Hfq affects antibiotic resistance in bacteria and propose how this knowledge may facilitate developing new therapeutic strategies against pathogenic bacteria. We indicate that the mechanisms by which the Hfq protein modulates the response of bacterial cells to antibiotics are quite different, from the regulation of the expression of genes coding for proteins directly involved in antibiotic transportation or action, through direct effects on membranes, to controlling the replication or transposition of mobile genetic elements bearing antibiotic resistance genes. Therefore, we suggest that Hfq could be considered a potential target for novel antimicrobial compounds. We also discuss difficulties in developing such drugs, but since Hfq appears to be a promising target for drugs that may enhance the efficacy of antibiotics, we propose that works on such potential therapeutics are encouraged. | 2025 | 40005731 |
| 9420 | 17 | 0.9991 | The intrinsic resistance of bacteria. Antibiotic resistance is often considered to be a trait acquired by previously susceptible bacteria, on the basis of which can be attributed to the horizontal acquisition of new genes or the occurrence of spontaneous mutation. In addition to acquired resistance, bacteria have a trait of intrinsic resistance to different classes of antibiotics. An intrinsic resistance gene is involved in intrinsic resistance, and its presence in bacterial strains is independent of previous antibiotic exposure and is not caused by horizontal gene transfer. Recently, interest in intrinsic resistance genes has increased, because these gene products not only may provide attractive therapeutic targets for development of novel drugs that rejuvenate the activity of existing antibiotics, and but also might predict future emergence of resistant pathogens if they become mobilized. In the present review, we summarize the conventional examples of intrinsic resistance, including the impermeability of cellular envelopes, the activity of multidrug efflux pumps or lack of drug targets. We also demonstrate that transferases and enzymes involved in basic bacterial metabolic processes confer intrinsic resistance in Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. We present as well information on the cryptic intrinsic resistance genes that do not confer resistance to their native hosts but are capable of conferring resistance when their expression levels are increased and the activation of the cryptic genes. Finally, we discuss that intrinsic genes could be the origin of acquired resistance, especially in the genus Acinetobacter. | 2016 | 27806928 |
| 4433 | 18 | 0.9991 | The Vancomycin Group of Antibiotics and the Fight against Resistant Bacteria. A last line of defence against "superbugs" are the vancomycin group antibiotics. This review describes the determination of their mode of action, and a mechanism of resistance to them. Remarkably, this mechanism of resistance can be overcome without directly modifying the binding site of the antibiotics for the cell-wall precursors of pathogenic bacteria. | 1999 | 29711719 |
| 9419 | 19 | 0.9991 | Genes required for mycobacterial growth defined by high density mutagenesis. Despite over a century of research, tuberculosis remains a leading cause of infectious death worldwide. Faced with increasing rates of drug resistance, the identification of genes that are required for the growth of this organism should provide new targets for the design of antimycobacterial agents. Here, we describe the use of transposon site hybridization (TraSH) to comprehensively identify the genes required by the causative agent, Mycobacterium tuberculosis, for optimal growth. These genes include those that can be assigned to essential pathways as well as many of unknown function. The genes important for the growth of M. tuberculosis are largely conserved in the degenerate genome of the leprosy bacillus, Mycobacterium leprae, indicating that non-essential functions have been selectively lost since this bacterium diverged from other mycobacteria. In contrast, a surprisingly high proportion of these genes lack identifiable orthologues in other bacteria, suggesting that the minimal gene set required for survival varies greatly between organisms with different evolutionary histories. | 2003 | 12657046 |