# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 9058 | 0 | 1.0000 | Antisense Agents against Antibiotic-resistant Bacteria. The dramatically increasing levels of antibiotic resistance are being seen worldwide and are a significant threat to public health. Antibiotic and drug resistance is seen in various bacterial species. Antibiotic resistance is associated with increased morbidity and mortality and increased treatment costs. Antisense-related technologies include oligonucleotides that interfere with gene transcription and expression; these oligonucleotides can help treat antibiotic-resistant bacteria. The important oligonucleotides include Peptide Nucleic Acids (PNAs), Phosphorodiamidate Morpholino Oligomers (PPMOs), and Locked Nucleic Acids (LNAs). Typically, the size of these structures (oligonucleotides) is 10 to 20 bases. PNAs, PPMOs, and LNAs are highlighted in this review as targets for genes that cause the gene to be destroyed and impede bacterial growth. These results open a new perspective for therapeutic intervention. Future studies need to examine different aspects of antisense agents, such as the safety, toxicity, and pharmacokinetic properties of antisense agents in clinical treatment. | 2022 | 35034590 |
| 9814 | 1 | 0.9994 | Antisense antimicrobial therapeutics. Antisense antimicrobial therapeutics are synthetic oligomers that silence expression of specific genes. This specificity confers an advantage over broad-spectrum antibiotics by avoiding unintended effects on commensal bacteria. The sequence-specificity and short length of antisense antimicrobials also pose little risk to human gene expression. Because antisense antimicrobials are a platform technology, they can be rapidly designed and synthesized to target almost any microbe. This reduces drug discovery time, and provides flexibility and a rational approach to drug development. Recent work has shown that antisense technology has the potential to address the antibiotic-resistance crisis, since resistance mechanisms for standard antibiotics apparently have no effect on antisense antimicrobials. Here, we describe current reports of antisense antimicrobials targeted against viruses, parasites, and bacteria. | 2016 | 27375107 |
| 9528 | 2 | 0.9993 | Polycarbonates with Potent and Selective Antimicrobial Activity toward Gram-Positive Bacteria. The resistance developed by life-threatening bacteria toward conventional antibiotics has become a major concern in public health. To combat antibiotic resistance, there has been a significant interest in the development of antimicrobial cationic polymers due to the ease of synthesis and low manufacturing cost compared to host-defense peptides (HDPs). Herein, we report the design and synthesis of amphiphilic polycarbonates containing primary amino groups. These polymers exhibit potent antimicrobial activity and excellent selectivity to Gram-positive bacteria, including multidrug resistant pathogens. Fluorescence and TEM studies suggest that these polymers are likely to kill bacteria by disrupting bacterial membranes. These polymers also show low tendency to elicit resistance in bacteria. Their further development may lead to new antimicrobial agents combating drug-resistance. | 2017 | 28064500 |
| 9546 | 3 | 0.9993 | Challenge in the Discovery of New Drugs: Antimicrobial Peptides against WHO-List of Critical and High-Priority Bacteria. Bacterial resistance has intensified in recent years due to the uncontrolled use of conventional drugs, and new bacterial strains with multiple resistance have been reported. This problem may be solved by using antimicrobial peptides (AMPs), which fulfill their bactericidal activity without developing much bacterial resistance. The rapid interaction between AMPs and the bacterial cell membrane means that the bacteria cannot easily develop resistance mechanisms. In addition, various drugs for clinical use have lost their effect as a conventional treatment; however, the synergistic effect of AMPs with these drugs would help to reactivate and enhance antimicrobial activity. Their efficiency against multi-resistant and extensively resistant bacteria has positioned them as promising molecules to replace or improve conventional drugs. In this review, we examined the importance of antimicrobial peptides and their successful activity against critical and high-priority bacteria published in the WHO list. | 2021 | 34064302 |
| 9446 | 4 | 0.9993 | Newer antibiotics for the treatment of respiratory tract infections. PURPOSE OF REVIEW: In this review, we highlight some of the developments achieved over the past 2 years in the field of novel antimicrobial compounds. RECENT FINDINGS: Modification of existing compound classes to create more powerful compounds capable of overcoming pathogen resistance and the introduction of completely new classes of antibiotics and inhibitors of new bacterial targets or inhibitors of genes relating to virulence or pathogenesis are the strategies more commonly employed in pharmacologic research. Ketolides, oxazolidinones, streptogramins, glycylcyclines, and peptide deformylase inhibitors are among the most promising classes of antibiotics. Recently, several lines of research have documented that it is effective to target the infection process rather than killing bacteria. This is important because it is likely that such a therapeutic strategy could ablate infection without inducing resistance. SUMMARY: Emergence of resistance to the antibiotics currently employed in clinical practice is a continual stimulus for further research aimed at identifying novel antimicrobial compounds. These drugs will perhaps effectively fight against bacteria that now are scarcely controlled by the traditional antimicrobial agents. Health care personnel must appreciate that only judicious use of antimicrobial drugs will prevent the further uncontrolled spread of bacterial resistance. Implementation of reference guidelines would probably be an effective way to limit antibiotic misuse. | 2004 | 15071370 |
| 9543 | 5 | 0.9993 | Antisense RNA regulation and application in the development of novel antibiotics to combat multidrug resistant bacteria. Despite the availability of antibiotics and vaccines, infectious diseases remain one of most dangerous threats to humans and animals. The overuse and misuse of antibacterial agents have led to the emergence of multidrug resistant bacterial pathogens. Bacterial cells are often resilient enough to survive in even the most extreme environments. To do so, the organisms have evolved different mechanisms, including a variety of two-component signal transduction systems, which allow the bacteria to sense the surrounding environment and regulate gene expression in order to adapt and respond to environmental stimuli. In addition, some bacteria evolve resistance to antibacterial agents while many bacterial cells are able to acquire resistance genes from other bacterial species to enable them to survive in the presence of toxic antimicrobial agents. The crisis of antimicrobial resistance is an unremitting menace to human health and a burden on public health. The rapid increase in antimicrobial resistant organisms and limited options for development of new classes of antibiotics heighten the urgent need to develop novel potent antibacterial therapeutics in order to combat multidrug resistant infections. In this review, we introduce the regulatory mechanisms of antisense RNA and significant applications of regulated antisense RNA interference technology in early drug discovery. This includes the identification and evaluation of drug targets in vitro and in vivo, the determination of mode of action for antibiotics and new antibacterial agents, as well as the development of peptide-nucleic acid conjugates as novel antibacterials. | 2013 | 23738437 |
| 8851 | 6 | 0.9992 | Sequence-Specific Targeting of Bacterial Resistance Genes Increases Antibiotic Efficacy. The lack of effective and well-tolerated therapies against antibiotic-resistant bacteria is a global public health problem leading to prolonged treatment and increased mortality. To improve the efficacy of existing antibiotic compounds, we introduce a new method for strategically inducing antibiotic hypersensitivity in pathogenic bacteria. Following the systematic verification that the AcrAB-TolC efflux system is one of the major determinants of the intrinsic antibiotic resistance levels in Escherichia coli, we have developed a short antisense oligomer designed to inhibit the expression of acrA and increase antibiotic susceptibility in E. coli. By employing this strategy, we can inhibit E. coli growth using 2- to 40-fold lower antibiotic doses, depending on the antibiotic compound utilized. The sensitizing effect of the antisense oligomer is highly specific to the targeted gene's sequence, which is conserved in several bacterial genera, and the oligomer does not have any detectable toxicity against human cells. Finally, we demonstrate that antisense oligomers improve the efficacy of antibiotic combinations, allowing the combined use of even antagonistic antibiotic pairs that are typically not favored due to their reduced activities. | 2016 | 27631336 |
| 9476 | 7 | 0.9992 | Phage design and directed evolution to evolve phage for therapy. Phage therapy or Phage treatment is the use of bacteriolysing phage in treating bacterial infections by using the viruses that infects and kills bacteria. This technique has been studied and practiced very long ago, but with the advent of antibiotics, it has been neglected. This foregone technique is now witnessing a revival due to development of bacterial resistance. Nowadays, with the awareness of genetic sequence of organisms, it is required that informed choices of phages have to be made for the most efficacious results. Furthermore, phages with the evolving genes are taken into consideration for the subsequent improvement in treating the patients for bacterial diseases. In addition, direct evolution methods are increasingly developing, since these are capable of creating new biological molecules having changed or unique activities, such as, improved target specificity, evolution of novel proteins with new catalytic properties or creation of nucleic acids that are capable of recognizing required pathogenic bacteria. This system is incorporates continuous evolution such as protein or genes are put under continuous evolution by providing continuous mutagenesis with least human intervention. Although, this system providing continuous directed evolution is very effective, it imposes some challenges due to requirement of heavy investment of time and resources. This chapter focuses on development of phage as a therapeutic agent against various bacteria causing diseases and it improvement using direct evolution of proteins and nucleic acids such that they target specific organisms. | 2023 | 37739551 |
| 9127 | 8 | 0.9992 | Antimicrobial Peptides: Virulence and Resistance Modulation in Gram-Negative Bacteria. Growing resistance to antibiotics is one of the biggest threats to human health. One of the possibilities to overcome this resistance is to use and develop alternative molecules such as antimicrobial peptides (AMPs). However, an increasing number of studies have shown that bacterial resistance to AMPs does exist. Since AMPs are immunity molecules, it is important to ensure that their potential therapeutic use is not harmful in the long term. Recently, several studies have focused on the adaptation of Gram-negative bacteria to subinhibitory concentrations of AMPs. Such concentrations are commonly found in vivo and in the environment. It is therefore necessary to understand how bacteria detect and respond to low concentrations of AMPs. This review focuses on recent findings regarding the impact of subinhibitory concentrations of AMPs on the modulation of virulence and resistance in Gram-negative bacteria. | 2020 | 32092866 |
| 9562 | 9 | 0.9992 | Fight against antimicrobial resistance. Antimicrobial and antibiotic resistance is ever increasing and the fight against it is a battle that can never be won. Nevertheless, some possibilities exist to improve this situation, at least in part. The present review article discusses some approaches that can be used to control microbial resistance. Possible strategies are (1) designing new vaccines against resistant bacterial strains; (2) investigation of the potential of both traditional and non-traditional sources of natural substances for use as new antibiotics; (3) search for genes specifying biosynthesis of antibiotics; (4) use of forgotten natural compounds and their transformation, and (5) investigation of new antibiotic targets in pathogenic bacteria. Particular attention is paid to the search for new compounds that would be able to inhibit pathogenic bacteria resistant to existing antibiotics. | 2018 | 30126284 |
| 9547 | 10 | 0.9992 | Confronting antibiotic-resistant pathogens: Distinctive drug delivery potentials of progressive nanoparticles. Antimicrobial resistance arises over time, usually due to genetic modifications. Global observations of high resistance rates to popular antibiotics used to treat common bacterial diseases, such as diarrhea, STIs, sepsis, and urinary tract infections, indicate that our supply of effective antibiotics is running low. The mechanisms of action of several antibiotic groups are covered in this review. Antimicrobials disrupt the development and metabolism of bacteria, leading to their eventual death. However, in recent years, microorganisms become resistant to the drugs. Bacteria encode resistant genes against antibiotics and inhibit the function of antibiotics by reducing the uptake of drugs, modifying the enzyme's active site, synthesizing enzymes to degrade antibiotics, and changing the structure of ribosomal subunits. Additionally, the methods of action of resistant bacteria against different kinds of antibiotics as well as their modes of action are discussed. Besides, the resistant pathogenic bacteria which get the most priority by World Health Organisation (WHO) for synthesizing new drugs, have also been incorporated. To overcome antimicrobial resistance, nanomaterials are used to increase the efficacy of antimicrobial drugs. Metallic, inorganic, and polymer-based nanoparticles once conjugated with antibacterial drugs, exhibit synergistic effects by increasing the efficacy of the drugs by inhibiting bacterial growth. Nanomaterial's toxic properties are proportional to their concentrations. Higher concentration nanomaterials are more toxic to the cells. In this review, the toxic properties of nanomaterials on lung cells, lymph nodes, and neuronal cells are also summarized. | 2024 | 38097117 |
| 9524 | 11 | 0.9992 | The Role of Nitroreductases in Resistance to Nitroimidazoles. Antimicrobial resistance is a major challenge facing modern medicine, with an estimated 700,000 people dying annually and a global cost in excess of $100 trillion. This has led to an increased need to develop new, effective treatments. This review focuses on nitroimidazoles, which have seen a resurgence in interest due to their broad spectrum of activity against anaerobic Gram-negative and Gram-positive bacteria. The role of nitroreductases is to activate the antimicrobial by reducing the nitro group. A decrease in the activity of nitroreductases is associated with resistance. This review will discuss the resistance mechanisms of different disease organisms, including Mycobacterium tuberculosis, Helicobacter pylori and Staphylococcus aureus, and how these impact the effectiveness of specific nitroimidazoles. Perspectives in the field of nitroimidazole drug development are also summarised. | 2021 | 34062712 |
| 9540 | 12 | 0.9992 | Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents. The worldwide escalation of bacterial resistance to conventional medical antibiotics is a serious concern for modern medicine. High prevalence of multidrug-resistant bacteria among bacteria-based infections decreases effectiveness of current treatments and causes thousands of deaths. New improvements in present methods and novel strategies are urgently needed to cope with this problem. Owing to their antibacterial activities, metallic nanoparticles represent an effective solution for overcoming bacterial resistance. However, metallic nanoparticles are toxic, which causes restrictions in their use. Recent studies have shown that combining nanoparticles with antibiotics not only reduces the toxicity of both agents towards human cells by decreasing the requirement for high dosages but also enhances their bactericidal properties. Combining antibiotics with nanoparticles also restores their ability to destroy bacteria that have acquired resistance to them. Furthermore, nanoparticles tagged with antibiotics have been shown to increase the concentration of antibiotics at the site of bacterium-antibiotic interaction, and to facilitate binding of antibiotics to bacteria. Likewise, combining nanoparticles with antimicrobial peptides and essential oils generates genuine synergy against bacterial resistance. In this article, we aim to summarize recent studies on interactions between nanoparticles and antibiotics, as well as other antibacterial agents to formulate new prospects for future studies. Based on the promising data that demonstrated the synergistic effects of antimicrobial agents with nanoparticles, we believe that this combination is a potential candidate for more research into treatments for antibiotic-resistant bacteria. | 2011 | 22029522 |
| 8225 | 13 | 0.9992 | Basic peptide-morpholino oligomer conjugate that is very effective in killing bacteria by gene-specific and nonspecific modes. Basic peptides covalently linked to nucleic acids, or chemically modified nucleic acids, enable the insertion of such a conjugate into bacteria grown in liquid medium and mammalian cells in tissue culture. A unique peptide, derived from human T cells, has been employed in a chemical synthesis to make a conjugate with a morpholino oligonucleotide. This new conjugate is at least 10- to 100-fold more effective than previous peptides used in altering the phenotype of host bacteria if the external guide sequence methodology is employed in these experiments. Bacteria with target genes expressing chloramphenicol resistance, penicillin resistance, or gyrase A function can effectively be reduced in their expression and the host cells killed. Several bacteria are susceptible to this treatment, which has a broad range of potency. The loss in viability of bacteria is not due only to complementarity with a target RNA and the action of RNase P, but also to a non-gene-specific tight binding of the complexed nontargeted RNA to the basic polypeptide-morpholino oligonucleotide. | 2011 | 21949365 |
| 9138 | 14 | 0.9992 | Carbon-Based Nanomaterials Alter the Behavior and Gene Expression Patterns of Bacteria. One of the most dangerous characteristics of bacteria is their propensity to form biofilms and their resistance to the drugs used in clinical practice today. The total number of genes that can be categorized as virulence genes ranges from a few hundred to more than a thousand. The bacteria employ a variety of mechanisms to regulate the expression of these genes in a coordinated manner during infection. The search for new agents with anti-virulence capacity is therefore crucial. Nanotechnology provides safe platforms for targeted therapies to combat a broad spectrum of microbial infections. As a new class of innovative materials, carbon-based nanomaterials (CBNs), which include carbon dots, carbon nanotubes, graphene, and fullerenes can have strong antibacterial activity. Exposure to CBNs has been shown to affect bacterial gene expression patterns. This study investigated the effect of CBNs on the repression of specific genes related to bacterial virulence/pathogenicity. | 2025 | 39895035 |
| 4433 | 15 | 0.9992 | 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 |
| 9145 | 16 | 0.9992 | A mechanistic perspective on targeting bacterial drug resistance with nanoparticles. Bacterial infections are an important cause of mortality worldwide owing to the prevalence of drug resistant bacteria. Bacteria develop resistance against antimicrobial drugs by several mechanisms such as enzyme inactivation, reduced cell permeability, modifying target site or enzyme, enhanced efflux because of high expression of efflux pumps, biofilm formation or drug-resistance gene expression. New and alternative ways such as nanoparticle (NP) applications are being established to overcome the growing multidrug-resistance in bacteria. NPs have unique antimicrobial characteristics that make them appropriate for medical application to overcome antibiotic resistance. The proposed antibacterial mechanisms of NPs are cell membrane damage, changing cell wall penetration, reactive oxygen species (ROS) production, effect on DNA and proteins, and impact on biofilm formation. The present review mainly focuses on discussing various mechanisms of bacterial drug resistance and the applications of NPs as alternative antibacterial systems. Combination therapy of NPs and antibiotics as a novel approach in medicine towards antimicrobial resistance is also discussed. | 2021 | 33703979 |
| 9447 | 17 | 0.9992 | Modern vaccine development via reverse vaccinology to combat antimicrobial resistance. With the continuous evolution of bacteria, the global antimicrobial resistance health threat is causing millions of deaths yearly. While depending on antibiotics as a primary treatment has its merits, there are no effective alternatives thus far in the pharmaceutical market against some drug-resistant bacteria. In recent years, vaccinology has become a key topic in scientific research. Combining with the growth of technology, vaccine research is seeing a new light where the process is made faster and more efficient. Although less discussed, bacterial vaccine is a feasible strategy to combat antimicrobial resistance. Some vaccines have shown promising results with good efficacy against numerous multidrug-resistant strains of bacteria. In this review, we aim to discuss the findings from studies utilizing reverse vaccinology for vaccine development against some multidrug-resistant bacteria, as well as provide a summary of multi-year bacterial vaccine studies in clinical trials. The advantages of reverse vaccinology in the generation of new bacterial vaccines are also highlighted. Meanwhile, the limitations and future prospects of bacterial vaccine concludes this review. | 2022 | 35642852 |
| 9469 | 18 | 0.9992 | Reversing bacterial resistance to antibiotics by phage-mediated delivery of dominant sensitive genes. Pathogen resistance to antibiotics is a rapidly growing problem, leading to an urgent need for novel antimicrobial agents. Unfortunately, development of new antibiotics faces numerous obstacles, and a method that resensitizes pathogens to approved antibiotics therefore holds key advantages. We present a proof of principle for a system that restores antibiotic efficiency by reversing pathogen resistance. This system uses temperate phages to introduce, by lysogenization, the genes rpsL and gyrA conferring sensitivity in a dominant fashion to two antibiotics, streptomycin and nalidixic acid, respectively. Unique selective pressure is generated to enrich for bacteria that harbor the phages carrying the sensitizing constructs. This selection pressure is based on a toxic compound, tellurite, and therefore does not forfeit any antibiotic for the sensitization procedure. We further demonstrate a possible way of reducing undesirable recombination events by synthesizing dominant sensitive genes with major barriers to homologous recombination. Such synthesis does not significantly reduce the gene's sensitization ability. Unlike conventional bacteriophage therapy, the system does not rely on the phage's ability to kill pathogens in the infected host, but instead, on its ability to deliver genetic constructs into the bacteria and thus render them sensitive to antibiotics prior to host infection. We believe that transfer of the sensitizing cassette by the constructed phage will significantly enrich for antibiotic-treatable pathogens on hospital surfaces. Broad usage of the proposed system, in contrast to antibiotics and phage therapy, will potentially change the nature of nosocomial infections toward being more susceptible to antibiotics rather than more resistant. | 2012 | 22113912 |
| 9587 | 19 | 0.9992 | 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 |