# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 9088 | 0 | 0.9943 | 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 |
| 8160 | 1 | 0.9942 | Quorum Sensing in Gram-Negative Bacteria: Strategies to Overcome Antibiotic Resistance in Ocular Infections. Truly miraculous medications and antibiotics have helped save untold millions of lives. Antibiotic resistance, however, is a significant issue related to health that jeopardizes the effectiveness of antibiotics and could harm everyone's health. Bacteria, not humans or animals, become antibiotic-resistant. Bacteria use quorum-sensing communication routes to manage an assortment of physiological exercises. Quorum sensing is significant for appropriate biofilm development. Antibiotic resistance occurs when bacteria establish a biofilm on a surface, shielding them from the effects of infection-fighting drugs. Acylated homoserine lactones are used as autoinducers by gram-negative microscopic organisms to impart. However, antibiotic resistance among ocular pathogens is increasing worldwide. Bacteria are a significant contributor to ocular infections around the world. Gram-negative microscopic organisms are dangerous to ophthalmic tissues. This review highlights the use of elective drug targets and treatments, for example, combinational treatment, to vanquish antibiotic-resistant bacteria. Also, it briefly portrays anti-biotic resistance brought about by gram-negative bacteria and approaches to overcome resistance with the help of quorum sensing inhibitors and nanotechnology as a promising medication conveyance approach to give insurance of anti-microbials and improve pathways for the administration of inhibitors of quorum sensing with a blend of anti-microbials to explicit target destinations and penetration through biofilms for treatment of ocular infections. It centres on the methodologies to sidestep the confinements of ocular anti-biotic delivery with new visual innovation. | 2024 | 37497706 |
| 9087 | 2 | 0.9941 | Complementary supramolecular drug associates in perfecting the multidrug therapy against multidrug resistant bacteria. The inappropriate and inconsistent use of antibiotics in combating multidrug-resistant bacteria exacerbates their drug resistance through a few distinct pathways. Firstly, these bacteria can accumulate multiple genes, each conferring resistance to a specific drug, within a single cell. This accumulation usually takes place on resistance plasmids (R). Secondly, multidrug resistance can arise from the heightened expression of genes encoding multidrug efflux pumps, which expel a broad spectrum of drugs from the bacterial cells. Additionally, bacteria can also eliminate or destroy antibiotic molecules by modifying enzymes or cell walls and removing porins. A significant limitation of traditional multidrug therapy lies in its inability to guarantee the simultaneous delivery of various drug molecules to a specific bacterial cell, thereby fostering incremental drug resistance in either of these paths. Consequently, this approach prolongs the treatment duration. Rather than using a biologically unimportant coformer in forming cocrystals, another drug molecule can be selected either for protecting another drug molecule or, can be selected for its complementary activities to kill a bacteria cell synergistically. The development of a multidrug cocrystal not only improves tabletability and plasticity but also enables the simultaneous delivery of multiple drugs to a specific bacterial cell, philosophically perfecting multidrug therapy. By adhering to the fundamental tenets of multidrug therapy, the synergistic effects of these drug molecules can effectively eradicate bacteria, even before they have the chance to develop resistance. This approach has the potential to shorten treatment periods, reduce costs, and mitigate drug resistance. Herein, four hypotheses are presented to create complementary drug cocrystals capable of simultaneously reaching bacterial cells, effectively destroying them before multidrug resistance can develop. The ongoing surge in the development of novel drugs provides another opportunity in the fight against bacteria that are constantly gaining resistance to existing treatments. This endeavour holds the potential to combat a wide array of multidrug-resistant bacteria. | 2024 | 38415251 |
| 9175 | 3 | 0.9941 | Fitness Trade-Offs Resulting from Bacteriophage Resistance Potentiate Synergistic Antibacterial Strategies. Bacteria that cause life-threatening infections in humans are becoming increasingly difficult to treat. In some instances, this is due to intrinsic and acquired antibiotic resistance, indicating that new therapeutic approaches are needed to combat bacterial pathogens. There is renewed interest in utilizing viruses of bacteria known as bacteriophages (phages) as potential antibacterial therapeutics. However, critics suggest that similar to antibiotics, the development of phage-resistant bacteria will halt clinical phage therapy. Although the emergence of phage-resistant bacteria is likely inevitable, there is a growing body of literature showing that phage selective pressure promotes mutations in bacteria that allow them to subvert phage infection, but with a cost to their fitness. Such fitness trade-offs include reduced virulence, resensitization to antibiotics, and colonization defects. Resistance to phage nucleic acid entry, primarily via cell surface modifications, compromises bacterial fitness during antibiotic and host immune system pressure. In this minireview, we explore the mechanisms behind phage resistance in bacterial pathogens and the physiological consequences of acquiring phage resistance phenotypes. With this knowledge, it may be possible to use phages to alter bacterial populations, making them more tractable to current therapeutic strategies. | 2020 | 32094257 |
| 8161 | 4 | 0.9941 | 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 |
| 9476 | 5 | 0.9940 | 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 |
| 9446 | 6 | 0.9939 | 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 |
| 9174 | 7 | 0.9939 | 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 |
| 9118 | 8 | 0.9939 | Essential Oils and Their Components as Modulators of Antibiotic Activity against Gram-Negative Bacteria. Gram-negative bacteria cause infections that are difficult to treat due to the emergence of multidrug resistance. This review summarizes the current status of the studies investigating the capacity of essential oils and their components to modulate antibiotic activity against Gram-negative bacteria. Synergistic interactions are particularly discussed with reference to possible mechanisms by which essential oil constituents interact with antibiotics. Special emphasis is given to essential oils and volatile compounds that inhibit efflux pumps, thus reversing drug resistance in Gram-negative bacteria. In addition, indifference and antagonism between essential oils/volatile compounds and conventional antibiotics have also been reported. Overall, this literature review reveals that essential oils and their purified components enhance the efficacy of antibiotics against Gram-negative bacteria, being promising candidates for the development of new effective formulations against Gram-negative bacteria. | 2016 | 28930130 |
| 9099 | 9 | 0.9938 | Small molecule downregulation of PmrAB reverses lipid A modification and breaks colistin resistance. Infections caused by multi-drug resistant bacteria, particularly Gram-negative bacteria, are an ever-increasing problem. While the development of new antibiotics remains one option in the fight against bacteria that have become resistant to currently available antibiotics, an attractive alternative is the development of adjuvant therapeutics that restore the efficacy of existing antibiotics. We report a small molecule adjuvant that suppresses colistin resistance in multidrug resistant Acinetobacter baumannii and Klebsiella pneumoniae by interfering with the expression of a two-component system. The compound downregulates the pmrCAB operon and reverses phosphoethanolamine modification of lipid A responsible for colistin resistance. Furthermore, colistin-susceptible and colistin-resistant bacteria do not evolve resistance to combination treatment. This represents the first definitive example of a compound that breaks antibiotic resistance by directly modulating two-component system activity. | 2014 | 24131198 |
| 9177 | 10 | 0.9938 | 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 |
| 8158 | 11 | 0.9938 | Nanobioconjugates: Weapons against Antibacterial Resistance. The increase in drug resistance in pathogenic bacteria is emerging as a global threat as we swiftly edge toward the postantibiotic era. Nanobioconjugates have gained tremendous attention to treat multidrug-resistant (MDR) bacteria and biofilms due to their tunable physicochemical properties, drug targeting ability, enhanced uptake, and alternate mechanisms of drug action. In this review, we highlight the recent advances made in the use of nanobioconjugates to combat antibacterial resistance and provide crucial insights for designing nanomaterials that can serve as antibacterial agents for nanotherapeutics, nanocargos for targeted antibiotic delivery, or both. Also discussed are different strategies for treating robust biofilms formed by bacteria. | 2020 | 35019602 |
| 9445 | 12 | 0.9938 | Bacteriophages of Mycobacterium tuberculosis, their diversity, and potential therapeutic uses: a review. Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tuberculosis) is a highly infectious disease and worldwide health problem. Based on the WHO TB report, 9 million active TB cases are emerging, leading to 2 million deaths each year. The recent emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains emphasizes the necessity to improve novel therapeutic plans. Among the various developing antibacterial approaches, phage therapy is thought to be a precise hopeful resolution. Mycobacteriophages are viruses that infect bacteria such as Mycobacterium spp., containing the M. tuberculosis complex. Phages and phage-derived proteins can act as promising antimicrobial agents. Also, phage cocktails can broaden the spectrum of lysis activity against bacteria. Recent researches have also shown the effective combination of antibiotics and phages to defeat the infective bacteria. There are limitations and concerns about phage therapy. For example, human immune response to phage therapy, transferring antibiotic resistance genes, emerging resistance to phages, and safety issues. So, in the present study, we introduced mycobacteriophages, their use as therapeutic agents, and their advantages and limitations as therapeutic applications. | 2022 | 36550444 |
| 9059 | 13 | 0.9938 | Validation of Suitable Carrier Molecules and Target Genes for Antisense Therapy Using Peptide-Coupled Peptide Nucleic Acids (PNAs) in Streptococci. Antisense peptide nucleic acids (PNAs) targeting genes involved in metabolism or virulence are a possible means to treat infections or to investigate pathogenic bacteria. Potential targets include essential genes, virulence factor genes, or antibiotic resistance genes. For efficient cellular uptake, PNAs can be coupled to cell-penetrating peptides (CPPs). CPPs are peptides that serve as molecular transporters and are characterized by a comparably low cytotoxicity. So far, there is only limited information about CPPs that mediate PNA uptake by Gram-positive bacteria. Here, we describe two methods to identify suitable CPP-antisense PNA conjugates, novel carrier molecules, and efficient target genes for streptococcal species and to evaluate their antimicrobial efficiency. | 2020 | 32430835 |
| 9183 | 14 | 0.9938 | Overcoming Bacteriophage Resistance in Phage Therapy. Antibiotic resistance among pathogenic bacteria is one of the most severe global challenges. It is predicted that over ten million lives will be lost annually by 2050. Phage therapy is a promising alternative to antibiotics. However, the ease of development of phage resistance during therapy is a concern. This review focuses on the possible ways to overcome phage resistance in phage therapy. | 2024 | 37966611 |
| 9141 | 15 | 0.9937 | 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 |
| 9814 | 16 | 0.9937 | 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 |
| 9539 | 17 | 0.9937 | Materials for restoring lost Activity: Old drugs for new bugs. The escalation of bacterial resistance to conventional medical antibiotics is a serious concern worldwide. Improvements to current therapies are urgently needed to address this problem. The synergistic combination of antibiotics with other agents is a strategic solution to combat multi-drug-resistant bacteria. Although these combinations decrease the required high dosages and therefore, reduce the toxicity of both agents without compromising the bactericidal effect, they cannot stop the development of further resistance. Recent studies have shown certain elements restore the ability of antibiotics to destroy bacteria that have acquired resistance to them. Due to these synergistic activities, organic and inorganic molecules have been investigated with the goal of restoring antibiotics in new approaches that mitigate the risk of expanding resistance. Herein, we summarize recent studies that restore antibiotics once thought to be ineffective, but have returned to our armamentarium through innovative, combinatorial efforts. A special focus is placed on the mechanisms that allow the synergistic combinations to combat bacteria. The promising data that demonstrated restoration of antimicrobials, supports the notion to find more combinations that can combat antibiotic-resistant bacteria. | 2022 | 35461913 |
| 9221 | 18 | 0.9937 | Breaking antimicrobial resistance by disrupting extracytoplasmic protein folding. Antimicrobial resistance in Gram-negative bacteria is one of the greatest threats to global health. New antibacterial strategies are urgently needed, and the development of antibiotic adjuvants that either neutralize resistance proteins or compromise the integrity of the cell envelope is of ever-growing interest. Most available adjuvants are only effective against specific resistance proteins. Here, we demonstrate that disruption of cell envelope protein homeostasis simultaneously compromises several classes of resistance determinants. In particular, we find that impairing DsbA-mediated disulfide bond formation incapacitates diverse β-lactamases and destabilizes mobile colistin resistance enzymes. Furthermore, we show that chemical inhibition of DsbA sensitizes multidrug-resistant clinical isolates to existing antibiotics and that the absence of DsbA, in combination with antibiotic treatment, substantially increases the survival of Galleria mellonella larvae infected with multidrug-resistant Pseudomonas aeruginosa. This work lays the foundation for the development of novel antibiotic adjuvants that function as broad-acting resistance breakers. | 2022 | 35025730 |
| 9158 | 19 | 0.9937 | Quorum sensing pathways in Gram-positive and -negative bacteria: potential of their interruption in abating drug resistance. Quorum sensing (QS) is an inter-cell communication between bacterial populations through release of tiny diffusible compounds as signalling agents, called auto-inducers, abetting bacteria to track population density. QS allows bacterial population to perform collectively in coordination to wide phenotypes like alterations in expression of virulence genes to achieve advancement over their competitors, drug resistance and biofilm formation. Several classes of autoinducers have been described that are involved in bacterial virulence. This review gives an insight into the multitudinous QS systems in Gram-positive and Gram-negative bacteria to explore their role in microbial physiology and pathogenesis. Bacterial resistance to antibiotics has clinically become a super challenge. Strategies to interrupt QS pathways by natural and synthetic QS inhibitors or quorum quenchers or analogs provide a potential treatment. We highlight the advancements in discovery of promising new targets for development of next generation antimicrobials to control infections caused by multidrug resistant bacterial pathogens. | 2019 | 31007147 |