# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 9124 | 0 | 1.0000 | The role of bacterial membrane vesicles in antibiotic resistance. Bacterial survival during antibiotic exposure is a complex and multifaceted phenomenon. On top of antibiotic resistance genes, biofilm formation, and persister tolerance, bacterial membrane vesicles (MVs) provide a layer of protection that has been largely overlooked. MVs are spherical nanoparticles composed of lipid membranes and are common to Gram-positive and Gram-negative bacteria. Although the importance of MVs in bacterial pathogenesis and virulence factor transport has been firmly established, a growing body of work now identifies MVs as key contributors to bacterial survival during antibiotic exposure. Herein, we highlight the ability of MVs to reduce antibiotic efficacy and transmit resistance elements. We also discuss the potential of targeting MV production as an unconventional therapeutic approach. | 2023 | 36415037 |
| 9427 | 1 | 0.9997 | Polysaccharides' Structures and Functions in Biofilm Architecture of Antimicrobial-Resistant (AMR) Pathogens. Bacteria and fungi have developed resistance to the existing therapies such as antibiotics and antifungal drugs, and multiple mechanisms are mediating this resistance. Among these, the formation of an extracellular matrix embedding different bacterial cells, called biofilm, is an effective strategy through which bacterial and fungal cells are establishing a relationship in a unique environment. The biofilm provides them the possibility to transfer genes conferring resistance, to prevent them from desiccation and to impede the penetration of antibiotics or antifungal drugs. Biofilms are formed of several constituents including extracellular DNA, proteins and polysaccharides. Depending on the bacteria, different polysaccharides form the biofilm matrix in different microorganisms, some of them involved in the first stage of cells' attachment to surfaces and to each other, and some responsible for giving the biofilm structure resistance and stability. In this review, we describe the structure and the role of different polysaccharides in bacterial and fungal biofilms, we revise the analytical methods to characterize them quantitatively and qualitatively and finally we provide an overview of potential new antimicrobial therapies able to inhibit biofilm formation by targeting exopolysaccharides. | 2023 | 36835442 |
| 9472 | 2 | 0.9997 | Bacteriophage and Bacterial Susceptibility, Resistance, and Tolerance to Antibiotics. Bacteriophages, viruses that infect and replicate within bacteria, impact bacterial responses to antibiotics in complex ways. Recent studies using lytic bacteriophages to treat bacterial infections (phage therapy) demonstrate that phages can promote susceptibility to chemical antibiotics and that phage/antibiotic synergy is possible. However, both lytic and lysogenic bacteriophages can contribute to antimicrobial resistance. In particular, some phages mediate the horizontal transfer of antibiotic resistance genes between bacteria via transduction and other mechanisms. In addition, chronic infection filamentous phages can promote antimicrobial tolerance, the ability of bacteria to persist in the face of antibiotics. In particular, filamentous phages serve as structural elements in bacterial biofilms and prevent the penetration of antibiotics. Over time, these contributions to antibiotic tolerance favor the selection of resistance clones. Here, we review recent insights into bacteriophage contributions to antibiotic susceptibility, resistance, and tolerance. We discuss the mechanisms involved in these effects and address their impact on bacterial fitness. | 2022 | 35890320 |
| 9248 | 3 | 0.9997 | Towards an integrated model of bacterial conjugation. Bacterial conjugation is one of the main mechanisms for horizontal gene transfer. It constitutes a key element in the dissemination of antibiotic resistance and virulence genes to human pathogenic bacteria. DNA transfer is mediated by a membrane-associated macromolecular machinery called Type IV secretion system (T4SS). T4SSs are involved not only in bacterial conjugation but also in the transport of virulence factors by pathogenic bacteria. Thus, the search for specific inhibitors of different T4SS components opens a novel approach to restrict plasmid dissemination. This review highlights recent biochemical and structural findings that shed new light on the molecular mechanisms of DNA and protein transport by T4SS. Based on these data, a model for pilus biogenesis and substrate transfer in conjugative systems is proposed. This model provides a renewed view of the mechanism that might help to envisage new strategies to curb the threating expansion of antibiotic resistance. | 2015 | 25154632 |
| 9541 | 4 | 0.9996 | 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 |
| 9430 | 5 | 0.9996 | Mechanisms of antimicrobial resistance in biofilms. Most bacteria in nature exist in aggregated communities known as biofilms, and cells within a biofilm demonstrate major physiological changes compared to their planktonic counterparts. Biofilms are associated with many different types of infections which can have severe impacts on patients. Infections involving a biofilm component are often chronic and highly recalcitrant to antibiotic therapy as a result of intrinsic physical factors including extracellular matrix production, low growth rates, altered antibiotic target production and efficient exchange of resistance genes. This review describes the biofilm lifecycle, phenotypic characteristics of a biofilm, and contribution of matrix and persister cells to biofilms intrinsic tolerance to antimicrobials. We also describe how biofilms can evolve antibiotic resistance and transfer resistance genes within biofilms. Multispecies biofilms and the impacts of various interactions, including cooperation and competition, between species on tolerance to antimicrobials in polymicrobial biofilm communities are also discussed. | 2024 | 39364333 |
| 9215 | 6 | 0.9996 | Bacterial type IV secretion systems and spread of antimicrobial resistance: a study of potential inhibitors to T4SS-based resistance spread. Antimicrobial resistance (AMR) is a major global health threat, mainly driven by the rapid spread of resistance genes through horizontal gene transfer (HGT). The Type IV Secretion System (T4SS) acts as a crucial molecular machinery that facilitates this process, allowing bacteria to transfer DNA, effector proteins, and virulence factors. This review systematically explores the structural and functional diversity of T4SS, its role in spreading AMR, and current methods for its inhibition. T4SS consists of a multi-protein complex that spans bacterial membranes, mediating conjugative plasmid transfer, host-pathogen interactions, and bacterial competition. Key components include ATPases, pilus structures, and membrane-associated proteins that show both conserved features and species-specific adaptations. These traits enable functional specialization across Gram-positive and Gram-negative bacteria, significantly contributing to the spread of vital resistance genes like extended-spectrum β-lactamases and carbapenemases via mobile genetic elements. Several approaches have been developed to inhibit T4SS and combat AMR. Small molecules targeting ATPase activity or protein interactions are promising, as are natural phytochemicals that interfere with conjugation. Bacteriophage therapy provides another strategy by specifically targeting plasmid-carrying bacteria. Host immune responses, such as innate immune recognition and secretory immunoglobulins, also show potential to influence T4SS activity. Although progress has been made, challenges remain, especially in developing selective inhibition methods that do not harm beneficial microbiota or host cells. Future research should focus on high-resolution structural studies to support rational drug design and preclinical testing of combination therapies that include T4SS inhibitors with existing antibiotics. Gaining a deeper understanding of T4SS regulation and host-pathogen interactions will be vital for creating targeted AMR strategies that also maintain ecological balance. | 2025 | 40956426 |
| 9127 | 7 | 0.9996 | 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 |
| 9135 | 8 | 0.9996 | 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 |
| 9154 | 9 | 0.9996 | Interactions of plasma-activated water with biofilms: inactivation, dispersal effects and mechanisms of action. Biofilms have several characteristics that ensure their survival in a range of adverse environmental conditions, including high cell numbers, close cell proximity to allow easy genetic exchange (e.g., for resistance genes), cell communication and protection through the production of an exopolysaccharide matrix. Together, these characteristics make it difficult to kill undesirable biofilms, despite the many studies aimed at improving the removal of biofilms. An elimination method that is safe, easy to deliver in physically complex environments and not prone to microbial resistance is highly desired. Cold atmospheric plasma, a lightning-like state generated from air or other gases with a high voltage can be used to make plasma-activated water (PAW) that contains many active species and radicals that have antimicrobial activity. Recent studies have shown the potential for PAW to be used for biofilm elimination without causing the bacteria to develop significant resistance. However, the precise mode of action is still the subject of debate. This review discusses the formation of PAW generated species and their impacts on biofilms. A focus is placed on the diffusion of reactive species into biofilms, the formation of gradients and the resulting interaction with the biofilm matrix and specific biofilm components. Such an understanding will provide significant benefits for tackling the ubiquitous problem of biofilm contamination in food, water and medical areas. | 2021 | 33504802 |
| 9596 | 10 | 0.9996 | Revealing AMP mechanisms of action through resistance evolution and quantitative proteomics. Antimicrobial resistance (AMR) is a significant public health issue that threatens our ability to treat common infections. AMR often emerges in bacteria through upregulation of proteins that allow a subpopulation of resistant bacteria to proliferate through natural selection. Identifying these proteins is crucial for understanding how AMR develops in bacteria and is essential in developing novel therapeutics to combat the threat of widespread AMR. Mass spectrometry-based proteomics is a powerful tool for understanding the biochemical pathways of biological systems, lending remarkable insight into AMR mechanisms in bacteria through measuring the changing protein abundances as a result of antibiotic treatment. Here, we describe a serial passaging method for evolving resistance in bacteria that implements quantitative proteomics to reveal the differential proteomes of resistant bacteria. The focus herein is on antimicrobial peptides (AMPs), but the approach can be generalized for any antimicrobial compound. Comparative proteomics of sensitive vs. resistance strains in response to AMP treatment reveals mechanisms to survive the bioactive compound and points to the mechanism of action for novel AMPs. | 2022 | 35168792 |
| 9128 | 11 | 0.9996 | Molecular Mechanisms of Bacterial Resistance to Antimicrobial Peptides in the Modern Era: An Updated Review. Antimicrobial resistance (AMR) poses a serious global health concern, resulting in a significant number of deaths annually due to infections that are resistant to treatment. Amidst this crisis, antimicrobial peptides (AMPs) have emerged as promising alternatives to conventional antibiotics (ATBs). These cationic peptides, naturally produced by all kingdoms of life, play a crucial role in the innate immune system of multicellular organisms and in bacterial interspecies competition by exhibiting broad-spectrum activity against bacteria, fungi, viruses, and parasites. AMPs target bacterial pathogens through multiple mechanisms, most importantly by disrupting their membranes, leading to cell lysis. However, bacterial resistance to host AMPs has emerged due to a slow co-evolutionary process between microorganisms and their hosts. Alarmingly, the development of resistance to last-resort AMPs in the treatment of MDR infections, such as colistin, is attributed to the misuse of this peptide and the high rate of horizontal genetic transfer of the corresponding resistance genes. AMP-resistant bacteria employ diverse mechanisms, including but not limited to proteolytic degradation, extracellular trapping and inactivation, active efflux, as well as complex modifications in bacterial cell wall and membrane structures. This review comprehensively examines all constitutive and inducible molecular resistance mechanisms to AMPs supported by experimental evidence described to date in bacterial pathogens. We also explore the specificity of these mechanisms toward structurally diverse AMPs to broaden and enhance their potential in developing and applying them as therapeutics for MDR bacteria. Additionally, we provide insights into the significance of AMP resistance within the context of host-pathogen interactions. | 2024 | 39065030 |
| 9549 | 12 | 0.9996 | Mechanism of escape from the antibacterial activity of metal-based nanoparticles in clinically relevant bacteria: A systematic review. The emergency of antibiotic-resistant bacteria in severe infections is increasing, especially in nosocomial environments. The ESKAPE group is of special importance in the groups of multi-resistant bacteria due to its high capacity to generate resistance to antibiotics and bactericides. Therefore, metal-based nanomaterials are an attractive alternative to combat them because they have been demonstrated to damage biomolecules in the bacterial cells. However, there is a concern about bacteria developing resistance to NPs and their harmful effects due to environmental accumulation. Therefore, this systematic review aims to report the clinically relevant bacteria that have developed resistance to the NPs. According to the results of this systematic review, various mechanisms to counteract the antimicrobial activity of various NP types have been proposed. These mechanisms can be grouped into the following categories: production of extracellular compounds, metal efflux pumps, ROS response, genetic changes, DNA repair, adaptative morphogenesis, and changes in the plasma membrane. | 2024 | 37907198 |
| 9129 | 13 | 0.9996 | Overcoming Intrinsic and Acquired Resistance Mechanisms Associated with the Cell Wall of Gram-Negative Bacteria. The global increase in multi-drug-resistant bacteria is severely impacting our ability to effectively treat common infections. For Gram-negative bacteria, their intrinsic and acquired resistance mechanisms are heightened by their unique cell wall structure. The cell wall, while being a target of some antibiotics, represents a barrier due to the inability of most antibacterial compounds to traverse and reach their intended target. This means that its composition and resulting mechanisms of resistance must be considered when developing new therapies. Here, we discuss potential antibiotic targets within the most well-characterised resistance mechanisms associated with the cell wall in Gram-negative bacteria, including the outer membrane structure, porins and efflux pumps. We also provide a timely update on the current progress of inhibitor development in these areas. Such compounds could represent new avenues for drug discovery as well as adjuvant therapy to help us overcome antibiotic resistance. | 2020 | 32961699 |
| 9263 | 14 | 0.9996 | The F-pilus biomechanical adaptability accelerates conjugative dissemination of antimicrobial resistance and biofilm formation. Conjugation is used by bacteria to propagate antimicrobial resistance (AMR) in the environment. Central to this process are widespread conjugative F-pili that establish the connection between donor and recipient cells, thereby facilitating the spread of IncF plasmids among enteropathogenic bacteria. Here, we show that the F-pilus is highly flexible but robust at the same time, properties that increase its resistance to thermochemical and mechanical stresses. By a combination of biophysical and molecular dynamics methods, we establish that the presence of phosphatidylglycerol molecules in the F-pilus contributes to the structural stability of the polymer. Moreover, this structural stability is important for successful delivery of DNA during conjugation and facilitates rapid formation of biofilms in harsh environmental conditions. Thus, our work highlights the importance of F-pilus structural adaptations for the efficient spread of AMR genes in a bacterial population and for the formation of biofilms that protect against the action of antibiotics. | 2023 | 37019921 |
| 9614 | 15 | 0.9996 | Antibiotic-Independent Adaptive Effects of Antibiotic Resistance Mutations. Antibiotic usage selects for the accumulation and spread of antibiotic-resistant bacteria. However, resistance can also accumulate in the absence of antibiotic exposure. Antibiotics are often designed to target widely distributed regulatory housekeeping genes. The targeting of such genes enables these antibiotics to be useful against a wider variety of pathogens. This review highlights work suggesting that regulatory housekeeping genes of the type targeted by many antibiotics function as hubs of adaptation to conditions unrelated to antibiotic exposure. As a result of this, some mutations to the regulatory housekeeping gene targets of antibiotics confer both antibiotic resistance and an adaptive effect unrelated to antibiotic exposure. Such antibiotic-independent adaptive effects of resistance mutations may substantially affect the dynamics of antibiotic resistance accumulation and spread. | 2017 | 28629950 |
| 9622 | 16 | 0.9996 | Stable Neutralization of a Virulence Factor in Bacteria Using Temperate Phage in the Mammalian Gut. Elimination or alteration of select members of the gut microbiota is key to therapeutic efficacy. However, the complexity of these microbial inhabitants makes it challenging to precisely target bacteria. Here, we deliver exogenous genes to specific bacteria by genomic integration of temperate phage for long-lasting modification. As a real-world therapeutic test, we engineered λ phage to transcriptionally repress Shiga toxin by using genetic hybrids between λ and other lambdoid phages to overcome resistance encoded by the virulence-expressing prophage. We show that a single dose of engineered phage propagates throughout the bacterial community and reduces Shiga toxin production in an enteric mouse model of infection without markedly affecting bacterial concentrations. Our work reveals a new framework for transferring functions to bacteria within their native environment.IMPORTANCE With the increasing frequency of antibiotic resistance, it is critical to explore new therapeutic strategies for treating bacterial infections. Here, we use a temperate phage, i.e., one that integrates itself into the bacterial genome, to neutralize the expression of a virulence factor by modifying bacterial function at the genetic level. We show that Shiga toxin production can be significantly reduced in vitro and in the mammalian gut. Alternative to traditional applications of phage therapy that rely on killing bacteria, our genetics-based antivirulence approach introduces a new framework for treating bacterial infections. | 2020 | 31992629 |
| 9133 | 17 | 0.9996 | 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 |
| 9140 | 18 | 0.9996 | Polyamine as a microenvironment factor in resistance to antibiotics. One of the main issues in modern medicine is the decrease in the efficacy of antibiotic therapy against resistant microorganisms. The advent of antimicrobial resistance has added significantly to the impact of infectious diseases, in number of infections, as well as added healthcare costs. The development of antibiotic tolerance and resistance is influenced by a variety of environmental variables, and it is important to identify these environmental factors as part of any strategy for combating antibiotic resistance. The review aims to emphasize that biogenic polyamines are one of such environmental cues that impacts the antibiotic resistance in bacteria. The biogenic polyamines can help bacteria acquire resistance to antibiotics either by regulating the level of number of porin channels in the outer membrane, by modifying the outer membrane liposaccharides or by protecting macromolecule from antibiotic stress. Thus, understanding the way polyamines function in bacteria can thus be beneficial while designing the drugs to combat diseases. | 2024 | 37339480 |
| 9548 | 19 | 0.9996 | Molecular Mechanisms of Bacterial Resistance to Metal and Metal Oxide Nanoparticles. The increase in bacterial resistance to one or several antibiotics has become a global health problem. Recently, nanomaterials have become a tool against multidrug-resistant bacteria. The metal and metal oxide nanoparticles are one of the most studied nanomaterials against multidrug-resistant bacteria. Several in vitro studies report that metal nanoparticles have antimicrobial properties against a broad spectrum of bacterial species. However, until recently, the bacterial resistance mechanisms to the bactericidal action of the nanoparticles had not been investigated. Some of the recently reported resistance mechanisms include electrostatic repulsion, ion efflux pumps, expression of extracellular matrices, and the adaptation of biofilms and mutations. The objective of this review is to summarize the recent findings regarding the mechanisms used by bacteria to counteract the antimicrobial effects of nanoparticles. | 2019 | 31181755 |