# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 4286 | 0 | 1.0000 | Disinfectant resistance in bacteria: Mechanisms, spread, and resolution strategies. Disinfectants are widely acknowledged for removing microorganisms from the surface of the objects and transmission media. However, the emergence of disinfectant resistance has become a severe threat to the safety of life and health and the rational allocation of resources due to the reduced disinfectant effectiveness. The horizontal gene transfer (HGT) of disinfectant resistance genes has also expanded the resistant flora, making the situation worse. This review focused on the resistance mechanisms of disinfectant resistant bacteria on biofilms, cell membrane permeability, efflux pumps, degradable enzymes, and disinfectant targets. Efflux can be the fastest and most effective resistance mechanism for bacteria to respond to stress. The qac genes, located on some plasmids which can transmit resistance through conjugative transfer, are the most commonly reported in the study of disinfectant resistance genes. Whether the qac genes can be transferred through transformation or transduction is still unclear. Studying the factors affecting the resistance of bacteria to disinfectants can find breakthrough methods to more adequately deal with the problem of reduced disinfectant effectiveness. It has been confirmed that the interaction of probiotics and bacteria or the addition of 4-oxazolidinone can inhibit the formation of biofilms. Chemicals such as eugenol and indole derivatives can increase bacterial sensitivity by reducing the expression of efflux pumps. The role of these findings in anti-disinfectant resistance has proved invaluable. | 2021 | 33617866 |
| 9435 | 1 | 0.9998 | Why are bacteria refractory to antimicrobials? The incidence of antibiotic resistance in pathogenic bacteria is rising. Antibiotic resistance can be achieved via three distinct routes: inactivation of the drug, modification of the target of action, and reduction in the concentration of drug that reaches the target. It has long been recognized that specific antibiotic resistance mechanisms can be acquired through mutation of the bacterial genome or by gaining additional genes through horizontal gene transfer. Recent attention has also brought to light the importance of different physiological states for the survival of bacteria in the presence of antibiotics. It is now apparent that bacteria have complex, intrinsic resistance mechanisms that are often not detected in the standard antibiotic sensitivity tests performed in clinical laboratories. The development of resistance in bacteria found in surface-associated aggregates or biofilms, owing to these intrinsic mechanisms, is paramount. | 2002 | 12354553 |
| 9684 | 2 | 0.9998 | Pesticide degrading natural multidrug resistance bacterial flora. Multidrug-resistant (MDR) bacteria are a growing threat to humans across the world. Antibiotic resistance is a global problem that has developed through continuous antibiotic use, combinatorial antibiotic use, pesticide-antibiotic cross-resistance, and horizontal gene transfer, as well as various other modes. Pesticide-antibiotic cross-resistance and the subsequent expansion of drug-resistant bacteria are critically documented in this review, the primary focus of which is to assess the impact of indiscriminate pesticide use on the development of microbial communities with parallel pesticide and multidrug resistance. The consumption of pesticide-contaminated food products and the use of broad-spectrum antibiotics by humans and in livestock animals have favored the development of both antibiotic and pesticide-resistant bacterial flora via natural selection. Pesticide resistance mainly develops through defensive bacterial adaptations such as biofilm formation, induced mutations, and horizontal/vertical gene transfer through plasmids or transposons, as well as through the increased expression of certain hydrolytic enzymes. Pesticide resistance genes are always transferred as gene clusters, and they may also carry genes essential for antibiotic resistance. Moreover, for some induced mutations, the mutated active site of the affected enzyme may allow degradation of both pesticides and antibiotics, resulting in cross-resistance. A few studies have shown that the sub-lethal exposure of wild-type strains to herbicides induces antibiotic resistance. This review concludes that xenobiotic exposure leads to cross-resistance in wild microbial flora, which requires further study to develop therapeutic approaches to overcome the threats of MDR bacteria and superbugs. | 2018 | 29223450 |
| 4282 | 3 | 0.9998 | Efflux Pump Inhibitors in Controlling Antibiotic Resistance: Outlook under a Heavy Metal Contamination Context. Multi-drug resistance to antibiotics represents a growing challenge in treating infectious diseases. Outside the hospital, bacteria with the multi-drug resistance (MDR) phenotype have an increased prevalence in anthropized environments, thus implying that chemical stresses, such as metals, hydrocarbons, organic compounds, etc., are the source of such resistance. There is a developing hypothesis regarding the role of metal contamination in terrestrial and aquatic environments as a selective agent in the proliferation of antibiotic resistance caused by the co-selection of antibiotic and metal resistance genes carried by transmissible plasmids and/or associated with transposons. Efflux pumps are also known to be involved in either antibiotic or metal resistance. In order to deal with these situations, microorganisms use an effective strategy that includes a range of expressions based on biochemical and genetic mechanisms. The data from numerous studies suggest that heavy metal contamination could affect the dissemination of antibiotic-resistant genes. Environmental pollution caused by anthropogenic activities could lead to mutagenesis based on the synergy between antibiotic efficacy and the acquired resistance mechanism under stressors. Moreover, the acquired resistance includes plasmid-encoded specific efflux pumps. Soil microbiomes have been reported as reservoirs of resistance genes that are available for exchange with pathogenic bacteria. Importantly, metal-contaminated soil is a selective agent that proliferates antibiotic resistance through efflux pumps. Thus, the use of multi-drug efflux pump inhibitors (EPIs) originating from natural plants or synthetic compounds is a promising approach for restoring the efficacy of existing antibiotics, even though they face a lot of challenges. | 2023 | 37049674 |
| 9549 | 4 | 0.9998 | 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 |
| 9548 | 5 | 0.9998 | 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 |
| 9432 | 6 | 0.9998 | Disinfectants and antiseptics: mechanisms of action and resistance. Chemical biocides are used for the prevention and control of infection in health care, targeted home hygiene or controlling microbial contamination for various industrial processes including but not limited to food, water and petroleum. However, their use has substantially increased since the implementation of programmes to control outbreaks of methicillin-resistant Staphylococcus aureus, Clostridioides difficile and severe acute respiratory syndrome coronavirus 2. Biocides interact with multiple targets on the bacterial cells. The number of targets affected and the severity of damage will result in an irreversible bactericidal effect or a reversible bacteriostatic one. Most biocides primarily target the cytoplasmic membrane and enzymes, although the specific bactericidal mechanisms vary among different biocide chemistries. Inappropriate usage or low concentrations of a biocide may act as a stressor while not killing bacterial pathogens, potentially leading to antimicrobial resistance. Biocides can also promote the transfer of antimicrobial resistance genes. In this Review, we explore our current understanding of the mechanisms of action of biocides, the bacterial resistance mechanisms encompassing both intrinsic and acquired resistance and the influence of bacterial biofilms on resistance. We also consider the impact of bacteria that survive biocide exposure in environmental and clinical contexts. | 2024 | 37648789 |
| 9685 | 7 | 0.9998 | Biofilm: A Hotspot for Emerging Bacterial Genotypes. Bacteria have the ability to adapt to changing environments through rapid evolution mediated by modification of existing genetic information, as well as by horizontal gene transfer (HGT). This makes bacteria a highly successful life form when it comes to survival. Unfortunately, this genetic plasticity may result in emergence and dissemination of antimicrobial resistance and virulence genes, and even the creation of multiresistant "superbugs" which may pose serious threats to public health. As bacteria commonly reside in biofilms, there has been an increased interest in studying these phenomena within biofilms in recent years. This review summarizes the present knowledge within this important area of research. Studies on bacterial evolution in biofilms have shown that mature biofilms develop into diverse communities over time. There is growing evidence that the biofilm lifestyle may be more mutagenic than planktonic growth. Furthermore, all three main mechanisms for HGT have been observed in biofilms. This has been shown to occur both within and between bacterial species, and higher transfer rates in biofilms than in planktonic cultures were detected. Of special concern are the observations that mutants with increased antibiotic resistance occur at higher frequency in biofilms than in planktonic cultures even in the absence of antibiotic exposure. Likewise, efficient dissemination of antimicrobial resistance genes, as well as virulence genes, has been observed within the biofilm environment. This new knowledge emphasizes the importance of biofilm awareness and control. | 2018 | 29914658 |
| 9397 | 8 | 0.9998 | Conjugation Inhibitors Effectively Prevent Plasmid Transmission in Natural Environments. Plasmid conjugation is a major route for the spread of antibiotic resistance genes. Inhibiting conjugation has been proposed as a feasible strategy to stop or delay the propagation of antibiotic resistance genes. Several compounds have been shown to be conjugation inhibitors in vitro, specifically targeting the plasmid horizontal transfer machinery. However, the in vivo efficiency and the applicability of these compounds to clinical and environmental settings remained untested. Here we show that the synthetic fatty acid 2-hexadecynoic acid (2-HDA), when used as a fish food supplement, lowers the conjugation frequency of model plasmids up to 10-fold in controlled water microcosms. When added to the food for mice, 2-HDA diminished the conjugation efficiency 50-fold in controlled plasmid transfer assays carried out in the mouse gut. These results demonstrate the in vivo efficiency of conjugation inhibitors, paving the way for their potential application in clinical and environmental settings. IMPORTANCE The spread of antibiotic resistance is considered one of the major threats for global health in the immediate future. A key reason for the speed at which antibiotic resistance spread is the ability of bacteria to share genes with each other. Antibiotic resistance genes harbored in plasmids can be easily transferred to commensal and pathogenic bacteria through a process known as bacterial conjugation. Blocking conjugation is thus a potentially useful strategy to curtail the propagation of antibiotic resistance. Conjugation inhibitors (COINS) are a series of compounds that block conjugation in vitro. Here we show that COINS efficiently block plasmid transmission in two controlled natural environments, water microcosms and the mouse gut. These observations indicate that COIN therapy can be used to prevent the spread of antibiotic resistance. | 2021 | 34425705 |
| 9686 | 9 | 0.9998 | Selective pressures for public antibiotic resistance. The rapid increase of antibiotic-resistant pathogens is severely limiting our current treatment possibilities. An important subset of the resistance mechanisms conferring antibiotic resistance have public effects, allowing otherwise susceptible bacteria to also survive antibiotic treatment. As susceptible bacteria can survive treatment without bearing the metabolic cost of producing the resistance mechanism, there is potential to increase their relative frequency in the population and, as such, select against resistant bacteria. Multiple studies showed that this altered selection for resistance is dependent on various environmental and treatment parameters. In this review, we provide a comprehensive overview of their most important findings and describe the main factors impacting the selection for resistance. In-depth understanding of the driving forces behind selection can aid in the design and implementation of alternative treatments which limit the risk of resistance development. | 2025 | 39158370 |
| 9429 | 10 | 0.9998 | Basic features of biofilms--why are they difficult therapeutic targets? The purpose of this paper is to review the basic features of biofilms associated with human infections and summarize why such biofilms are resistant to antimicrobial agents. The formation of most biofilms involves adherence of bacteria to a conditioned surface, growth and division of the attached bacteria, synthesis of a polymeric slime matrix, formation of a structured microbial community, and incorporation of other micro-organisms into the microbial mass. The transition of bacteria from free-floating (planktonic) to biofilm environments involves extensive up-regulation of genes associated with adherence. Micro-organisms in established biofilms engage in complex integrated activities involving activation and deactivation of genes that promote the survival of bacteria within the biofilm community. Mechanisms of the increased resistance of biofilm bacteria to antimicrobial agents may involve: (1) neutralization or consumption of the drug, (2) failure of the drug to completely penetrate the biofilm, (3) inability of the drug to affect metabolically inactive bacteria, and (4) presence of drug-resistant bacteria within biofilms. | 2004 | 16479852 |
| 9697 | 11 | 0.9998 | Origins and evolution of antibiotic resistance. The massive prescription of antibiotics and their non-regulated and extensive usage has resulted in the development of extensive antibiotic resistance in microorganisms; this has been of great clinical significance. Antibiotic resistance occurs not only by mutation of microbial genes which code for antibiotic uptake into cells or the binding sites for antibiotics, but mostly by the acquisition of heterologous resistance genes from external sources. The physical characteristics of the microbial community play a major role in gene exchange, but antimicrobial agents provide the selective pressure for the development of resistance and promote the transfer of resistance genes among bacteria. The control of antibiotic usage is essential to prevent the development of resistance to new antibiotics. | 1996 | 9019139 |
| 9517 | 12 | 0.9998 | Better together-Salmonella biofilm-associated antibiotic resistance. Salmonella poses a serious threat to public health and socioeconomic development worldwide because of its foodborne pathogenicity and antimicrobial resistance. This biofilm-planktonic lifestyle enables Salmonella to interfere with the host and become resistant to drugs, conferring inherent tolerance to antibiotics. The complex biofilm structure makes bacteria tolerant to harsh conditions due to the diversity of physiological, biochemical, environmental, and molecular factors constituting resistance mechanisms. Here, we provide an overview of the mechanisms of Salmonella biofilm formation and antibiotic resistance, with an emphasis on less-studied molecular factors and in-depth analysis of the latest knowledge about upregulated drug-resistance-associated genes in bacterial aggregates. We classified and extensively discussed each group of these genes encoding transporters, outer membrane proteins, enzymes, multiple resistance, metabolism, and stress response-associated proteins. Finally, we highlighted the missing information and studies that need to be undertaken to understand biofilm features and contribute to eliminating antibiotic-resistant and health-threatening biofilms. | 2023 | 37401756 |
| 9259 | 13 | 0.9998 | Static recipient cells as reservoirs of antibiotic resistance during antibiotic therapy. How does taking the full course of antibiotics prevent antibiotic resistant bacteria establishing in patients? We address this question by testing the possibility that horizontal/lateral gene transfer (HGT) is critical for the accumulation of the antibiotic-resistance phenotype while bacteria are under antibiotic stress. Most antibiotics prevent bacterial reproduction, some by preventing de novo gene expression. Nevertheless, in some cases and at some concentrations, the effects of most antibiotics on gene expression may not be irreversible. If the stress is removed before the bacteria are cleared from the patients by normal turnover, gene expression restarts, converting the residual population to phenotypic resistance. Using mathematical models we investigate how static recipients of resistance genes carried by plasmids accumulate resistance genes, and how specifically an environment cycling between presence and absence of the antibiotic uniquely favors the evolution of horizontally mobile resistance genes. We found that the presence of static recipients can substantially increase the persistence of the plasmid and that this effect is most pronounced when the cost of carriage of the plasmid decreases the cell's growth rate by as much as a half or more. In addition, plasmid persistence can be enhanced even when conjugation rates are as low as half the rate required for the plasmid to persist as a parasite on its own. | 2006 | 16723146 |
| 4075 | 14 | 0.9998 | Antimicrobial resistance in foodborne pathogens--a cause for concern? The widespread use of antibiotics in food animal production systems has resulted in the emergence of antibiotic resistant zoonotic bacteria that can be transmitted to humans through the food chain. Infection with antibiotic resistant bacteria negatively impacts on public health, due to an increased incidence of treatment failure and severity of disease. Development of resistant bacteria in food animals can result from chromosomal mutations but is more commonly associated with the horizontal transfer of resistance determinants borne on mobile genetic elements. Food may represent a dynamic environment for the continuing transfer of antibiotic resistance determinants between bacteria. Current food preservation systems that use a combination of environmental stresses to reduce growth of bacteria, may serve to escalate development and dissemination of antibiotic resistance among food related pathogens. The increasing reliance on biocides for pathogen control in food production and processing, heightens the risk of selection of biocide-resistant strains. Of particular concern is the potential for sublethal exposure to biocides to select for bacteria with enhanced multi-drug efflux pump activity capable of providing both resistance to biocides and cross-resistance to multiple antibiotics. Although present evidence suggests that biocide resistance is associated with a physiological cost, the possibility of the development of adaptive mutations conferring increased fitness cannot be ruled-out. Strategies aimed at inhibiting efflux pumps and eliminating plasmids could help to restore therapeutic efficacy to antibiotics and reduce the spread of antibiotic resistant foodborne pathogens through the food chain. | 2008 | 18781926 |
| 9434 | 15 | 0.9998 | Facilitation of horizontal transfer of antimicrobial resistance by transformation of antibiotic-induced cell-wall-deficient bacteria. It is universally accepted that the use of antibiotics will lead to antimicrobial resistance. Traditionally, the explanation to this phenomenon was random mutation and horizontal gene transfer and amplification by selective pressure. Subsequently, a second mechanism of antibiotic-induced antimicrobial resistance acquisition was proposed, when Davies et al. discovered that genes encoding antimicrobial resistance are present in bacteria that produce antibiotics, and during the process of antibiotic purification from these antibiotic-producing organisms, remnants of the organisms' DNA that contain antibiotic resistance genes are also co-extracted, and can be recovered in antibiotic preparations. In addition to selective pressure and antimicrobial resistance genes in antibiotic preparations, we hypothesize the third mechanism by which administration of antibiotics leads to antimicrobial resistance. beta-Lactams and glycopeptides damage bacteria by inhibiting cell wall murein synthesis. During the process, cell-wall-deficient forms are generated before the bacteria die. These cell-wall-deficient forms have an increased ability to uptake DNA by transformation. It has been demonstrated that plasmids encoding antimicrobial resistance of Staphylococcus aureus can be transformed to Bacillus subtilis after the B. subtilis was treated with penicillin or lysostaphin, a chemical that damage the cell walls of some Gram-positive bacteria; and that short treatment of Escherichia coli with antibiotics disturbing bacterial cell wall synthesis rendered the cells capable of absorbing foreign DNA. Since bacteria occupying the same ecological niche, such as the lower gastrointestinal tract, is common, bacteria are often incubated with foreign DNA encoding resistance coming from the administration of antibiotics or other bacteria that undergone lysis unrelated to antibiotic-induced killing. As few as a single antibiotic resistant gene is taken up by the cell-wall-deficient form, it will develop into a resistant clone, despite most of the other bacteria are killed by the antibiotic. If the hypothesis is correct, one should reduce the use of antibiotics that perturb bacterial cell wall synthesis, such as beta-lactams, which is the largest group being manufactured, in both humans and animals, in order to reduce the acquisition of antibiotic resistance through this mechanism. In contrast to the old theory that antibiotics only provide selective pressures for the development of antimicrobial resistance, antibiotics by themselves are able to generate the whole chain of events towards the development of antimicrobial resistance. Antibiotics provide a source of antimicrobial resistance genes, facilitate the horizontal transfer of antimicrobial resistance genes through facilitating transformation, and provide selective pressures for amplification of the antimicrobial resistance genes. That is perhaps an important reason why antimicrobial resistance is so difficult to control. Further experiments should be performed to delineate which particular type of beta-lactam antibiotics are associated with increase in transformation efficiencies more than the others, so that we can select those less resistance generating beta-lactam for routine usage. | 2003 | 13679020 |
| 9262 | 16 | 0.9998 | Effect of chemotherapeutic agents on natural transformation frequency in Acinetobacter baylyi. Natural transformation is the ability of a bacterial cell to take up extracellular DNA which is subsequently available for recombination into the chromosome (or maintenance as an extrachromosomal element). Like other mechanisms of horizontal gene transfer, natural transformation is a significant driver for the dissemination of antimicrobial resistance. Recent studies have shown that many pharmaceutical compounds such as antidepressants and anti-inflammatory drugs can upregulate transformation frequency in the model species Acinetobacter baylyi. Chemotherapeutic compounds have been shown to increase the abundance of antimicrobial resistance genes and increase colonization rates of potentially pathogenic bacteria in patient gastrointestinal tracts, indicating an increased risk of infection and providing a pool of pathogenicity or resistance genes for transformable commensal bacteria. We here test for the effect of six cancer chemotherapeutic compounds on A. baylyi natural transformation frequency, finding two compounds, docetaxel and daunorubicin, to significantly decrease transformation frequency, and daunorubicin to also decrease growth rate significantly. Enhancing our understanding of the effect of chemotherapeutic compounds on the frequency of natural transformation could aid in preventing the horizontal spread of antimicrobial resistance genes. | 2024 | 39135654 |
| 4238 | 17 | 0.9998 | Biocide tolerance in bacteria. Biocides have been employed for centuries, so today a wide range of compounds showing different levels of antimicrobial activity have become available. At the present time, understanding the mechanisms of action of biocides has also become an important issue with the emergence of bacterial tolerance to biocides and the suggestion that biocide and antibiotic resistance in bacteria might be linked. While most of the mechanisms providing antibiotic resistance are agent specific, providing resistance to a single antimicrobial or class of antimicrobial, there are currently numerous examples of efflux systems that accommodate and, thus, provide tolerance to a broad range of structurally unrelated antimicrobials, both antibiotics and biocides. If biocide tolerance becomes increasingly common and it is linked to antibiotic resistance, not only resistant (even multi-resistant) bacteria could be passed along the food chain, but also there are resistance determinants that can spread and lead to the emergence of new resistant microorganisms, which can only be detected and monitored when the building blocks of resistance traits are understood on the molecular level. This review summarizes the main advances reached in understanding the mechanism of action of biocides, the mechanisms of bacterial resistance to both biocides and antibiotics, and the incidence of biocide tolerance in bacteria of concern to human health and the food industry. | 2013 | 23340387 |
| 9510 | 18 | 0.9998 | The Role of Efflux Pumps in the Transition from Low-Level to Clinical Antibiotic Resistance. Antibiotic resistance is on the rise and has become one of the biggest public health challenges of our time. Bacteria are able to adapt to the selective pressure exerted by antibiotics in numerous ways, including the (over)expression of efflux pumps, which represents an ancient bacterial defense mechanism. Several studies show that overexpression of efflux pumps rarely provides clinical resistance but contributes to a low-level resistance, which allows the bacteria to persist at the infection site. Furthermore, recent studies show that efflux pumps, apart from pumping out toxic substances, are also linked to persister formation and increased spontaneous mutation rates, both of which could aid persistence at the infection site. Surviving at the infection site provides the low-level-resistant population an opportunity to evolve by acquiring secondary mutations in antibiotic target genes, resulting in clinical resistance to the treating antibiotic. Thus, this emphasizes the importance and challenge for clinicians to be able to monitor overexpression of efflux pumps before low-level resistance develops to clinical resistance. One possible treatment option could be an efflux pump-targeted approach using efflux pump inhibitors. | 2020 | 33266054 |
| 4068 | 19 | 0.9998 | Co-selection for antibiotic resistance by environmental contaminants. The environment is increasingly recognised as a hotspot for the selection and dissemination of antibiotic resistant bacteria and antibiotic resistance genes. These can be selected for by antibiotics and non-antibiotic agents (such as metals and biocides), with the evidence to support this well established by observational and experimental studies. However, there is emerging evidence to suggest that plant protection products (such as herbicides), and non-antibiotic drugs (such as chemotherapeutic agents), can also co-select for antibiotic resistance. This review aims to provide an overview of four classes of non-antibiotic agents (metals, biocides, plant protection products, and non-antibiotic drugs) and how they may co-select for antibiotic resistance, with a particular focus on the environment. It also aims to identify key knowledge gaps that should be addressed in future work, to better understand these potential co-selective agents. | 2024 | 39843965 |