# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 9757 | 0 | 1.0000 | Effects of different mechanisms on antimicrobial resistance in Pseudomonas aeruginosa: a strategic system for evaluating antibiotics against gram-negative bacteria. Our previous studies constructed a strategic system for testing antibiotics against specific resistance mechanisms using Klebsiella pneumoniae and Acinetobacter baumannii. However, it lacked resistance mechanisms specifically expressed only in Pseudomonas species. In this study, we constructed this system using Pseudomonas aeruginosa. In-frame deletion, site-directed mutagenesis, and plasmid transformation were used to generate genetically engineered strains with various resistance mechanisms from two fully susceptible P. aeruginosa strains. Antimicrobial susceptibility testing was used to test the efficacy of antibiotics against these strains in vitro. A total of 31 engineered strains with various antimicrobial resistance mechanisms from P. aeruginosa KPA888 and ATCC 27853 were constructed, and the same antibiotic resistance mechanism showed a similar effect on the MICs of the two strains. Compared to the parental strains, the engineered strains lacking porin OprD or lacking the regulator genes of efflux pumps all showed a ≥4-fold increase on the MICs of some of the 19 antibiotics tested. Mechanisms due to GyrA/ParC mutations and β-lactamases also contributed to their corresponding resistance as previously published. The strains constructed in this study possess well-defined resistance mechanisms and can be used to screen and evaluate the effectiveness of antibiotics against specific resistance mechanisms in P. aeruginosa. Building upon our previous studies on K. pneumoniae and A. baumannii, this strategic system, including a P. aeruginosa panel, has been expanded to cover almost all the important antibiotic resistance mechanisms of gram-negative bacteria that are in urgent need of new antibiotics.IMPORTANCEIn this study, an antibiotic assessment system for P. aeruginosa was developed, and the system can be expanded to include other key pathogens and resistance mechanisms. This system offers several benefits: (i) compound design: aid in the development of compounds that can bypass or counteract resistance mechanisms, leading to more effective treatments against specific resistant strains; (ii) combination therapies: facilitate the exploration of combination therapies, where multiple antibiotics may work synergistically to overcome resistance and enhance treatment efficacy; and (iii) targeted treatments: enable healthcare providers to prescribe more targeted treatments, reducing unnecessary antibiotic use and helping to slow the spread of antibiotic resistance. In summary, this system could streamline the development process, reduce costs, increase the success rate of new antibiotics, and help prevent and control antimicrobial resistance. | 2025 | 40042282 |
| 9756 | 1 | 0.9999 | Genomewide identification of genetic determinants of antimicrobial drug resistance in Pseudomonas aeruginosa. The emergence of antimicrobial drug resistance is of enormous public concern due to the increased risk of delayed treatment of infections, the increased length of hospital stays, the substantial increase in the cost of care, and the high risk of fatal outcomes. A prerequisite for the development of effective therapy alternatives is a detailed understanding of the diversity of bacterial mechanisms that underlie drug resistance, especially for problematic gram-negative bacteria such as Pseudomonas aeruginosa. This pathogen has impressive chromosomally encoded mechanisms of intrinsic resistance, as well as the potential to mutate, gaining resistance to current antibiotics. In this study we have screened the comprehensive nonredundant Harvard PA14 library for P. aeruginosa mutants that exhibited either increased or decreased resistance against 19 antibiotics commonly used in the clinic. This approach identified several genes whose inactivation sensitized the bacteria to a broad spectrum of different antimicrobials and uncovered novel genetic determinants of resistance to various classes of antibiotics. Knowledge of the enhancement of bacterial susceptibility to existing antibiotics and of novel resistance markers or modifiers of resistance expression may lay the foundation for effective therapy alternatives and will be the basis for the development of new strategies in the control of problematic multiresistant gram-negative bacteria. | 2009 | 19332674 |
| 4816 | 2 | 0.9999 | Sub-inhibitory concentrations of colistin and imipenem impact the expression of biofilm-associated genes in Acinetobacter baumannii. Acinetobacter baumannii is an opportunistic pathogen that is responsible for nosocomial infections. Imipenem and colistin are drugs that are commonly used to treat severe infections caused by A. baumannii, such as sepsis, ventilator-associated pneumonia, and bacteremia. However, some strains of A. baumannii have become resistant to these drugs, which is a concern for public health. Biofilms produced by A. baumannii increase their resistance to antibiotics and the cells within the inner layers of biofilm are exposed to sub-inhibitory concentrations (sub-MICs) of antibiotics. There is limited information available regarding how the genes of A. baumannii are linked to biofilm formation when the bacteria are exposed to sub-MICs of imipenem and colistin. Thus, this study's objective was to explore this relationship by examining the genes involved in biofilm formation in A. baumannii when exposed to low levels of imipenem and colistin. The study found that exposing an isolate of A. baumannii to low levels of these drugs caused changes in their drug susceptibility pattern. The relative gene expression profiles of the biofilm-associated genes exhibited a change in their expression profile during short-term and long-term exposure. This study highlights the potential consequences of overuse and misuse of antibiotics, which can help bacteria become resistant to these drugs. | 2024 | 38489041 |
| 6274 | 3 | 0.9999 | Transcriptomics Reveals How Minocycline-Colistin Synergy Overcomes Antibiotic Resistance in Multidrug-Resistant Klebsiella pneumoniae. Multidrug-resistant Gram-negative bacteria are a rapidly growing public health threat, and the development of novel antimicrobials has failed to keep pace with their emergence. Synergistic combinations of individually ineffective drugs present a potential solution, yet little is understood about the mechanisms of most such combinations. Here, we show that the combination of colistin (polymyxin E) and minocycline has a high rate of synergy against colistin-resistant and minocycline-intermediate or -resistant strains of Klebsiella pneumoniae. Furthermore, using transcriptome sequencing (RNA-Seq), we characterized the transcriptional profiles of these strains when treated with the drugs individually and in combination. We found a striking similarity between the transcriptional profiles of bacteria treated with the combination of colistin and minocycline at individually subinhibitory concentrations and those of the same isolates treated with minocycline alone. We observed a similar pattern with the combination of polymyxin B nonapeptide (a polymyxin B analogue that lacks intrinsic antimicrobial activity) and minocycline. We also found that genes involved in polymyxin resistance and peptidoglycan biosynthesis showed significant differential gene expression in the different treatment conditions, suggesting possible mechanisms for the antibacterial activity observed in the combination. These findings suggest that the synergistic activity of this combination against bacteria resistant to each drug alone involves sublethal outer membrane disruption by colistin, which permits increased intracellular accumulation of minocycline. | 2022 | 35041511 |
| 9791 | 4 | 0.9999 | Beta-lactam resistance and the effectiveness of antimicrobial peptides against KPC-producing bacteria. Bacterial resistance is a problem that is giving serious cause for concern because bacterial strains such as Acinetobacter baumannii and Pseudomonas aeruginosa are difficult to treat and highly opportunistic. These bacteria easily acquire resistance genes even from other species, which confers greater persistence and tolerance towards conventional antibiotics. These bacteria have the highest death rate in hospitalized intensive care patients, so strong measures must be taken. In this review, we focus on the use of antimicrobial peptides (AMPs) as an alternative to traditional drugs, due to their rapid action and lower risk of generating resistance by microorganisms. We also present an overview of beta-lactams and explicitly explain the activity of AMPs against carbapenemase-producing bacteria as potential alternative agents for infection control. | 2022 | 36042694 |
| 6275 | 5 | 0.9999 | Resistance to fosfomycin: Mechanisms, Frequency and Clinical Consequences. Fosfomycin has been used for the treatment of infections due to susceptible and multidrug-resistant (MDR) bacteria. It inhibits bacterial cell wall synthesis through a unique mechanism of action at a step prior to that inhibited by β-lactams. Fosfomycin enters the bacterium through membrane channels/transporters and inhibits MurA, which initiates peptidoglycan (PG) biosynthesis of the bacterial cell wall. Several bacteria display inherent resistance to fosfomycin mainly through MurA mutations. Acquired resistance involves, in order of decreasing frequency, modifications of membrane transporters that prevent fosfomycin from entering the bacterial cell, acquisition of plasmid-encoded genes that inactivate fosfomycin, and MurA mutations. Fosfomycin resistance develops readily in vitro but less so in vivo. Mutation frequency is higher among Pseudomonas aeruginosa and Klebsiella spp. compared with Escherichia coli and is associated with fosfomycin concentration. Mutations in cAMP regulators, fosfomycin transporters and MurA seem to be associated with higher biological cost in Enterobacteriaceae but not in Pseudomonas spp. The contribution of fosfomycin inactivating enzymes in emergence and spread of fosfomycin resistance currently seems low-to-moderate, but their presence in transferable plasmids may potentially provide the best means for the spread of fosfomycin resistance in the future. Their co-existence with genes conferring resistance to other antibiotic classes may increase the emergence of MDR strains. Although susceptibility rates vary, rates seem to increase in settings with higher fosfomycin use and among multidrug-resistant pathogens. | 2019 | 30268576 |
| 4832 | 6 | 0.9998 | Antibiotic resistance of Pseudomonas species. Pseudomonas species are highly versatile organisms with genetic and physiologic capabilities that allow them to flourish in environments hostile to most pathogenic bacteria. Within the lung of the patient with cystic fibrosis, exposed to a number of antimicrobial agents, highly resistant clones of Pseudomonas are selected. These may have acquired plasmid-mediated genes encoding a variety of beta-lactamases or aminoglycoside modifying enzymes. Frequently these resistance determinants are on transposable elements, facilitating their dissemination among the population of bacteria. Mutations in chromosomal genes can also occur, resulting in constitutive expression of normally repressed enzymes, such as the chromosomal cephalosporinase of Pseudomonas aeruginosa or Pseudomonas cepacia. These enzymes may confer resistance to the expanded-spectrum beta-lactam drugs. Decreased cellular permeability to the beta-lactams and the aminoglycosides also results in clinically significant antibiotic resistance. The development of new drugs with anti-Pseudomonas activity, beta-lactam agents and the quinolones, has improved the potential for effective chemotherapy but has not surpassed the potential of the organisms to develop resistance. | 1986 | 3701534 |
| 4405 | 7 | 0.9998 | Copper Resistance of the Emerging Pathogen Acinetobacter baumannii. Acinetobacter baumannii is an important emerging pathogen that is capable of causing many types of severe infection, especially in immunocompromised hosts. Since A. baumannii can rapidly acquire antibiotic resistance genes, many infections are on the verge of being untreatable, and novel therapies are desperately needed. To investigate the potential utility of copper-based antibacterial strategies against Acinetobacter infections, we characterized copper resistance in a panel of recent clinical A. baumannii isolates. Exposure to increasing concentrations of copper in liquid culture and on solid surfaces resulted in dose-dependent and strain-dependent effects; levels of copper resistance varied broadly across isolates, possibly resulting from identified genotypic variation among strains. Examination of the growth-phase-dependent effect of copper on A. baumannii revealed that resistance to copper increased dramatically in stationary phase. Moreover, A. baumannii biofilms were more resistant to copper than planktonic cells but were still susceptible to copper toxicity. Exposure of bacteria to subinhibitory concentrations of copper allowed them to better adapt to and grow in high concentrations of copper; this copper tolerance response is likely achieved via increased expression of copper resistance mechanisms. Indeed, genomic analysis revealed numerous putative copper resistance proteins that share amino acid homology to known proteins in Escherichia coli and Pseudomonas aeruginosa Transcriptional analysis revealed significant upregulation of these putative copper resistance genes following brief copper exposure. Future characterization of copper resistance mechanisms may aid in the search for novel antibiotics against Acinetobacter and other highly antibiotic-resistant pathogens. IMPORTANCE: Acinetobacter baumannii causes many types of severe nosocomial infections; unfortunately, some isolates have acquired resistance to almost every available antibiotic, and treatment options are incredibly limited. Copper is an essential nutrient but becomes toxic at high concentrations. The inherent antimicrobial properties of copper give it potential for use in novel therapeutics against drug-resistant pathogens. We show that A. baumannii clinical isolates are sensitive to copper in vitro, both in liquid and on solid metal surfaces. Since bacterial resistance to copper is mediated though mechanisms of efflux and detoxification, we identified genes encoding putative copper-related proteins in A. baumannii and showed that expression of some of these genes is regulated by the copper concentration. We propose that the antimicrobial effects of copper may be beneficial in the development of future therapeutics that target multidrug-resistant bacteria. | 2016 | 27520808 |
| 4402 | 8 | 0.9998 | Mechanisms of antimicrobial resistance in Stenotrophomonas maltophilia: a review of current knowledge. Introduction: Stenotrophomonas maltophilia is a prototype of bacteria intrinsically resistant to antibiotics. The reduced susceptibility of this microorganism to antimicrobials mainly relies on the presence in its chromosome of genes encoding efflux pumps and antibiotic inactivating enzymes. Consequently, the therapeutic options for treating S. maltophilia infections are limited.Areas covered: Known mechanisms of intrinsic, acquired and phenotypic resistance to antibiotics of S. maltophilia and the consequences of such resistance for treating S. maltophilia infections are discussed. Acquisition of some genes, mainly those involved in co-trimoxazole resistance, contributes to acquired resistance. Mutation, mainly in the regulators of chromosomally-encoded antibiotic resistance genes, is a major cause for S. maltophilia acquisition of resistance. The expression of some of these genes is triggered by specific signals or stressors, which can lead to transient phenotypic resistance.Expert opinion: Treatment of S. maltophilia infections is difficult because this organism presents low susceptibility to antibiotics. Besides, it can acquire resistance to antimicrobials currently in use. Particularly problematic is the selection of mutants overexpressing efflux pumps since they present a multidrug resistance phenotype. The use of novel antimicrobials alone or in combination, together with the development of efflux pumps' inhibitors may help in fighting S. maltophilia infections. | 2020 | 32052662 |
| 9917 | 9 | 0.9998 | Fluorescence-Based Detection of Natural Transformation in Drug-Resistant Acinetobacter baumannii. Acinetobacter baumannii is a nosocomial agent with a high propensity for developing resistance to antibiotics. This ability relies on horizontal gene transfer mechanisms occurring in the Acinetobacter genus, including natural transformation. To study natural transformation in bacteria, the most prevalent method uses selection for the acquisition of an antibiotic resistance marker in a target chromosomal locus by the recipient cell. Most clinical isolates of A. baumannii are resistant to multiple antibiotics, limiting the use of such selection-based methods. Here, we report the development of a phenotypic and selection-free method based on flow cytometry to detect transformation events in multidrug-resistant (MDR) clinical A. baumannii isolates. To this end, we engineered a translational fusion between the abundant and conserved A. baumannii nucleoprotein (HU) and the superfolder green fluorescent protein (sfGFP). The new method was benchmarked against the conventional antibiotic selection-based method. Using this new method, we investigated several parameters affecting transformation efficiencies and identified conditions of transformability one hundred times higher than those previously reported. Using optimized transformation conditions, we probed natural transformation in a set of MDR clinical and nonclinical animal A. baumannii isolates. Regardless of their origin, the majority of the isolates displayed natural transformability, indicative of a conserved trait in the species. Overall, this new method and optimized protocol will greatly facilitate the study of natural transformation in the opportunistic pathogen A. baumanniiIMPORTANCE Antibiotic resistance is a pressing global health concern with the rise of multiple and panresistant pathogens. The rapid and unfailing resistance to multiple antibiotics of the nosocomial agent Acinetobacter baumannii, notably to carbapenems, prompt to understand the mechanisms behind acquisition of new antibiotic resistance genes. Natural transformation, one of the horizontal gene transfer mechanisms in bacteria, was only recently described in A. baumannii and could explain its ability to acquire resistance genes. We developed a reliable method to probe and study natural transformation mechanism in A. baumannii More broadly, this new method based on flow cytometry will allow experimental detection and quantification of horizontal gene transfer events in multidrug-resistant A. baumannii. | 2018 | 30012729 |
| 4408 | 10 | 0.9998 | Multidrug resistant Acinetobacter baumannii--the role of AdeABC (RND family) efflux pump in resistance to antibiotics. Acinetobacter baumannii is an opportunistic pathogen which play the more and more greater role in the pathogenicity of the human. It is often attached with the hospital environment, in which is able easily to survive for many days even in adverse conditions. Acinetobacter baumannii is the species responsible for a serious nosocomial infections, especially in the intensive care units. Option of surviving in natural niches, and in the hospital environment could also be associated with the efflux pump mechanisms. Mechanisms of efflux universally appear in all cells (eukaryotic and prokaryotic) and play the physiological important role. In prokaryote, the main functions are evasion of such naturally produced molecules, removal of metabolic products and toxins. These pumps could also be involved in an early stage of infection, such as adhesion to host cells and the colonization. Importantly, they remove commonly used antibiotics from the cell in therapy of infections caused by these bacteria. Efflux pumps exemplify a unique phenomenon in drug resistance: a single mechanism causing resistance against several different classes of antibiotics. In Acinetobacter baumannii, the AdeABC efflux pump, a member of the resistance-nodulation-cell division family (RND), has been well characterized. Aminoglicosides, tetracyclines, erythromycin, chloramphenicol, trimethoprim, fluoroquinolones, some beta-lactams, and also recently tigecycline, were found to be substrates for this pump. Drugs, as substrates for the AdeABC pump, can increase the expression of the AdeABC genes, leading to multidrug resistance (MDR). From this reason, treatment failure and death caused by Acinetobacter baumannii infections or underlying diseases are common. Because the AdeABC pump is widespread in Acinetobacter baumannii, similarly to other pumps in Gram-negative and Gram-positive bacteria, exists a need of searching a new therapeutic solutions. Specific efflux inhibitors of pumps (EPIs), including AdeABC inhibitors, could be suppress the activity of pumps and restore the sensitivity of such important bacteria as Acinetobacter baumannii to commonly used antibiotic. | 2008 | 19056528 |
| 9921 | 11 | 0.9998 | Identification of Multiple Low-Level Resistance Determinants and Coselection of Motility Impairment upon Sub-MIC Ceftriaxone Exposure in Escherichia coli. Resistance to third-generation cephalosporins among Gram-negative bacteria is a rapidly growing public health threat. Among the most commonly used third-generation cephalosporins is ceftriaxone. Bacterial exposure to sublethal or sub-MIC antibiotic concentrations occurs widely, from environmental residues to intermittently at the site of infection. Quality of ceftriaxone is also a concern, especially in low- and middle-income countries, with medicines having inappropriate active pharmaceutical ingredient (API) content or concentration. While focus has been largely on extended-spectrum β-lactamases and high-level resistance, there are limited data on specific chromosomal mutations and other pathways that contribute to ceftriaxone resistance under these conditions. In this work, Escherichia coli cells were exposed to a broad range of sub-MICs of ceftriaxone and mutants were analyzed using whole-genome sequencing. Low-level ceftriaxone resistance emerged after as low as 10% MIC exposure, with the frequency of resistance development increasing with concentration. Genomic analyses of mutants revealed multiple genetic bases. Mutations were enriched in genes associated with porins (envZ, ompF, ompC, and ompR), efflux regulation (marR), and the outer membrane and metabolism (galU and pgm), but none were associated with the ampC β-lactamase. We also observed selection of mgrB mutations. Notably, pleiotropic effects on motility and cell surface were selected for in multiple independent genes, which may have important consequences. Swift low-level resistance development after exposure to low ceftriaxone concentrations may result in reservoirs of bacteria with relevant mutations for survival and increased resistance. Thus, initiatives for broader surveillance of low-level antibiotic resistance and genomic resistance determinants should be pursued when resources are available. IMPORTANCE Ceftriaxone is a widely consumed antibiotic used to treat bacterial infections. Bacteria, however, are increasingly becoming resistant to ceftriaxone. Most work has focused on known mechanisms associated with high-level ceftriaxone resistance. However, bacteria are extensively exposed to low antibiotic concentrations, and there are limited data on the evolution of ceftriaxone resistance under these conditions. In this work, we observed that bacteria quickly developed low-level resistance due to both novel and previously described mutations in multiple different genes upon exposure to low ceftriaxone concentrations. Additionally, exposure also led to changes in motility and the cell surface, which can impact other processes associated with resistance and infection. Notably, low-level-resistant bacteria would be missed in the clinic, which uses set breakpoints. While they may require increased resources, this work supports continued initiatives for broader surveillance of low-level antibiotic resistance or their resistance determinants, which can serve as predictors of higher risk for clinical resistance. | 2021 | 34787446 |
| 9755 | 12 | 0.9998 | Phages for treatment Pseudomonas aeruginosa infection. Pseudomonas aeruginosa is denoted as one of the highly threatening bacteria to the public health. It has acquired many virulent factors and resistant genes that make it difficult to control with conventional antibiotics. Thus, bacteriophage therapy (phage therapy) is a proposed alternative to antibiotics to fight against multidrug-resistant P. aeruginosa. Many phages have been isolated that exhibit a broad spectrum of activity against P. aeruginosa. In this chapter, the common virulent factors and the prevalence of antibiotic-resistance genes in P. aeruginosa were reported. In addition, recent efforts in the field of phage therapy against P. aeruginosa were highlighted, including wild-type phages, genetically modified phages, phage cocktails, and phage in combination with antibiotics against P. aeruginosa in the planktonic and biofilm forms. Recent regulations on phage therapy were also covered in this chapter. | 2023 | 37770166 |
| 9922 | 13 | 0.9998 | De novo acquisition of antibiotic resistance in six species of bacteria. Bacteria can become resistant to antibiotics in two ways: by acquiring resistance genes through horizontal gene transfer and by de novo development of resistance upon exposure to non-lethal concentrations. The importance of the second process, de novo build-up, has not been investigated systematically over a range of species and may be underestimated as a result. To investigate the DNA mutation patterns accompanying the de novo antibiotic resistance acquisition process, six bacterial species encountered in the food chain were exposed to step-wise increasing sublethal concentrations of six antibiotics to develop high levels of resistance. Phenotypic and mutational landscapes were constructed based on whole-genome sequencing at two time points of the evolutionary trajectory. In this study, we found that (1) all of the six strains can develop high levels of resistance against most antibiotics; (2) increased resistance is accompanied by different mutations for each bacterium-antibiotic combination; (3) the number of mutations varies widely, with Y. enterocolitica having by far the most; (4) in the case of fluoroquinolone resistance, a mutational pattern of gyrA combined with parC is conserved in five of six species; and (5) mutations in genes coding for efflux pumps are widely encountered in gram-negative species. The overall conclusion is that very similar phenotypic outcomes are instigated by very different genetic changes. The outcome of this study may assist policymakers when formulating practical strategies to prevent development of antimicrobial resistance in human and veterinary health care.IMPORTANCEMost studies on de novo development of antimicrobial resistance have been performed on Escherichia coli. To examine whether the conclusions of this research can be applied to more bacterial species, six species of veterinary importance were made resistant to six antibiotics, each of a different class. The rapid build-up of resistance observed in all six species upon exposure to non-lethal concentrations of antimicrobials indicates a similar ability to adjust to the presence of antibiotics. The large differences in the number of DNA mutations accompanying de novo resistance suggest that the mechanisms and pathways involved may differ. Hence, very similar phenotypes can be the result of various genotypes. The implications of the outcome are to be considered by policymakers in the area of veterinary and human healthcare. | 2025 | 39907470 |
| 8857 | 14 | 0.9998 | Colistin-phage combinations decrease antibiotic resistance in Acinetobacter baumannii via changes in envelope architecture. Multidrug-resistant bacterial infections are becoming increasingly common, with only few last-resort antibiotics such as colistin available for clinical therapy. An alternative therapeutic strategy gaining momentum is phage therapy, which has the advantage of not being affected by bacterial resistance to antibiotics. However, a major challenge in phage therapy is the rapid emergence of phage-resistant bacteria. In this work, our main aim was to understand the mechanisms of phage-resistance used by the top priority pathogen Acinetobacter baumannii. We isolated the novel phage Phab24, capable of infecting colistin-sensitive and -resistant strains of A. baumannii. After co-incubating Phab24 with its hosts, we obtained phage-resistant mutants which were characterized on both genotypic and phenotypic levels. Using whole genome sequencing, we identified phage-resistant strains that displayed mutations in genes that alter the architecture of the bacterial envelope at two levels: the capsule and the outer membrane. Using an adsorption assay, we confirmed that phage Phab24 uses the bacterial capsule as its primary receptor, with the outer membrane possibly serving as the secondary receptor. Interestingly, the phage-resistant isolates were less virulent compared to the parental strains in a Galleria mellonella infection model. Most importantly, we observed that phage-resistant bacteria that evolved in the absence of antibiotics exhibited an increased sensitivity to colistin, even though the antibiotic resistance mechanism per se remained unaltered. This increase in antibiotic sensitivity is a direct consequence of the phage-resistance mechanism, and could potentially be exploited in the clinical setting. | 2021 | 34736365 |
| 4833 | 15 | 0.9998 | Emerging mechanisms of fluoroquinolone resistance. Broad use of fluoroquinolones has been followed by emergence of resistance, which has been due mainly to chromosomal mutations in genes encoding the subunits of the drugs' target enzymes, DNA gyrase and topoisomerase IV, and in genes that affect the expression of diffusion channels in the outer membrane and multidrug-resistance efflux systems. Resistance emerged first in species in which single mutations were sufficient to cause clinically important levels of resistance (e.g., Staphylococcus aureus and Pseudomonas aeruginosa). Subsequently, however, resistance has emerged in bacteria such as Campylobacter jejuni, Escherichia coli, and Neisseria gonorrhoeae, in which multiple mutations are required to generate clinically important resistance. In these circumstances, the additional epidemiologic factors of drug use in animals and human-to-human spread appear to have contributed. Resistance in Streptococcus pneumoniae, which is currently low, will require close monitoring as fluoroquinolones are used more extensively for treating respiratory tract infections. | 2001 | 11294736 |
| 9754 | 16 | 0.9998 | The Resilience of Pseudomonas aeruginosa to Antibiotics and the Designing of Antimicrobial Peptides to Overcome Microbial Resistance. Pseudomonas aeruginosa (P. aeruginosa) is a bacterium of medical concern known for its potential to persist in diverse environments due to its metabolic capacity. Its survival ability is linked to its relatively large genome of 5.5-7 Mbp, from which several genes are employed in overcoming conventional antibiotic treatments and promoting resistance. The worldwide prevalence of antibiotic-resistant clones of P. aeruginosa necessitates novel approaches to researching their multiple resistance mechanisms, such as the use of antimicrobial peptides (AMPs). In this review, we briefly discuss the epidemiology of the resistant strains of P. aeruginosa and then describe their resistance mechanisms. Next, we explain the biology of AMPs, enlist the present database platforms that describe AMPs, and discuss their usefulness and limitations in treating P. aeruginosa strains. Finally, we present 13 AMPs with theoretical action against P. aeruginosa, all of which we evaluated in silico in this work. Our results suggest that the AMPs we evaluated have a carpet-like mode of action with a membranolytic function in Gram-positive and Gramnegative bacteria, with a clear potential of synthesis for in vitro evaluation. | 2022 | 36082872 |
| 4429 | 17 | 0.9998 | General mechanisms of resistance to antibiotics. Resistance to antimicrobial agents may result from intrinsic properties of organisms, through mutation and through plasmid- and transposon-specified genes. beta-Lactam resistance is most frequently associated with one or more chromosomal- or plasmid-specified beta-lactamases. Recently, mutations modifying penicillin-binding proteins have been detected with increased frequency as a cause of beta-lactam resistance. Mixed mechanisms, reduced permeability and tolerance are other causes of resistance. Aminoglycoside resistance always involves some modification of drug uptake, most often due to a variety of enzymes modifying these compounds. Reduced uptake is a primary cause of resistance in anaerobic bacteria and bacteria growing anaerobically, some strains of Pseudomonas aeruginosa, and mutants that arise during antimicrobial therapy and are defective in energy-generation systems. Resistance to other antimicrobial agents is presented in tabular form. | 1988 | 3062000 |
| 4252 | 18 | 0.9998 | Extreme antimicrobial peptide and polymyxin B resistance in the genus Burkholderia. Cationic antimicrobial peptides and polymyxins are a group of naturally occurring antibiotics that can also possess immunomodulatory activities. They are considered a new source of antibiotics for treating infections by bacteria that are resistant to conventional antibiotics. Members of the genus Burkholderia, which includes various human pathogens, are inherently resistant to antimicrobial peptides. The resistance is several orders of magnitude higher than that of other Gram-negative bacteria such as Escherichia coli, Salmonella enterica, or Pseudomonas aeruginosa. This review summarizes our current understanding of antimicrobial peptide and polymyxin B resistance in the genus Burkholderia. These bacteria possess major and minor resistance mechanisms that will be described in detail. Recent studies have revealed that many other emerging Gram-negative opportunistic pathogens may also be inherently resistant to antimicrobial peptides and polymyxins and we propose that Burkholderia sp. are a model system to investigate the molecular basis of the resistance in extremely resistant bacteria. Understanding resistance in these types of bacteria will be important if antimicrobial peptides come to be used regularly for the treatment of infections by susceptible bacteria because this may lead to increased resistance in the species that are currently susceptible and may also open up new niches for opportunistic pathogens with high inherent resistance. | 2011 | 22919572 |
| 4251 | 19 | 0.9998 | Extreme antimicrobial Peptide and polymyxin B resistance in the genus burkholderia. Cationic antimicrobial peptides and polymyxins are a group of naturally occurring antibiotics that can also possess immunomodulatory activities. They are considered a new source of antibiotics for treating infections by bacteria that are resistant to conventional antibiotics. Members of the genus Burkholderia, which includes various human pathogens, are inherently resistant to antimicrobial peptides. The resistance is several orders of magnitude higher than that of other Gram-negative bacteria such as Escherichia coli, Salmonella enterica, or Pseudomonas aeruginosa. This review summarizes our current understanding of antimicrobial peptide and polymyxin B resistance in the genus Burkholderia. These bacteria possess major and minor resistance mechanisms that will be described in detail. Recent studies have revealed that many other emerging Gram-negative opportunistic pathogens may also be inherently resistant to antimicrobial peptides and polymyxins and we propose that Burkholderia sp. are a model system to investigate the molecular basis of the resistance in extremely resistant bacteria. Understanding resistance in these types of bacteria will be important if antimicrobial peptides come to be used regularly for the treatment of infections by susceptible bacteria because this may lead to increased resistance in the species that are currently susceptible and may also open up new niches for opportunistic pathogens with high inherent resistance. | 2011 | 21811491 |