# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 9800 | 0 | 1.0000 | Regulation of beta-lactamase induction in gram-negative bacteria: a key to understanding the resistance puzzle. Infections caused by drug-resistant microorganisms have posed a medical challenge since the advent of antimicrobial therapy. With the emergence of resistant strains, new antibiotics were available and introduced with great success until this decade. The appearance of multiresistant microorganisms pose a real and immediate public health concern. Are we entering into the post-antibiotic era? Will we return to pre-antimicrobial-era conditions, with morbidity and mortality resulting from untreatable infectious complications? The race to stay ahead of multiresistance involves not only continued drug development and selective use but elucidation of bacterial regulation of resistance. One way to ensure continued success of antimicrobial therapy is the identification of new bacterial targets--genes and their products involved in regulating or mediating resistance. Discussion will focus on one well-defined resistance mechanism in Gram-negative bacteria, the chromosomally located amp operon, responsible for one mechanism of beta-lactam resistance. | 1994 | 7723996 |
| 9801 | 1 | 0.9999 | Problems and changing patterns of resistance with gram-negative bacteria. Throughout the antibiotic era, the emergence of drug-resistant bacteria has paralleled the development of new antimicrobial agents. As a result of selection pressures and invasive techniques that prolong the lives of seriously ill hospital patients, gram-negative bacilli have become the dominant causes of nosocomial infection. These microorganisms produce a diversity of antibiotic-inactivating enzymes. Moreover, the cell envelope of gram-negative bacteria provides a series of barriers that keep antibiotics from reaching their targets. Resistance factors can be transmitted among bacteria of different genera and species, thus conferring multidrug resistance. These problems continue to challenge scientists to better understand resistance mechanisms and to develop new compounds to circumvent them. | 1985 | 3909311 |
| 9805 | 2 | 0.9999 | Molecular mechanisms of multidrug resistance in clinically relevant enteropathogenic bacteria (Review). Multidrug resistant (MDR) enteropathogenic bacteria are a growing problem within the clinical environment due to their acquired tolerance to a wide range of antibiotics, thus causing severe illnesses and a tremendous economic impact in the healthcare sector. Due to its difficult treatment, knowledge and understanding of the molecular mechanisms that confer this resistance are needed. The aim of the present review is to describe the mechanisms of antibiotic resistance from a genomic perspective observed in bacteria, including naturally acquired resistance. The present review also discusses common pharmacological and alternative treatments used in cases of infection caused by MDR bacteria, thus covering necessary information for the development of novel antimicrobials and adjuvant molecules inhibiting bacterial proliferation. | 2022 | 36561977 |
| 9799 | 3 | 0.9999 | Microbiology and drug resistance mechanisms of fully resistant pathogens. The acquisition of vancomycin resistance by Gram-positive bacteria and carbapenem resistance by Gram-negative bacteria has rendered some hospital-acquired pathogens impossible to treat. The resistance mechanisms employed are sophisticated and very difficult to overcome. Unless alternative treatment regimes are initiated soon, our inability to treat totally resistant bacteria will halt other developments in medicine. In the community, Gram-positive bacteria responsible for pneumonia could become totally resistant leading to increased mortality from this common infection, which would have a more immediate impact on our current lifestyles. | 2004 | 15451497 |
| 4249 | 4 | 0.9999 | Detection of essential genes in Streptococcus pneumoniae using bioinformatics and allelic replacement mutagenesis. Although the emergence and spread of antimicrobial resistance in major bacterial pathogens for the past decades poses a growing challenge to public health, discovery of novel antimicrobial agents from natural products or modification of existing antibiotics cannot circumvent the problem of antimicrobial resistance. The recent development of bacterial genomics and the availability of genome sequences allow the identification of potentially novel antimicrobial agents. The cellular targets of new antimicrobial agents must be essential for the growth, replication, or survival of the bacterium. Conserved genes among different bacterial genomes often turn out to be essential (1, 2). Thus, the combination of comparative genomics and the gene knock-out procedure can provide effective ways to identify the essential genes of bacterial pathogens (3). Identification of essential genes in bacteria may be utilized for the development of new antimicrobial agents because common essential genes in diverse pathogens could constitute novel targets for broad-spectrum antimicrobial agents. | 2008 | 18392984 |
| 4253 | 5 | 0.9999 | Molecular mechanisms of polymyxin resistance and detection of mcr genes. Antibiotic resistance is an ever-increasing global problem. Major commercial antibiotics often fail to fight common bacteria, and some pathogens have become multi-resistant. Polymyxins are potent bactericidal antibiotics against gram-negative bacteria. Known resistance to polymyxin includes intrinsic, mutational and adaptive mechanisms, with the recently described horizontally acquired resistance mechanisms. In this review, we present several strategies for bacteria to develop enhanced resistance to polymyxins, focusing on changes in the outer membrane, efflux and other resistance determinants. Better understanding of the genes involved in polymyxin resistance may pave the way for the development of new and effective antimicrobial agents. We also report novel in silico tested primers for PCR assay that may be able distinguish colistin-resistant isolates carrying the plasmid-encoded mcr genes and will assist in combating the spread of colistin resistance in bacteria. | 2019 | 30439931 |
| 9806 | 6 | 0.9999 | Resistance of Gram-Positive Bacteria to Current Antibacterial Agents and Overcoming Approaches. The discovery of antibiotics has created a turning point in medical interventions to pathogenic infections, but unfortunately, each discovery was consistently followed by the emergence of resistance. The rise of multidrug-resistant bacteria has generated a great challenge to treat infections caused by bacteria with the available antibiotics. Today, research is active in finding new treatments for multidrug-resistant pathogens. In a step to guide the efforts, the WHO has published a list of the most dangerous bacteria that are resistant to current treatments and requires the development of new antibiotics for combating the resistance. Among the list are various Gram-positive bacteria that are responsible for serious healthcare and community-associated infections. Methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and drug-resistant Streptococcus pneumoniae are of particular concern. The resistance of bacteria is an evolving phenomenon that arises from genetic mutations and/or acquired genomes. Thus, antimicrobial resistance demands continuous efforts to create strategies to combat this problem and optimize the use of antibiotics. This article aims to provide a review of the most critical resistant Gram-positive bacterial pathogens, their mechanisms of resistance, and the new treatments and approaches reported to circumvent this problem. | 2020 | 32586045 |
| 4245 | 7 | 0.9999 | Antimicrobial Resistance in Bacteria: Mechanisms, Evolution, and Persistence. In recent years, we have seen antimicrobial resistance rapidly emerge at a global scale and spread from one country to the other faster than previously thought. Superbugs and multidrug-resistant bacteria are endemic in many parts of the world. There is no question that the widespread use, overuse, and misuse of antimicrobials during the last 80 years have been associated with the explosion of antimicrobial resistance. On the other hand, the molecular pathways behind the emergence of antimicrobial resistance in bacteria were present since ancient times. Some of these mechanisms are the ancestors of current resistance determinants. Evidently, there are plenty of putative resistance genes in the environment, however, we cannot yet predict which ones would be able to be expressed as phenotypes in pathogenic bacteria and cause clinical disease. In addition, in the presence of inhibitory and sub-inhibitory concentrations of antibiotics in natural habitats, one could assume that novel resistance mechanisms will arise against antimicrobial compounds. This review presents an overview of antimicrobial resistance mechanisms, and describes how these have evolved and how they continue to emerge. As antimicrobial strategies able to bypass the development of resistance are urgently needed, a better understanding of the critical factors that contribute to the persistence and spread of antimicrobial resistance may yield innovative perspectives on the design of such new therapeutic targets. | 2020 | 31659373 |
| 4247 | 8 | 0.9999 | Drug resistance in tuberculosis. Drug-resistant tuberculosis remains a worldwide problem. New laboratory methods have improved our ability to more rapidly identify resistant strains, but the most effective approach is to prevent the appearance of resistance by appropriate choice of antibiotics and directly-observed therapy. Mycobacterium tuberculosis is treated with familiar and unique drugs; consequently, mechanisms of resistance have some unique features. All drug resistance thus far identified develops by mutational events rather than acquisition of resistance genes from other bacteria. An agenda is presented for countering the appearance of further drug resistance in mycobacteria. | 1997 | 9421707 |
| 9520 | 9 | 0.9999 | Role of Natural Product in Modulation of Drug Transporters and New Delhi Metallo-β Lactamases. A rapid growth in drug resistance has brought options for treating antimicrobial resistance to a halt. Bacteria have evolved to accumulate a multitude of genes that encode resistance for a single drug within a single cell. Alternations of drug transporters are one of the causes for the development of resistance in drug interactions. Conversely, the production of enzymes also inactivates most antibiotics. The discovery of newer classes of antibiotics and drugs from natural products is urgently needed. Alternative medicines play an integral role in countries across the globe but many require validation for treatment strategies. It is essential to explore this chemical diversity in order to find novel drugs with specific activities which can be used as alternative drug targets. This review describes the interaction of drugs with resistant pathogens with a special focus on natural product-derived efflux pump and carbapenemase inhibitors. | 2019 | 30987566 |
| 9521 | 10 | 0.9999 | Next-generation strategy for treating drug resistant bacteria: Antibiotic hybrids. Resistance against nearly all antibiotics used clinically have been documented in bacteria. There is an ever-increasing danger caused by multidrug-resistant Gram-negative bacteria in both hospital and community settings. In Gram-negative bacteria, intrinsic resistance to currently available antibiotics is mainly due to overexpressed efflux pumps which are constitutively present and also presence of protective outer membrane. Combination therapy, i.e., use of two or more antibiotics, was thought to be an effective strategy because it took advantage of the additive effects of multiple antimicrobial mechanisms, lower risk of resistance development and lower mortality and improved clinical outcome. However, none of the benefits were seen in in vivo studies. Antibiotic hybrids are being used to challenge the growing drug resistance threat and increase the usefulness of current antibiotic arsenal. Antibiotic hybrids are synthetic constructs of two molecules which are covalently linked. These could be two antibiotics or antibiotic with an adjuvant (efflux pump inhibitor, siderophore, etc.) which increases the access of the antibiotics to the target. The concepts, developments and challenges in the future use of antibiotic hybrids are discussed here. Majority of the studies have been conducted on fluoroquinolones and aminoglycosides molecules. The antibiotic tobramycin has the property to enhance the action of antimicrobial agents against which the multidrug-resistant Gram-negative bacteria were earlier resistant, and thus potentiating the action of legacy antibiotics. Antibiotic hybrids may have a role as the silver bullet in Gram-negative bacteria to overcome drug resistance as well as extend the spectrum of existing antibiotics. | 2019 | 31219074 |
| 4237 | 11 | 0.9999 | Antibiotics: action and resistance in gram-negative bacteria. Therapeutic control of beta-lactamase-producing bacteria has been a major clinical problem in the past 40 years. Gram-negative bacteria are most often resistant to antibiotics as a result of the acquisition of resistant genes or gene mutation. Studies have shown that newly developed antibiotics will shortly fail to be active against the bacteria because of the emergence of resistance. Some resistant bacteria have been found to exist even before the antibiotic was developed. Selective pressure by the antibiotic is, therefore, one of the major factors to explain the increase of resistance. Recently, numerous resistant mechanisms that differ in their substrate profiles have been described at increasing frequencies. The inappropriate use of new antibiotics with extended spectrum further complicated the problem. Because resistance is a largely unavoidable consequence of widespread use of antibiotics, it is crucial that the use of drugs is selective by exercising prudent judgment and not excessive. The actual prevalence of resistance should be continuously monitored each year. Caution should be paid to the direct extrapolation of study results from other geographic areas, because the local prevalence of resistance is unlikely to be identical to those reported elsewhere. The impact of resistance to an antibiotic and its specific mechanisms, including transmissibility, should also be carefully studied. Such information may help in designing strategies for maximizing the therapeutic usefulness of drugs and minimizing the emergence of resistance. | 2002 | 11950113 |
| 9572 | 12 | 0.9999 | Diagnostic Evasion of Highly-Resistant Microorganisms: A Critical Factor in Nosocomial Outbreaks. Highly resistant microorganisms (HRMOs) may evade screening strategies used in routine diagnostics. Bacteria that have evolved to evade diagnostic tests may have a selective advantage in the nosocomial environment. Evasion of resistance detection can result from the following mechanisms: low-level expression of resistance genes not resulting in detectable resistance, slow growing variants, mimicry of wild-type-resistance, and resistance mechanisms that are only detected if induced by antibiotic pressure. We reviewed reports on hospital outbreaks in the Netherlands over the past 5 years. Remarkably, many outbreaks including major nation-wide outbreaks were caused by microorganisms able to evade resistance detection by diagnostic screening tests. We describe various examples of diagnostic evasion by several HRMOs and discuss this in a broad and international perspective. The epidemiology of hospital-associated bacteria may strongly be affected by diagnostic screening strategies. This may result in an increasing reservoir of resistance genes in hospital populations that is unnoticed. The resistance elements may horizontally transfer to hosts with systems for high-level expression, resulting in a clinically significant resistance problem. We advise to communicate the identification of HRMOs that evade diagnostics within national and regional networks. Such signaling networks may prevent inter-hospital outbreaks, and allow collaborative development of adapted diagnostic tests. | 2017 | 29163416 |
| 4241 | 13 | 0.9999 | Mechanisms of antimicrobial resistance and implications for epidemiology. The development of antibacterial agents has provided a means of treating bacterial diseases which were, previously, often fatal in both man and animal and thus represents one of the major advances of the 20th century. However, the efficacy of these agents is increasingly being compromised by the development of bacterial resistance to the drugs currently available for therapeutic use. Bacterial resistance can be combated in two ways. New drugs to which bacteria are susceptible can be developed and policies to contain the development and spread of resistance can be implemented. Both strategies require an understanding of the mechanisms of drug resistance, its epidemiology and the role of environmental factors in promoting resistance. Over the past thirty years our knowledge of bacterial resistance has increased dramatically mainly due to new technology that has become available. Bacteria are able to resist antibacterials by a variety of mechanisms: for example, altering the target to decrease susceptibility to the antibacterial, inactivating or destroying the drug, reducing drug transport into the cell or metabolic bypass. These drug resistance determinants are mediated via one of two distinct genetic mechanisms, a mutation in the bacterial chromosome or by a transmissible element; either a plasmid or a transposon. Significant differences exist between these two types of drug resistance as transmissible resistance, which is mainly plasmid-mediated, permits intraspecies and even interspecies transfer to occur. In contrast, chromosomal resistance can only be passed on to progeny. Transmissible antibacterial resistance is the major cause of concern as it can lead to the rapid spread of antibacterial resistance and has proven difficult, if not impossible, to eradicate. Furthermore, plasmids and transposons can code for multiple antibiotic resistance as well as virulence genes. Antibacterials for which transferable resistance has been identified include most commonly used antibacterials such as beta-lactams, aminoglycosides, macrolides, sulphonamides, tetracyclines, chloramphenicol and trimethoprim. One notable exception is the 4-quinolones for which plasmid-mediated resistance has yet to be identified. | 1993 | 8212509 |
| 9791 | 14 | 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 |
| 4254 | 15 | 0.9999 | The forgotten Gram-negative bacilli: what genetic determinants are telling us about the spread of antibiotic resistance. Gram-negative bacilli have become increasingly resistant to antibiotics over the past 2 decades due to selective pressure from the extensive use of antibiotics in the hospital and community. In addition, these bacteria have made optimum use of their innate genetic capabilities to extensively mutate structural and regulatory genes of antibiotic resistance factors, broadening their ability to modify or otherwise inactivate antibiotics in the cell. The great genetic plasticity of bacteria have permitted the transfer of resistance genes on plasmids and integrons between bacterial species allowing an unprecedented dissemination of genes leading to broad-spectrum resistance. As a result, many Gram-negative bacilli possess a complicated set of genes encoding efflux pumps, alterations in outer membrane lipopolysaccharides, regulation of porins and drug inactivating enzymes such as beta-lactamases, that diminish the clinical utility of today's antibiotics. The cross-species mobility of these resistance genes indicates that multidrug resistance will only increase in the future, impacting the efficacy of existing antimicrobials. This trend toward greater resistance comes at a time when very few new antibiotics have been identified capable of controlling such multi-antibiotic resistant pathogens. The continued dissemination of these resistance genes underscores the need for new classes of antibiotics that do not possess the liability of cross-resistance to existing classes of drugs and thereby having diminished potency against Gram-negative bacilli. | 2006 | 16359640 |
| 4248 | 16 | 0.9999 | Phage Display Technique: A Novel Medicinal Approach to Overcome An tibiotic Resistance by Using Peptide-Based Inhibitors Against β-Lactamases. The emergence of antibiotic resistance in bacteria is a serious threat with enormous social and economic implications. The distribution of resistance genes/markers through horizontal gene transfer leads to the dissemination of resistant strains in different parts of the world. The resistant bacteria acquire the ability to overcome resistance by different modes amongst which the expression of β-lactamases is a major factor. The β-lactamase enzymes cleave the amide bond of the β-lactam antibiotics, which constitute about one-third of the antibiotics used all over the world. In a quest to control the spread of resistant bacteria, advanced generations of antibiotics are used either alone or in combination with inhibitors. However, these antibiotics and inhibitors also contain β-lactam ring in their structure and hence are prone to be hydrolyzed by β-lactamase enzymes in the near future. Thus, the severity of the problem is manifested due to the paucity of novel non-β-lactam core containing antibiotics in the drug development stage. One approach to overcome these shortcomings is to use peptide-based inhibitors. Here, we describe the potential use of phage display technique to screen commercially available libraries to pan against β-lactamase enzymes. The main advantage of using peptide-based inhibitors is that the bacteria will not be able to recruit pre-existing defense mechanisms and it will take a long time to evolve a new mechanism in its defense against peptide-based inhibitors. | 2017 | 27465983 |
| 4244 | 17 | 0.9999 | Molecular mechanisms of antibiotic resistance. Antibiotic-resistant bacteria that are difficult or impossible to treat are becoming increasingly common and are causing a global health crisis. Antibiotic resistance is encoded by several genes, many of which can transfer between bacteria. New resistance mechanisms are constantly being described, and new genes and vectors of transmission are identified on a regular basis. This article reviews recent advances in our understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics, including the prevention of access to drug targets, changes in the structure and protection of antibiotic targets and the direct modification or inactivation of antibiotics. | 2015 | 25435309 |
| 4243 | 18 | 0.9999 | Action and resistance mechanisms of antibiotics: A guide for clinicians. Infections account for a major cause of death throughout the developing world. This is mainly due to the emergence of newer infectious agents and more specifically due to the appearance of antimicrobial resistance. With time, the bacteria have become smarter and along with it, massive imprudent usage of antibiotics in clinical practice has resulted in resistance of bacteria to antimicrobial agents. The antimicrobial resistance is recognized as a major problem in the treatment of microbial infections. The biochemical resistance mechanisms used by bacteria include the following: antibiotic inactivation, target modification, altered permeability, and "bypass" of metabolic pathway. Determination of bacterial resistance to antibiotics of all classes (phenotypes) and mutations that are responsible for bacterial resistance to antibiotics (genetic analysis) are helpful. Better understanding of the mechanisms of antibiotic resistance will help clinicians regarding usage of antibiotics in different situations. This review discusses the mechanism of action and resistance development in commonly used antimicrobials. | 2017 | 29109626 |
| 4329 | 19 | 0.9999 | Bacterial resistance: new threats, new challenges. Bacterial resistance remains a major concern. Recently, genetic transfers from saprophytic, non-pathogenic, species to pathogenic S. pneumoniae and N. meningitidis have introduced multiple changes in the penicillin target molecules, leading to rapidly growing penicillin resistance. In enterobacteriaceae, a succession of minute mutations has generated new beta-lactamases with increasingly expanded spectrum, now covering practically all available beta-lactam antibiotics. Resistance emerges in the hospital environment but also, and increasingly, in the community bacteria. Widespread resistance is probably associated with antibiotic use, abuse and misuse but direct causality links are difficult to establish. In some countries as in some hospitals, unusual resistance profiles seem to correspond to unusual antibiotic practices. For meeting the resistance challenge, no simple solutions are available, but combined efforts may help. For improving the situation, the following methods can be proposed. At the world level, a better definition of appropriate antibiotic policies should be sought, together with strong education programmes on the use of antibiotics and the control of cross-infections, plus controls on the strategies used by pharmaceutical companies for promoting antibiotics. At various local levels, accurate guidelines should be adapted to each institution and there should be regularly updated formularies using scientific, and not only economic, criteria; molecular technologies for detecting subtle epidemic variations and emergence of new genes should be developed and regular information on the resistance profiles should be available to all physicians involved in the prevention and therapy of infections. | 1993 | 8149138 |