# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 395 | 0 | 0.9905 | O-antigen protects gram-negative bacteria from histone killing. Beyond their traditional role of wrapping DNA, histones display antibacterial activity to Gram-negative and -positive bacteria. To identify bacterial components that allow survival to a histone challenge, we selected resistant bacteria from homologous Escherichia coli libraries that harbor plasmids carrying pieces of the chromosome in different sizes. We identified genes required for exopolysaccharide production and for the synthesis of the polysaccharide domain of the lipopolysaccharide, called O-antigen. Indeed, O-antigen and exopolysaccharide conferred further resistance to histones. Notably, O-antigen also conferred resistance to histones in the pathogens Shigella flexneri and Klebsiella pneumoniae. | 2013 | 23951089 |
| 3766 | 1 | 0.9905 | Identification of Genome-Wide Mutations in Ciprofloxacin-Resistant F. tularensis LVS Using Whole Genome Tiling Arrays and Next Generation Sequencing. Francisella tularensis is classified as a Class A bioterrorism agent by the U.S. government due to its high virulence and the ease with which it can be spread as an aerosol. It is a facultative intracellular pathogen and the causative agent of tularemia. Ciprofloxacin (Cipro) is a broad spectrum antibiotic effective against Gram-positive and Gram-negative bacteria. Increased Cipro resistance in pathogenic microbes is of serious concern when considering options for medical treatment of bacterial infections. Identification of genes and loci that are associated with Ciprofloxacin resistance will help advance the understanding of resistance mechanisms and may, in the future, provide better treatment options for patients. It may also provide information for development of assays that can rapidly identify Cipro-resistant isolates of this pathogen. In this study, we selected a large number of F. tularensis live vaccine strain (LVS) isolates that survived in progressively higher Ciprofloxacin concentrations, screened the isolates using a whole genome F. tularensis LVS tiling microarray and Illumina sequencing, and identified both known and novel mutations associated with resistance. Genes containing mutations encode DNA gyrase subunit A, a hypothetical protein, an asparagine synthase, a sugar transamine/perosamine synthetase and others. Structural modeling performed on these proteins provides insights into the potential function of these proteins and how they might contribute to Cipro resistance mechanisms. | 2016 | 27668749 |
| 9925 | 2 | 0.9901 | Plasmid-mediated quinolone resistance--current knowledge and future perspectives. Quinolones are a group of antimicrobial agents that were serendipitously discovered as byproducts of the synthesis of chloroquine. Chemical modifications, such as the addition of fluorine or piperazine, resulted in the synthesis of third- and fourth-generation fluoroquinolones, with broad-spectrum antimicrobial actions against aerobic or anaerobic, Gram-positive or Gram-negative bacteria. The efficacy and consequent widespread use of quinolones and fluoroquinolones has led to a steady global increase in resistance, mediated via gene mutations, alterations in efflux or cell membranes and plasmid-conferred resistance. The first plasmid-mediated quinolone resistance gene, qnrA1, was detected in 1998. Since then, many other genes have been identified and the underlying mechanisms of resistance have been elucidated. This review provides an overview of quinolone resistance, with particular emphasis on plasmid-mediated resistance. | 2013 | 23569126 |
| 9785 | 3 | 0.9900 | Mis-annotations of a promising antibiotic target in high-priority gram-negative pathogens. The rise of antibiotic resistance combined with the lack of new products entering the market has led to bacterial infections becoming one of the biggest threats to global health. Therefore, there is an urgent need to identify novel antibiotic targets, such as dihydrodipicolinate synthase (DHDPS), an enzyme involved in the production of essential metabolites in cell wall and protein synthesis. Here, we utilised a 7-residue sequence motif to identify mis-annotation of multiple DHDPS genes in the high-priority Gram-negative bacteria Acinetobacter baumannii and Klebsiella pneumoniae. We subsequently confirmed these mis-annotations using a combination of enzyme kinetics and X-ray crystallography. Thus, this study highlights the need to ensure genes encoding promising drug targets, like DHDPS, are annotated correctly, especially for clinically important pathogens. PDB ID: 6UE0. | 2020 | 31943170 |
| 9926 | 4 | 0.9900 | beta-Lactamases of gram-negative bacteria: new challenges for new drugs. The major emphasis in new drug design within the beta-lactam family has been on compounds less susceptible to hydrolysis by beta-lactamases and on combinations containing an enzyme-labile drug plus a beta-lactamase inhibitor. The introduction of such new compounds into clinical use has been followed by the discovery of novel mechanisms of resistance among gram-negative bacteria. These include the appearance of new enzymes, many of which are derivatives of older beta-lactamases. In addition, genes for certain broad-spectrum enzymes previously restricted to chromosomal sites have moved onto plasmids. There is now a greater appreciation of how alterations in enzyme expression--either alone or in concert with changes in drug permeation--can also lead to resistance. Clearly, recent events in the development of new beta-lactam agents have led to a new phase in the understanding of beta-lactam resistance. | 1992 | 1600011 |
| 799 | 5 | 0.9900 | An ace up their sleeve: a transcriptomic approach exposes the AceI efflux protein of Acinetobacter baumannii and reveals the drug efflux potential hidden in many microbial pathogens. The era of antibiotics as a cure-all for bacterial infections appears to be coming to an end. The emergence of multidrug resistance in many hospital-associated pathogens has resulted in "superbugs" that are effectively untreatable. Multidrug efflux pumps are well known mediators of bacterial drug resistance. Genome sequencing efforts have highlighted an abundance of putative efflux pump genes in bacteria. However, it is not clear how many of these pumps play a role in antimicrobial resistance. Efflux pump genes that participate in drug resistance can be under tight regulatory control and expressed only in response to substrates. Consequently, changes in gene expression following antimicrobial shock may be used to identify efflux pumps that mediate antimicrobial resistance. Using this approach we have characterized several novel efflux pumps in bacteria. In one example we recently identified the Acinetobacterchlorhexidine efflux protein (AceI) efflux pump in Acinetobacter. AceI is a prototype for a novel family of multidrug efflux pumps conserved in many proteobacterial lineages. The discovery of this family raises the possibility that additional undiscovered intrinsic resistance proteins may be encoded in the core genomes of pathogenic bacteria. | 2015 | 25954261 |
| 9924 | 6 | 0.9900 | Molecular mechanisms of fluoroquinolone resistance. Fluoroquinolones have a broad spectrum of activity for complicated urinary tract infections, gastrointestinal infections, respiratory tract infections, sexually transmitted diseases, and chronic osteomyelitis. Since fluoroquinolones are excellent antibiotics for a number of clinical indications, their consumption has increased rapidly, both in human medicine and in food animals. Resistance to fluoroquinolones is chromosomal mediated, involving mutations either in the target genes including DNA gyrase (gyrA or gyrB) and topoisomerase IV (parC or parE), or in the regulatory factors controlling bacterial permeability or the efflux capacity of the bacteria. This review focuses on mechanisms of fluoroquinolone resistance, including known and proposed molecular mechanisms. This review also discuses the clinical impact of fluoroquinolone-resistant bacteria. | 2003 | 12741725 |
| 9812 | 7 | 0.9899 | Drug Resistance Mechanisms in Bacteria Causing Sexually Transmitted Diseases and Associated with Vaginosis. Here, we review sexually transmitted diseases (STDs) caused by pathogenic bacteria and vaginal infections which result from an overgrowth of opportunistic bacterial microflora. First, we describe the STDs, the corresponding pathogens and the antimicrobials used for their treatment. In addition to the well-known diseases caused by single pathogens (i.e., syphilis, gonococcal infections, and chlamydiosis), we consider polymicrobial reproductive tract infections (especially those that are difficult to effectively clinically manage). Then, we summarize the biochemical mechanisms that lead to antimicrobial resistance and the most recent data on the emergence of drug resistance in STD pathogens and bacteria associated with vaginosis. A large amount of research performed in the last 10-15 years has shed light on the enormous diversity of mechanisms of resistance developed by bacteria. A detailed understanding of the mechanisms of antimicrobials action and the emergence of resistance is necessary to modify existing drugs and to develop new ones directed against new targets. | 2016 | 27242760 |
| 284 | 8 | 0.9899 | Expression of a transposable antibiotic resistance element in Saccharomyces. Some eukaryotic genes can be expressed in bacteria but there are few examples of the expression of prokaryotic genes in eukaryotes. Antibiotic G418 is a 2-deoxystreptamine antibiotic that is structurally related to gentamicin but has inhibitory activity against a much wider variety of pro- and eukaryotic organisms. In bacteria, resistance to G418 can be determined by several plasmid-encoded modifiying enzymes and, in view of the broad spectrum of activity of G418, we considered that this antibiotic might be useful as a selective agent for the introduction of these antibiotic resistance genes into a eukaryotic organism such as Saccharomyces cerevisiae. Additional impetus for these experiments came from the knowledge that certain of the G418-resistance determinants in bacteria are carried on transposable elements; a study of the properties of these elements in eukaryotes would be intriguing. | 1980 | 6253817 |
| 9123 | 9 | 0.9899 | Antibiotic resistance of bacteria in biofilms. Bacteria that adhere to implanted medical devices or damaged tissue can encase themselves in a hydrated matrix of polysaccharide and protein, and form a slimy layer known as a biofilm. Antibiotic resistance of bacteria in the biofilm mode of growth contributes to the chronicity of infections such as those associated with implanted medical devices. The mechanisms of resistance in biofilms are different from the now familiar plasmids, transposons, and mutations that confer innate resistance to individual bacterial cells. In biofilms, resistance seems to depend on multicellular strategies. We summarise the features of biofilm infections, review emerging mechanisms of resistance, and discuss potential therapies. | 2001 | 11463434 |
| 9931 | 10 | 0.9899 | New beta-lactamases in gram-negative bacteria: diversity and impact on the selection of antimicrobial therapy. Of the 340 discrete beta-lactamases that have been identified, the most important groups of enzymes that are continuing to proliferate include the plasmid-encoded cephalosporinases, the metallo-beta-lactamases, and the extended-spectrum beta-lactamases. Resistance to specific beta-lactam-containing antimicrobial agents frequently can be traced to a single beta-lactamase, but this task is becoming more difficult for the clinical microbiology laboratory. Other factors, such as multiple beta-lactamase production, transferable multidrug-resistance genes, alterations in outer-membrane porins, and possible antibiotic efflux, all may contribute to a resistance phenotype. Appreciation of these factors may help the physician make a more informed decision when choosing therapy to try to avoid selection of even more pathogenic strains. | 2001 | 11264037 |
| 285 | 11 | 0.9899 | Streptothricin resistance as a novel selectable marker for transgenic plant cells. Streptothricins are known as antimicrobial agents produced by Streptomyces spp. Bacterial resistance to streptothricin is mediated by specific enzymes exhibiting an acetyltransferase activity which renders the drug non-toxic for bacteria. The nucleotide sequence of several streptothricin resistance genes from bacteria have been described. Certain cells of eukaryotic parasites (such as Ustilago maydis or Leishmania spp.) are sensitive to streptothricin and the introduction of the bacterial resistance gene sat2 renders them resistant. We show that numerous species of plants are sensitive to low concentrations of streptothricin. Moreover, introduction of the bacterial resistance gene sat3 under the control of the 35S cauliflower mosaic virus promoter protects these cells from the toxic action of streptothricin. Therefore, sat3-mediated streptothricin resistance appears to be a promising selective marker for genetic manipulation of plant cells. | 2000 | 30754912 |
| 9782 | 12 | 0.9898 | Homodimeric Tobramycin Adjuvant Repurposes Novobiocin as an Effective Antibacterial Agent against Gram-Negative Bacteria. Low permeability across the outer membrane is a major reason why most antibiotics are ineffective against Gram-negative bacteria. Agents that permeabilize the outer membrane are typically toxic at their effective concentrations. Here, we report the development of a broad-spectrum homodimeric tobramycin adjuvant that is nontoxic and more potent than the gold standard permeabilizing agent, polymyxin B nonapeptide. In pilot studies, the adjuvant confers potent bactericidal activity on novobiocin against Gram-negative bacteria, including carbapenem-resistant and colistin-resistant strains bearing plasmid-borne mcr-1 genes. Resistance development to the combination was significantly reduced, relative to novobiocin alone, and there was no induction of cross-resistance to other antibiotics, including the gyrase-acting fluoroquinolones. Tobramycin homodimer may allow the use of lower doses of novobiocin, overcoming its twin problem of efficacy and toxicity. | 2019 | 31557020 |
| 9824 | 13 | 0.9898 | Transposons: the agents of antibiotic resistance in bacteria. Transposons are a group of mobile genetic elements that are defined as a DNA sequence. Transposons can jump into different places of the genome; for this reason, they are called jumping genes. However, some transposons are always kept at the insertion site in the genome. Most transposons are inactivated and as a result, cannot move. Transposons are divided into two main groups: retrotransposons (class І) and DNA transposons (class ІІ). Retrotransposons are often found in eukaryotes. DNA transposons can be found in both eukaryotes and prokaryotes. The bacterial transposons belong to the DNA transposons and the Tn family, which are usually the carrier of additional genes for antibiotic resistance. Transposons can transfer from a plasmid to other plasmids or from a DNA chromosome to plasmid and vice versa that cause the transmission of antibiotic resistance genes in bacteria. The treatment of bacterial infectious diseases is difficult because of existing antibiotic resistance that part of this antibiotic resistance is caused by transposons. Bacterial infectious diseases are responsible for the increasing rise in world mortality rate. In this review, transposons and their roles have been studied in bacterial antibiotic resistance, in detail. | 2018 | 30113080 |
| 393 | 14 | 0.9898 | Antibiotic marker modifications of lambda Red and FLP helper plasmids, pKD46 and pCP20, for inactivation of chromosomal genes using PCR products in multidrug-resistant strains. The Red recombinase system of bacteriophage Lambda has been used to inactivate chromosomal genes in bacteria using PCR products. In this study, we describe the replacement of the ampicillin resistance marker of helper plasmids pKD46 and pCP20 by a gentamicin resistance gene to disrupt chromosomal genes and then to eliminate FRT flanked resistance gene in multiple antibiotic-resistant Salmonella enterica strains. | 2008 | 18619499 |
| 9748 | 15 | 0.9898 | Resistance in antimicrobial photodynamic inactivation of bacteria. Antibiotics have increasingly lost their impact to kill bacteria efficiently during the last 10 years. The emergence and dissemination of superbugs with resistance to multiple antibiotic classes have occurred among Gram-positive and Gram-negative strains including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter strains. These six superbugs can "escape" more or less any single kind of antibiotic treatment. That means bacteria are very good at developing resistance against antibiotics in a short time. One new approach is called photodynamic antimicrobial chemotherapy (PACT) which already has demonstrated an efficient antimicrobial efficacy among multi-resistant bacteria. Until now it has been questionable if bacteria can develop resistance against PACT. This perspective summarises the current knowledge about the susceptibility of bacteria towards oxidative stress and sheds some light on possible strategies of the development of photodynamic inactivation of bacteria (PACT)-induced oxidative stress resistance by bacteria. | 2015 | 26098395 |
| 8910 | 16 | 0.9898 | Chemical communication of antibiotic resistance by a highly resistant subpopulation of bacterial cells. The overall antibiotic resistance of a bacterial population results from the combination of a wide range of susceptibilities displayed by subsets of bacterial cells. Bacterial heteroresistance to antibiotics has been documented for several opportunistic Gram-negative bacteria, but the mechanism of heteroresistance is unclear. We use Burkholderia cenocepacia as a model opportunistic bacterium to investigate the implications of heterogeneity in the response to the antimicrobial peptide polymyxin B (PmB) and also other bactericidal antibiotics. Here, we report that B. cenocepacia is heteroresistant to PmB. Population analysis profiling also identified B. cenocepacia subpopulations arising from a seemingly homogenous culture that are resistant to higher levels of polymyxin B than the rest of the cells in the culture, and can protect the more sensitive cells from killing, as well as sensitive bacteria from other species, such as Pseudomonas aeruginosa and Escherichia coli. Communication of resistance depended on upregulation of putrescine synthesis and YceI, a widely conserved low-molecular weight secreted protein. Deletion of genes for the synthesis of putrescine and YceI abrogate protection, while pharmacologic inhibition of putrescine synthesis reduced resistance to polymyxin B. Polyamines and YceI were also required for heteroresistance of B. cenocepacia to various bactericidal antibiotics. We propose that putrescine and YceI resemble "danger" infochemicals whose increased production by a bacterial subpopulation, becoming more resistant to bactericidal antibiotics, communicates higher level of resistance to more sensitive members of the population of the same or different species. | 2013 | 23844246 |
| 6174 | 17 | 0.9898 | Genetic Variability of the AcrAB-TolC Multidrug Efflux Pump Underlies SkQ1 Resistance in Gram-Negative Bacteria. SkQ1, a novel antibiotic targeting bacterial bioenergetics, is highly effective against both gram-positive and gram-negative bacteria. However, some gram-negative bacteria, such as Escherichia coli and Klebsiella pneumoniae, are highly resistant to it. In different gram-negative bacteria, this resistance is associated with the identity of their AcrB transporter protein sequence with the sequence of the AcrB protein from E. coli. SkQ1 is expelled from E. coli cells by the AcrAB-TolC multidrug efflux pump. In this study, we demonstrate that SkQ1 resistance in E. coli, in contrast to chloramphenicol resistance, does not depend on the presence of the multidrug efflux pump accessory protein AcrZ. | 2019 | 31993240 |
| 534 | 18 | 0.9897 | Plasmid shuttle vector with two insertionally inactivable markers for coryneform bacteria. A new shuttle vector pCEM500 replicating in Escherichia coli and in Brevibacterium flavum was constructed. It carries two antibiotic resistance determinants (Kmr/Gmr from plasmid pSa of Gram-negative bacteria and Smr/Spr from plasmid pCG4 of Corynebacterium glutamicum) which are efficiently expressed in both hosts and can be inactivated by insertion of DNA fragments into the unique restriction endonuclease sites located within them. This vector was found to be stably maintained in B. flavum and can be used for transfer of the cloned genes into this amino-acid-producing coryneform bacterium. | 1990 | 2148164 |
| 4427 | 19 | 0.9897 | Mechanisms of quinolone action and microbial response. Over the years, chromosomal mapping of the bacterial genome of Escherichia coli has demonstrated that many loci are associated with quinolone resistance, which is mainly a result of chromosomal mutation or alteration of the quantity or type of porins in the outer membrane of Gram-negative bacteria. There has been one report of a small and confined episode of plasmid-mediated resistance to fluoroquinolones, which did not appear to persist. With the increasingly widespread use of an expanding range of fluoroquinolone antibiotics, a range and mix in individual bacterial isolates of the different mechanisms of resistance to fluoroquinolones will undoubtedly be encountered amongst clinically significant bacteria. Currently, transferable resistance is extremely rare and most resistant bacteria arise from clonal expansion of mutated strains. However, it is conceivable that in the future, horizontal gene transfer may become a more important means of conferring resistance to fluoroquinolones. | 2003 | 12702701 |