# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 4414 | 0 | 1.0000 | Macrolide resistance mechanisms in Gram-positive cocci. Two principal mechanisms of resistance to macrolides have been identified in Gram-positive bacteria. Erythromycin-resistant methylase is encoded by erm genes. Resultant structural changes to rRNA prevent macrolide binding and allow synthesis of bacterial proteins to continue. Presence of the erm gene results in high-level resistance. Modification of the mechanism whereby antibiotics are eliminated from the bacteria also brings about resistance. Bacteria carrying the gene encoding macrolide efflux (i.e. the mefE gene) display relatively low-level resistance. Azithromycin, because of its ability to achieve concentrations at sites of infections, is capable of eradicating mefE-carrying strains. Other resistance mechanisms, involving stimulation of enzymatic degradation, appear not to be clinically significant. | 2001 | 11574191 |
| 4831 | 1 | 0.9999 | Mechanism of quinolone resistance in anaerobic bacteria. Several recently developed quinolones have excellent activity against a broad range of aerobic and anaerobic bacteria and are thus potential drugs for the treatment of serious anaerobic and mixed infections. Resistance to quinolones is increasing worldwide, but is still relatively infrequent among anaerobes. Two main mechanisms, alteration of target enzymes (gyrase and topoisomerase IV) caused by chromosomal mutations in encoding genes, or reduced intracellular accumulation due to increased efflux of the drug, are associated with quinolone resistance. These mechanisms have also been found in anaerobic species. High-level resistance to the newer broad-spectrum quinolones often requires stepwise mutations in target genes. The increasing emergence of resistance among anaerobes may be a consequence of previous widespread use of quinolones, which may have enriched first-step mutants in the intestinal tract. Quinolone resistance in the Bacteroides fragilis group strains is strongly correlated with amino acid substitutions at positions 82 and 86 in GyrA (equivalent to positions 83 and 87 of Escherichia coli). Several studies have indicated that B. fragilis group strains possess efflux pump systems that actively expel quinolones, leading to resistance. DNA gyrase seems also to be the primary target for quinolones in Clostridium difficile, since amino acid substitutions in GyrA and GyrB have been detected in resistant strains. To what extent other mechanisms, such as mutational events in other target genes or alterations in outer-membrane proteins, contribute to resistance among anaerobes needs to be further investigated. | 2003 | 12848726 |
| 4416 | 2 | 0.9999 | Tetracycline resistance determinants: mechanisms of action, regulation of expression, genetic mobility, and distribution. Tetracycline-resistant bacteria were first isolated in 1953 from Shigella dysenteriae, a bacterium which causes bacterial dysentery. Since then tetracycline-resistant bacterial have been found in increasing numbers of species and genera. This has resulted in reduced effectiveness of tetracycline therapy over time. Tetracycline resistance is normally due to the acquisition of new genes often associated with either a mobile plasmid or a transposon. These tetracycline resistance determinants are distinguishable both genetically and biochemically. Resistance is primarily due to either energy-dependent efflux of tetracycline or protection of the ribosomes from the action of tetracycline. Gram-negative tetracycline efflux proteins are linked to repressor proteins which in the absence of tetracycline block transcription of the repressor and structural efflux genes. In contrast, expression of the Gram-positive tetracycline efflux genes and some of the ribosomal protection genes appears to be regulated by attenuation of mRNA transcription. Specific tetracycline resistance genes have been identified in 32 Gram-negative and 22 Gram-positive genera. Tetracycline-resistant bacteria are found in pathogens, opportunistic and normal flora species. Tetracycline-resistant bacteria can be isolated from man, animals, food, and the environment. The nonpathogens in each of these ecosystems may play an important role as reservoirs for the antibiotic resistance genes. It is clear that if we are to reverse the trend toward increasingly antibiotic-resistant pathogenic bacteria we will need to change how antibiotics are used in both human and animal health and food production. | 1996 | 8916553 |
| 4420 | 3 | 0.9998 | New perspectives in tetracycline resistance. Until recently, tetracycline efflux was thought to be the only mechanism of tetracycline resistance. As studies of tetracycline resistance have shifted to bacteria outside the Enterobacteriaceae, two other mechanisms of resistance have been discovered. The first is ribosomal protection, a type of resistance which is found in mycoplasmas, Gram-positive and Gram-negative bacteria and may be the most common type of tetracycline resistance in nature. The second is tetracycline modification, which has been found only in two strains of an obligate anaerobe (Bacteroides). Recent studies have also turned up such anomalies as a tetracycline efflux pump which does not confer resistance to tetracycline and a gene near the replication origin of a tetracycline-sensitive Bacillus strain which confers resistance when it is amplified. | 1990 | 2181236 |
| 4415 | 4 | 0.9998 | Staphylococcal resistance to streptogramins and related antibiotics. Streptogramin and related antibiotics are mixtures of two compounds, A and B (e.g. Dalfopristin and Quinupristin), particularly against Gram-positive bacteria. Staphylococci resistant to these mixtures are always resistant to the A compounds but are not necessarily resistant to the B compounds. Resistance to A compounds and to the mixtures is conferred by acetyltransferases or ATP-binding proteins via unknown mechanisms. Several genes encoding each of the two categories of protein have been characterized and regularly detected on plasmids. Genes encoding lactonases, which inactivate B compounds, have been occasionally detected on these plasmids. Staphylococci which harbour plasmids conferring resistance to A compounds should not be treated with the mixtures even if they appear susceptible in vitro. Indeed, susceptibility to the mixtures of staphylococci carrying resistance to A compounds has often been attributed to partial loss of the plasmids conferring this resistance. When staphylococci are constitutively resistant to B compounds, the in vitro activities of the mixtures should be evaluated, because they are better correlated than MICs with their efficacy in therapy. | 1998 | 17092802 |
| 4471 | 5 | 0.9998 | Update on acquired tetracycline resistance genes. This mini-review summarizes the changes in the field of bacterial acquired tetracycline resistance (tet) and oxytetracycline (otr) genes identified since the last major review in 2001. Thirty-eight acquired tetracycline resistant (Tc(r)) genes are known of which nine are new and include five genes coding for energy-dependent efflux proteins, two genes coding for ribosomal protection proteins, and two genes coding for tetracycline inactivating enzymes. The number of inactivating enzymes has increased from one to three, suggesting that work needs to be done to determine the role these enzymes play in bacterial resistance to tetracycline. In the same time period, 66 new genera have been identified which carry one or more of the previously described 29 Tc(r) genes. Included in the new genera is, for the first time, an obligate intracellular pathogen suggesting that this sheltered group of bacteria is capable of DNA exchange with non-obligate intracellular bacteria. The number of genera carrying ribosomal protection genes increased dramatically with the tet(M) gene now identified in 42 genera as compared with 24 and the tet(W) gene found in 17 new genera as compared to two genera in the last major review. New conjugative transposons, carrying different ribosomal protection tet genes, have been identified and an increase in the number of antibiotic resistance genes linked to tet genes has been found. Whether these new elements may help to spread the tet genes they carry to a wider bacterial host range is discussed. | 2005 | 15837373 |
| 4417 | 6 | 0.9998 | Genetic mobility and distribution of tetracycline resistance determinants. Since 1953, tetracycline-resistant bacteria have been found increasingly in humans, animals, food and the environment. Tetracycline resistance is normally due to the acquisition of new genes and is primarily due to either energy-dependent efflux of tetracycline or protection of the ribosomes from its action. Gram-negative efflux genes are frequently associated with conjugative plasmids, whereas Gram-positive efflux genes are often found on small mobilizable plasmids or in the chromosome. The ribosomal protection genes are generally associated with conjugative transposons which have a preference for the chromosome. Recently, tetracycline resistance genes have been found in the genera Mycobacterium, Nocardia, Streptomyces and Treponema. The Tet M determinant codes for a ribosomal protection protein which can be found in Gram-positive, Gram-negative, cell-wall-free, aerobic, anaerobic, pathogenic, opportunistic and normal flora species. This promiscuous nature may be correlated with its location on a conjugative transposon and its ability to cross most biochemical and physical barriers found in bacteria. The Tet B efflux determinant is unlike other efflux gene products because it confers resistance to tetracycline, doxycycline and minocycline and has the widest host range of all Gram-negative efflux determinants. We have hypothesized that mobility and the environment of the bacteria may help influence the ultimate host range of specific tet genes. If we are to reverse the trend towards increasingly antibiotic-resistant pathogenic bacteria, we will need to change how antibiotics are used in both human and animal health as well as food production. | 1997 | 9189643 |
| 4830 | 7 | 0.9998 | Mechanisms of resistance to quinolones. The increased use of fluoroquinolones has led to increasing resistance to these antimicrobials, with rates of resistance that vary by both organism and geographic region. Resistance to fluoroquinolones typically arises as a result of alterations in the target enzymes (DNA gyrase and topoisomerase IV) and of changes in drug entry and efflux. Mutations are selected first in the more susceptible target: DNA gyrase, in gram-negative bacteria, or topoisomerase IV, in gram-positive bacteria. Additional mutations in the next most susceptible target, as well as in genes controlling drug accumulation, augment resistance further, so that the most-resistant isolates have mutations in several genes. Resistance to quinolones can also be mediated by plasmids that produce the Qnr protein, which protects the quinolone targets from inhibition. Qnr plasmids have been found in the United States, Europe, and East Asia. Although Qnr by itself produces only low-level resistance, its presence facilitates the selection of higher-level resistance mutations, thus contributing to the alarming increase in resistance to quinolones. | 2005 | 15942878 |
| 6247 | 8 | 0.9998 | Molecular basis and evolutionary cost of a novel macrolides/lincosamides resistance phenotype in Staphylococcus haemolyticus. Staphylococcus haemolyticus (S. haemolyticus) is a coagulase-negative Staphylococcus that has become one of the primary causes of nosocomial infection. After a long period of antibiotic use, S. haemolyticus has developed multiple resistance phenotypes for macrolides and lincosamides. Herein, we evaluated four S. haemolyticus clinical isolates, of which three had antibiotic resistance patterns reported previously. The fourth isolate was resistant to both erythromycin and clindamycin in the absence of erythromycin induction. This novel phenotype, known as constitutive macrolides-lincosamides-streptogramins resistance, has been reported in other bacteria but has not been previously reported in S. haemolyticus. Investigation of the isolate demonstrated a deletion in the methyltransferase gene ermC, upstream leader peptide. This deletion resulted in constitutive MLS resistance based on whole-genome sequencing and experimental verification. Continuous expression of ermC was shown to inhibit the growth of S. haemolyticus, which turned out to be the fitness cost with no MLS pressure. In summary, this study is the first to report constitutive MLS resistance in S. haemolyticus, which provides a better understanding of MLS resistance in clinical medicine. IMPORTANCE This study identified a novel phenotype of macrolides/lincosamides resistance in Staphylococcus haemolyticus which improved a better guidance for clinical treatment. It also clarified the mechanistic basis for this form of antibiotic resistance that supplemented the drug resistance mechanism of Staphylococcus. In addition, this study elaborated on a possibility that continuous expression of some resistance genes was shown to inhibit the growth of bacteria themselves, which turned out to be the fitness cost in the absence of antibiotic pressure. | 2023 | 37724875 |
| 4419 | 9 | 0.9998 | Epidemiology of tetracycline-resistance determinants. Resistance to tetracycline is generally due either to energy-dependent efflux of tetracycline or to protection of the bacterial ribosomes from the action of tetracycline. The genes that encode this resistance are normally acquired via transferable plasmids and/or transposons. Tet determinants have been found in a wide range of Gram-positive and Gram-negative bacteria and have reduced the effectiveness of therapy with tetracycline. | 1994 | 7850200 |
| 4418 | 10 | 0.9998 | Bacterial resistance to tetracycline: mechanisms, transfer, and clinical significance. Tetracycline has been a widely used antibiotic because of its low toxicity and broad spectrum of activity. However, its clinical usefulness has been declining because of the appearance of an increasing number of tetracycline-resistant isolates of clinically important bacteria. Two types of resistance mechanisms predominate: tetracycline efflux and ribosomal protection. A third mechanism of resistance, tetracycline modification, has been identified, but its clinical relevance is still unclear. For some tetracycline resistance genes, expression is regulated. In efflux genes found in gram-negative enteric bacteria, regulation is via a repressor that interacts with tetracycline. Gram-positive efflux genes appear to be regulated by an attenuation mechanism. Recently it was reported that at least one of the ribosome protection genes is regulated by attenuation. Tetracycline resistance genes are often found on transmissible elements. Efflux resistance genes are generally found on plasmids, whereas genes involved in ribosome protection have been found on both plasmids and self-transmissible chromosomal elements (conjugative transposons). One class of conjugative transposon, originally found in streptococci, can transfer itself from streptococci to a variety of recipients, including other gram-positive bacteria, gram-negative bacteria, and mycoplasmas. Another class of conjugative transposons has been found in the Bacteroides group. An unusual feature of the Bacteroides elements is that their transfer is enhanced by preexposure to tetracycline. Thus, tetracycline has the double effect of selecting for recipients that acquire a resistance gene and stimulating transfer of the gene. | 1992 | 1423217 |
| 4829 | 11 | 0.9998 | Diversity of the mechanisms of resistance to beta-lactam antibiotics. The sensitivity of a bacterium to beta-lactam antibiotics depends upon the interplay between 3 independent factors: the sensitivity of the essential penicillin-binding enzyme(s), the quantity and properties of the beta-lactamase(s) and the diffusion barrier that the outer-membrane of Gram-negative bacteria can represent. Those three factors can be modified by mutations or by the horizontal transfer of genes or portions of genes. | 1991 | 1961980 |
| 6275 | 12 | 0.9998 | 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 |
| 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 |
| 4483 | 14 | 0.9998 | Ribosomal Resistance: Emerging Problems and Potential Solutions. Many systemic antibiotics use ribosomal inhibition to suppress the replication of bacteria. Current research suggests that resistance to macrolide, lincosamide, and streptogramin B (MLS(B)) antibiotics is emerging among clinical isolates of Streptococcus pyogenes and Streptococcus pneumoniae. Erythromycin methylases, encoded by erm genes, modify an essential adenine residue in 23S rRNA and confer cross-resistance to MLS(B) antibiotics. More recently, macrolide efflux (mef) genes were identified in isolates of S. pyogenes and S. pneumoniae that show resistance to 14- and 15-membered macrolides (M phenotype). Resistance to MLSB has been associated with the increased use of erythromycin, and the recent emergence of the M phenotype has coincided with the marketing of newer macrolides. However, despite increasing macrolide resistance among clinical isolates of S. pneumoniae, convincing data on treatment failures directly attributable to MLS(B) or M phenotypes are limited. Possible solutions to emerging MLS(B) and M phenotype resistance include the introduction of alternative antibiotics, the more prudent use of antibiotics, combination therapy, molecular diagnostics, enhanced understanding of pharmacodynamic variables, and redefined resistance breakpoints. | 1999 | 11095824 |
| 6333 | 15 | 0.9998 | Outer Membrane Proteins form Specific Patterns in Antibiotic-Resistant Edwardsiella tarda. Outer membrane proteins of Gram-negative bacteria play key roles in antibiotic resistance. However, it is unknown whether outer membrane proteins that respond to antibiotics behave in a specific manner. The present study specifically investigated the differentially expressed outer membrane proteins of an antibiotic-resistant bacterium, Edwardsiella tarda, a Gram-negative pathogen that can lead to unnecessary mass medication of antimicrobials and consequently resistance development in aquaculture and a spectrum of intestinal and extraintestinal diseases in humans. The comparison of a clinically isolated strain to the laboratory derived kanamycin-, tetracycline-, or chloramphenicol-resistant strains identified their respective outer membrane proteins expression patterns, which are distinct to each other. Similarly, the same approach was utilized to profile the patterns in double antibiotic-resistant bacteria. Surprisingly, one pattern is always dominant over the other as to these three antibiotics; the pattern of chloramphenicol is over tetracycline, which is over kanamycin. This type of pattern was also confirmed in clinically relevant multidrug-resistant bacteria. In addition, the presence of plasmid encoding antibiotic-resistant genes also alters the outer membrane protein profile in a similar manner. Our results demonstrate that bacteria adapt the antibiotic stress through the regulation of outer membrane proteins expression. And more importantly, different outer membrane protein profiles were required to cope with different antibiotics. This type of specific pattern provides the rationale for the development of novel strategy to design outer membrane protein arrays to identify diverse multidrug resistance profiles as biomarkers for clinical medication. | 2017 | 28210241 |
| 4429 | 16 | 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 |
| 4488 | 17 | 0.9998 | The cfr and cfr-like multiple resistance genes. The Cfr methyl transferase causes an RNA methylation of the bacterial ribosomes impeding reduced or abolished binding of many antibiotics acting at the peptidyl transferase center. It provides multi-resistance to eight classes of antibiotics, most of which are in clinical and veterinary use. The cfr gene is found in various bacteria in many geographical locations and placed on plasmids or associated with transposons. Cfr-related genes providing similar resistance have been identified in Bacillales, and now also in the pathogens Clostridium difficile and Enterococcus faecium. In addition, the presence of the cfr gene has been detected in harbours and food markets. | 2018 | 29378339 |
| 4381 | 18 | 0.9998 | Specific Gene Loci of Clinical Pseudomonas putida Isolates. Pseudomonas putida are ubiquitous inhabitants of soils and clinical isolates of this species have been seldom described. Clinical isolates show significant variability in their ability to cause damage to hosts because some of them are able to modulate the host's immune response. In the current study, comparisons between the genomes of different clinical and environmental strains of P. putida were done to identify genetic clusters shared by clinical isolates that are not present in environmental isolates. We show that in clinical strains specific genes are mostly present on transposons, and that this set of genes exhibit high identity with genes found in pathogens and opportunistic pathogens. The set of genes prevalent in P. putida clinical isolates, and absent in environmental isolates, are related with survival under oxidative stress conditions, resistance against biocides, amino acid metabolism and toxin/antitoxin (TA) systems. This set of functions have influence in colonization and survival within human tissues, since they avoid host immune response or enhance stress resistance. An in depth bioinformatic analysis was also carried out to identify genetic clusters that are exclusive to each of the clinical isolates and that correlate with phenotypical differences between them, a secretion system type III-like was found in one of these clinical strains, a determinant of pathogenicity in Gram-negative bacteria. | 2016 | 26820467 |
| 4424 | 19 | 0.9998 | Gene transfer, gentamicin resistance and enterococci. Enterococci are versatile pathogens by virtue of their ability to exhibit low-level intrinsic resistance to clinically useful antibiotics and their tolerance to adverse environmental conditions. In the last 20 years these pathogens have become progressively more difficult to treat because of their aptitude for acquiring antibiotic-resistance genes. Of increasing concern is the rapid dissemination of the AAC6'-APH2" bi-functional aminoglycoside modifying enzyme. This enzyme confers high-level resistance to gentamicin and all other related aminoglycosides with the exception of streptomycin. The gene conferring this phenotype has been associated with both narrow and broad host range plasmids, and has recently been found on conjugative transposons. The nature of these conjugative elements raises the possibility of the resistance gene spreading to other pathogenic bacteria. | 1997 | 9261754 |