# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 6176 | 0 | 0.9971 | Involvement of GcvB small RNA in intrinsic resistance to multiple aminoglycoside antibiotics in Escherichia coli. Deleting the gene for small RNA GcvB in Escherichia coli was found to increase the sensitivity to several aminoglycoside antibiotics, such as neomycin, streptomycin, kanamycin, kasugamycin and spectinomycin, at low concentrations. GcvB, conserved in gram-negative enteric bacteria, is known to negatively control the expression of many genes for amino acid incorporation systems, especially the periplasmic ABC-transporter proteins. Deletions of several amino acid transporter genes in ΔgcvB cells decreased the antibiotic sensitivity to the wild-type level, suggesting that those genes are involved in uptake of aminoglycosides into the cell. Since GcvB is constitutively synthesized in growing cells, repressing synthesis of amino acid transporters, it contributes to the intrinsic resistance to several aminoglycoside antibiotics. | 2021 | 33169170 |
| 321 | 1 | 0.9970 | Mutability in Pseudomonas viridiflava as a programmed balance between antibiotic resistance and pathogenicity. Mutable bacterial cells are defective in their DNA repair system and often have a phenotype different from that of their wild-type counterparts. In human bacterial pathogens, the mutable and hypermutable phenotypes are often associated with general antibiotic resistance. Here, we quantified the occurrence of mutable cells in Pseudomonas viridiflava, a phytopathogenic bacterium in the P. syringae complex with a broad host range and capacity to live as a saprophyte. Two phenotypic variants (transparent and mucoid) were produced by this bacterium. The transparent variant had a mutator phenotype, showed general antibiotic resistance and could not induce disease on the plant species tested (bean). In contrast, the mucoid variant did not display mutability or resistance to antibiotics and was capable of inducing disease on bean. Both the transparent and mucoid variants were less fit when grown in vitro, whereas, in planta, both of the variants and wild-types attained similar population densities. Given the importance of the methyl-directed mismatch repair system (MMR) in the occurrence of mutable and hypermutable cells in human bacterial pathogens, we investigated whether mutations in mut genes were associated with mutator transparent cells in P. viridiflava. Our results showed no mutations in MMR genes in any of the P. viridiflava cells tested. Here, we report that a high mutation rate and antibiotic resistance are inversely correlated with pathogenicity in P. viridiflava, but are not associated with mutations in MMR. In addition, P. viridiflava variants differ from variants produced by other phytopathogenic bacteria in the absence of reversion to the wild-type phenotype. | 2015 | 25649542 |
| 4485 | 2 | 0.9969 | Distribution of macrolide, lincosamide, streptogramin, ketolide and oxazolidinone (MLSKO) resistance genes in Gram-negative bacteria. A number of different mechanisms of macrolide resistance have been described in Gram-negative bacteria. These include 16 acquired genes (esterases, phosphorylases, rRNA methylases, and effluxes) and include those thought to be unique to Gram-negative bacteria (both esterases and two of the phosphorylases) and those shared with Gram-positive bacteria (one phosphorylase) and those primarily of Gram-positive origin (rRNA methylases and efflux genes). In addition, mutations, which modify the 23S rRNA, ribosomal proteins L4 and/or L22, and/or changes in expression of innate efflux systems which occur by missense, deletion and/or insertion events have been described in five Gram-negative groups, while an innate transferase conferring resistance to streptogramin A has been identified in a sixth genus. However, the amount of information on both acquisition and mutations leading to macrolide, lincosamides, streptogramins, ketolides and oxazolidinones (MLSKO) resistance is limited. As a consequence this review likely underestimates the true distribution of acquired genes and mutations in Gram-negative bacteria. As use of these drugs increases, it is likely that interaction between members of the MLSKO antibiotic family and Gram-negative bacteria will continue to change resistance to these antibiotics; by mutations of existing genes as well as by acquisition and perhaps mutations of acquired resistant genes in these organisms and more work needs to be done to get a clearer picture of what is in the Gram-negative population now, such that changes can be monitored. | 2004 | 15379732 |
| 206 | 3 | 0.9969 | Review of preclinical studies with ofloxacin. Most Enterobacteriaceae, enteropathogens, and fastidious gram-negative bacteria are highly susceptible to ofloxacin, a new tricyclic fluoroquinolone. Aerobic gram-negative bacilli and gram-positive bacteria are generally not as susceptible to ofloxacin. Obligate anaerobes are generally resistant to ofloxacin, while many mycobacteria, chlamydiae, legionellae, and mycoplasmas are susceptible. Ofloxacin is generally less active than ciprofloxacin against gram-negative bacteria, is similarly active against gram-positive bacteria, mycobacteria, legionellae, and mycoplasmas, and is more active against chlamydiae. However, numerous animal studies have shown these two fluoroquinolones to be similar. Ofloxacin inhibits DNA synthesis, is rapidly bactericidal, and is 1,000-2,400 times more potent against prokaryotic gyrase than against eukaryotic gyrase. The bactericidal effect of ofloxacin is not completely neutralized by inhibitors of protein or RNA synthesis. Resistance to ofloxacin arises from mutations within chromosomal genes involved with DNA gyrase and drug permeation. Selection of resistant mutants by ofloxacin is not as frequent as that seen with nalidixic acid. However, due to the cross-resistance between ofloxacin and other fluoroquinolones, all of these drugs should be used judiciously to preserve their clinical utility. | 1992 | 1554842 |
| 4420 | 4 | 0.9969 | 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 |
| 273 | 5 | 0.9968 | Coevolution of antibiotic production and counter-resistance in soil bacteria. We present evidence for the coexistence and coevolution of antibiotic resistance and biosynthesis genes in soil bacteria. The distribution of the streptomycin (strA) and viomycin (vph) resistance genes was examined in Streptomyces isolates. strA and vph were found either within a biosynthetic gene cluster or independently. Streptomyces griseus strains possessing the streptomycin cluster formed part of a clonal complex. All S. griseus strains possessing solely strA belonged to two clades; both were closely related to the streptomycin producers. Other more distantly related S. griseus strains did not contain strA. S. griseus strains with only vph also formed two clades, but they were more distantly related to the producers and to one another. The expression of the strA gene was constitutive in a resistance-only strain whereas streptomycin producers showed peak strA expression in late log phase that correlates with the switch on of streptomycin biosynthesis. While there is evidence that antibiotics have diverse roles in nature, our data clearly support the coevolution of resistance in the presence of antibiotic biosynthetic capability within closely related soil dwelling bacteria. This reinforces the view that, for some antibiotics at least, the primary role is one of antibiosis during competition in soil for resources. | 2010 | 20067498 |
| 8910 | 6 | 0.9968 | 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 |
| 695 | 7 | 0.9968 | Bacterial discrimination by dictyostelid amoebae reveals the complexity of ancient interspecies interactions. BACKGROUND: Amoebae and bacteria interact within predator-prey and host-pathogen relationships, but the general response of amoeba to bacteria is not well understood. The amoeba Dictyostelium discoideum feeds on, and is colonized by, diverse bacterial species, including Gram-positive [Gram(+)] and Gram-negative [Gram(-)] bacteria, two major groups of bacteria that differ in structure and macromolecular composition. RESULTS: Transcriptional profiling of D. discoideum revealed sets of genes whose expression is enriched in amoebae interacting with different species of bacteria, including sets that appear specific to amoebae interacting with Gram(+) or with Gram(-) bacteria. In a genetic screen utilizing the growth of mutant amoebae on a variety of bacteria as a phenotypic readout, we identified amoebal genes that are only required for growth on Gram(+) bacteria, including one that encodes the cell-surface protein gp130, as well as several genes that are only required for growth on Gram(-) bacteria, including one that encodes a putative lysozyme, AlyL. These genes are required for parts of the transcriptional response of wild-type amoebae, and this allowed their classification into potential response pathways. CONCLUSIONS: We have defined genes that are critical for amoebal survival during feeding on Gram(+), or Gram(-), bacteria that we propose form part of a regulatory network that allows D. discoideum to elicit specific cellular responses to different species of bacteria in order to optimize survival. | 2013 | 23664307 |
| 4430 | 8 | 0.9968 | βLactam Resistance Mediated by Changes in Penicillin-Binding Proteins. The widespread use, or perhaps overuse, of penicillin during the past 50 yr has driven the evolution of resistance to penicilling in numerous different species of bacteria.Typically, resistance has arisen as a result of the acquisition of β-lactamases that inactivate the antibiotic (see Chapter 25 . Alternatively, in some Gram-negative bacteria, resistance may have arisen by a reduction in the ability of the antibiotic to access its target. However, in a number of clinically important Gram-negative and Gram-positive bacteria, resistance has arisen by alteration of the targets for penicillin and other β-lactam antibiotics, namely, the penicillin-binding proteins (PBPs). | 1998 | 21390765 |
| 270 | 9 | 0.9967 | Three genes controlling streptomycin susceptibility in Agrobacterium fabrum. Streptomycin (Sm) is a commonly used antibiotic for its efficacy against diverse bacteria. The plant pathogen Agrobacterium fabrum is a model for studying pathogenesis and interkingdom gene transfer. Streptomycin-resistant variants of A. fabrum are commonly employed in genetic analyses, yet mechanisms of resistance and susceptibility to streptomycin in this organism have not previously been investigated. We observe that resistance to a high concentration of streptomycin arises at high frequency in A. fabrum, and we attribute this trait to the presence of a chromosomal gene (strB) encoding a putative aminoglycoside phosphotransferase. We show how strB, along with rpsL (encoding ribosomal protein S12) and rsmG (encoding a 16S rRNA methyltransferase), modulates streptomycin sensitivity in A. fabrum. IMPORTANCE The plant pathogen Agrobacterium fabrum is a widely used model bacterium for studying biofilms, bacterial motility, pathogenesis, and gene transfer from bacteria to plants. Streptomycin (Sm) is an aminoglycoside antibiotic known for its broad efficacy against gram-negative bacteria. A. fabrum exhibits endogenous resistance to somewhat high levels of streptomycin, but the mechanism underlying this resistance has not been elucidated. Here, we demonstrate that this resistance is caused by a chromosomally encoded streptomycin-inactivating enzyme, StrB, that has not been previously characterized in A. fabrum. Furthermore, we show how the genes rsmG, rpsL, and strB jointly modulate streptomycin susceptibility in A. fabrum. | 2023 | 37695858 |
| 9408 | 10 | 0.9967 | Genomic evidence for antibiotic resistance genes of actinomycetes as origins of antibiotic resistance genes in pathogenic bacteria simply because actinomycetes are more ancestral than pathogenic bacteria. Although in silico analysis have suggested that the antibiotic resistance genes in actinomycetes appear to be the origins of some antibiotic resistance genes, we have shown that recent horizontal transfer of antibiotic resistance genes from actinomycetes to other medically important bacteria have not taken place. Although it has been speculated in Benveniste and Davies' attractive hypothesis that antibiotic resistance genes of actinomycetes are origins of antibiotic resistance genes in pathogenic bacteria because the actinomycetes require mechanisms such as metabolic enzymes (encoded by the antibiotic resistance genes) to degrade the antibiotics they produce or to transport the antibiotics outside the bacterial cells, this hypothesis has never been proven. Both the phylogenetic tree constructed using 16S rRNA gene sequences and that constructed using concatenated amino acid sequences of 15 housekeeping genes extracted from 90 bacterial genomes showed that the actinomycetes is more ancestral to most other bacteria, including the pathogenic Gram-negative bacteria, Gram-positive bacteria, and Chlamydia species. Furthermore, the tetracycline resistance gene of Bifidobacterium longum is more ancestral to those of other pathogenic bacteria and the actinomycetes, which is in line with the ancestral position of B. longum. These suggest that the evolution of antibiotic resistance genes of antibiotic-producing bacteria in general parallels the evolution of the corresponding bacteria. The ancestral position of the antibiotic resistance genes in actinomycetes is probably unrelated to the fact that they produce antibiotics, but simply because actinomycetes are more ancestral than pathogenic bacteria. | 2006 | 16824692 |
| 4415 | 11 | 0.9967 | 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 |
| 6324 | 12 | 0.9967 | Genetic and biochemical basis of tetracycline resistance. Properties of several, well characterized, tetracycline resistance determinants were compared. The determinants in Tn1721 and Tn10 (both from Gram-negative bacteria) each contain two genes; one encodes a repressor that regulates both its own transcription and that of a membrane protein that confers resistance by promoting efflux of the drug. Determinants from Gram-positive bacteria also encode efflux proteins, but expression of resistance is probably regulated by translational attenuation. The likely tetracycline binding site (a common dipeptide) in each efflux protein was predicted. The presence of the common binding site is consistent with the ability of an efflux protein originating in Bacillus species to be expressed in Escherichia coli. | 1986 | 3542941 |
| 554 | 13 | 0.9967 | VanZ Reduces the Binding of Lipoglycopeptide Antibiotics to Staphylococcus aureus and Streptococcus pneumoniae Cells. vanZ, a member of the VanA glycopeptide resistance gene cluster, confers resistance to lipoglycopeptide antibiotics independent of cell wall precursor modification by the vanHAX genes. Orthologs of vanZ are present in the genomes of many clinically relevant bacteria, including Enterococcus faecium and Streptococcus pneumoniae; however, vanZ genes are absent in Staphylococcus aureus. Here, we show that the expression of enterococcal vanZ paralogs in S. aureus increases the minimal inhibitory concentrations of lipoglycopeptide antibiotics teicoplanin, dalbavancin, oritavancin and new teicoplanin pseudoaglycone derivatives. The reduction in the binding of fluorescently labeled teicoplanin to the cells suggests the mechanism of VanZ-mediated resistance. In addition, using a genomic vanZ gene knockout mutant of S. pneumoniae, we have shown that the ability of VanZ proteins to compromise the activity of lipoglycopeptide antibiotics by reducing their binding is a more general feature of VanZ-superfamily proteins. | 2020 | 32318043 |
| 4439 | 14 | 0.9967 | beta-lactam resistance in Streptococcus pneumoniae: penicillin-binding proteins and non-penicillin-binding proteins. The beta-lactams are by far the most widely used and efficacious of all antibiotics. Over the past few decades, however, widespread resistance has evolved among most common pathogens. Streptococcus pneumoniae has become a paradigm for understanding the evolution of resistance mechanisms, the simplest of which, by far, is the production of beta-lactamases. As these enzymes are frequently plasmid encoded, resistance can readily be transmitted between bacteria. Despite the fact that pneumococci are naturally transformable organisms, no beta-lactamase-producing strain has yet been described. A much more complex resistance mechanism has evolved in S. pneumoniae that is mediated by a sophisticated restructuring of the targets of the beta-lactams, the penicillin-binding proteins (PBPs); however, this may not be the whole story. Recently, a third level of resistance mechanisms has been identified in laboratory mutants, wherein non-PBP genes are mutated and resistance development is accompanied by deficiency in genetic transformation. Two such non-PBP genes have been described: a putative glycosyltransferase, CpoA, and a histidine protein kinase, CiaH. We propose that these non-PBP genes are involved in the biosynthesis of cell wall components at a step prior to the biosynthetic functions of PBPs, and that the mutations selected during beta-lactam treatment counteract the effects caused by the inhibition of penicillin-binding proteins. | 1999 | 10447877 |
| 8379 | 15 | 0.9967 | Comparative study of the marR genes within the family Enterobacteriaceae. marR genes are members of an ancient family originally identified in Escherichia coli. This family is widely distributed in archaea and bacteria. Homologues of this family have a conserved winged helix fold. MarR proteins are involved in non-specific resistance systems conferring resistance to multiple antibiotics. Extensive studies have shown the importance of MarR proteins in physiology and pathogenicity in Enterobacteria, but little is known about their origin or evolution. In this study, all the marR genes in 43 enterobacterial genomes representing 14 genera were identified, and the phylogenetic relationships and genetic parameters were analyzed. Several major findings were made. Three conserved marR genes originated earlier than Enterobacteriaceae and a geneloss event was found to have taken place in Yersinia pestis Antiqua. Three functional genes, rovA, hor, and slyA, were found to be clear orthologs among Enterobacteriaceae. The copy number of marR genes in Enterobacteriaceae was found to vary from 2 to 11. These marR genes exhibited a faster rate of nucleotide substitution than housekeeping genes did. Specifically, the regions of marR domain were found to be subject to strong purifying selection. The phylogenetic relationship and genetic parameter analyses were consistent with conservation and specificity of marR genes. These dual characters helped MarR to maintain a conserved binding motif and variable C-terminus, which are important to adaptive responses to a number of external stimuli in Enterobacteriaceae. | 2014 | 24723108 |
| 395 | 16 | 0.9967 | 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 |
| 9826 | 17 | 0.9967 | Horizontal genetic exchange, evolution, and spread of antibiotic resistance in bacteria. Some transformable bacteria have acquired target-mediated antibiotic resistance by horizontal genetic exchange of fragments of chromosomal genes. The resistant strains express variants of the antibiotic target that are metabolically active but exhibit a lowered affinity for the antibiotic. The alleles encoding these resistant proteins are mosaics comprising DNA derived from the host and other bacteria, often members of a different species. Examples include penicillin-resistant penicillin-binding proteins (PBPs) in Streptococcus pneumoniae and the pathogenic Neisseria species and sulfonamide-resistant dihydropterate synthase in Neisseria meningitidis. Distinct mosaic alleles encoding antibiotic resistance have arisen on multiple occasions, indicating the mobility of chromosomal genes in these species. Mosaic genes can arise at any chromosomal locus, and S. pneumoniae organisms with high-level penicillin resistance have acquired mosaic PBP genes at three bacterial bpb loci. Furthermore, horizontal genetic exchange permits movement of alleles among bacterial lineages, increasing the opportunities for the spread of antibiotic resistance. | 1998 | 9710667 |
| 9291 | 18 | 0.9967 | Highlights of Streptomyces genetics. Sixty years ago, the actinomycetes, which include members of the genus Streptomyces, with their bacterial cellular dimensions but a mycelial growth habit like fungi, were generally regarded as a possible intermediate group, and virtually nothing was known about their genetics. We now know that they are bacteria, but with many original features. Their genome is linear with a unique mode of replication, not circular like those of nearly all other bacteria. They transfer their chromosome from donor to recipient by a conjugation mechanism, but this is radically different from the E. coli paradigm. They have twice as many genes as a typical rod-shaped bacterium like Escherichia coli or Bacillus subtilis, and the genome typically carries 20 or more gene clusters encoding the biosynthesis of antibiotics and other specialised metabolites, only a small proportion of which are expressed under typical laboratory screening conditions. This means that there is a vast number of potentially valuable compounds to be discovered when these 'sleeping' genes are activated. Streptomyces genetics has revolutionised natural product chemistry by facilitating the analysis of novel biosynthetic steps and has led to the ability to engineer novel biosynthetic pathways and hence 'unnatural natural products', with potential to generate lead compounds for use in the struggle to combat the rise of antimicrobial resistance. | 2019 | 31189905 |
| 296 | 19 | 0.9967 | An indigenous posttranscriptional modification in the ribosomal peptidyl transferase center confers resistance to an array of protein synthesis inhibitors. A number of nucleotide residues in ribosomal RNA (rRNA) undergo specific posttranscriptional modifications. The roles of most modifications are unclear, but their clustering in functionally important regions of rRNA suggests that they might either directly affect the activity of the ribosome or modulate its interactions with ligands. Of the 25 modified nucleotides in Escherichia coli 23S rRNA, 14 are located in the peptidyl transferase center, the main antibiotic target in the large ribosomal subunit. Since nucleotide modifications have been closely associated with both antibiotic sensitivity and antibiotic resistance, loss of some of these posttranscriptional modifications may affect the susceptibility of bacteria to antibiotics. We investigated the antibiotic sensitivity of E. coli cells in which the genes of 8 rRNA-modifying enzymes targeting the peptidyl transferase center were individually inactivated. The lack of pseudouridine at position 2504 of 23S rRNA was found to significantly increase the susceptibility of bacteria to peptidyl transferase inhibitors. Therefore, this indigenous posttranscriptional modification may have evolved as an intrinsic resistance mechanism protecting bacteria against natural antibiotics. | 2008 | 18554609 |