# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 333 | 0 | 0.9897 | Mutants of Escherichia coli altered in both genes coding for the elongation factor Tu. Genetic analysis of a mutant of Escherichia coli resistant to the antibiotic mocimycin is presented. This resistance is due to alterations in both tuf genes coding for the elongation factor Tu. Mocimycin resistance is recessive. Bacteria carryong only one tuf gene from the resistant mutant are still mocimycin sensitive. If the mutant gene is the tufA gene, the seisitive cells can be made resistant through inactivation of the tufB gene by insertion of the bacteriophage milliunits genome. Conditional mocimycin-resistant mutants ban also be isolated when the tufB gene is altered by an amber or a temperature-sensitive mutation. When only the tufB allele from the original mocimycin-resistant mutant is present, inactivation of the wild-type tufA gene fails to give viable mocimycin-resistant progeny. We conclude that the tufA mutant allele codes for a functional mocimycin-resistant EF-Tu, whereas the mutant tufB gene does not code for a functional product. | 1978 | 360222 |
| 654 | 1 | 0.9894 | Conjugation inhibitors compete with palmitic acid for binding to the conjugative traffic ATPase TrwD, providing a mechanism to inhibit bacterial conjugation. Bacterial conjugation is a key mechanism by which bacteria acquire antibiotic resistance. Therefore, conjugation inhibitors (COINs) are promising compounds in the fight against the spread of antibiotic resistance genes among bacteria. Unsaturated fatty acids (uFAs) and alkynoic fatty acid derivatives, such as 2-hexadecanoic acid (2-HDA), have been reported previously as being effective COINs. The traffic ATPase TrwD, a VirB11 homolog in plasmid R388, is the molecular target of these compounds, which likely affect binding of TrwD to bacterial membranes. In this work, we demonstrate that COINs are abundantly incorporated into Escherichia coli membranes, replacing palmitic acid as the major component of the membrane. We also show that TrwD binds palmitic acid, thus facilitating its interaction with the membrane. Our findings also suggest that COINs bind TrwD at a site that is otherwise occupied by palmitic acid. Accordingly, molecular docking predictions with palmitic acid indicated that it shares the same binding site as uFAs and 2-HDA, although it differs in the contacts involved in this interaction. We also identified 2-bromopalmitic acid, a palmitate analog that inhibits many membrane-associated enzymes, as a compound that effectively reduces TrwD ATPase activity and bacterial conjugation. Moreover, we demonstrate that 2-bromopalmitic and palmitic acids both compete for the same binding site in TrwD. Altogether, these detailed findings open up a new avenue in the search for effective synthetic inhibitors of bacterial conjugation, which may be pivotal for combating multidrug-resistant bacteria. | 2018 | 30201608 |
| 8424 | 2 | 0.9888 | Postseptational chromosome partitioning in bacteria. Mutations in the spoIIIE gene prevent proper partitioning of one chromosome into the developing prespore during sporulation but have no overt effect on partitioning in vegetatively dividing cells. However, the expression of spoIIIE in vegetative cells and the occurrence of genes closely related to spoIIIE in a range of nonsporulating eubacteria suggested a more general function for the protein. Here we show that SpoIIIE protein is needed for optimal chromosome partitioning in vegetative cells of Bacillus subtilis when the normal tight coordination between septation and nucleoid partitioning is perturbed or when septum positioning is altered. A functional SpoIIIE protein allows cells to recover from a state in which their chromosome has been trapped by a closing septum. By analogy to its function during sporulation, we suggest that SpoIIIE facilitates partitioning by actively translocating the chromosome out of the septum. In addition to enhancing the fidelity of nucleoid partitioning, SpoIIIE also seems to be required for maximal resistance to antibiotics that interfere with DNA metabolism. The results have important implications for our understanding of the functions of genes involved in the primary partitioning machinery in bacteria and of how septum placement is controlled. | 1995 | 7567988 |
| 724 | 3 | 0.9887 | Xanthomonas citri T6SS mediates resistance to Dictyostelium predation and is regulated by an ECF σ factor and cognate Ser/Thr kinase. Plant-associated bacteria of the genus Xanthomonas cause disease in a wide range of economically important crops. However, their ability to persist in the environment is still poorly understood. Predation by amoebas represents a major selective pressure to bacterial populations in the environment. In this study, we show that the X. citri type 6 secretion system (T6SS) promotes resistance to predation by the soil amoeba Dictyostelium discoideum. We found that an extracytoplasmic function (ECF) sigma factor (EcfK) is required for induction of T6SS genes during interaction with Dictyostelium. EcfK homologues are found in several environmental bacteria in association with a gene encoding a eukaryotic-like Ser/Thr kinase (pknS). Deletion of pknS causes sensitivity to amoeba predation and abolishes induction of T6SS genes. Phosphomimetic mutagenesis of EcfK identified a threonine residue (T51) that renders EcfK constitutively active in standard culture conditions. Moreover, susceptibility of ΔpknS to Dictyostelium predation can be overcome by expression of the constitutively active version EcfK(T51E) from a multicopy plasmid. Together, these results describe a new regulatory cascade in which PknS functions through activation of EcfK to promote T6SS expression. Our work reveals an important aspect of Xanthomonas physiology that affects its ability to persist in the environment. | 2018 | 29488354 |
| 347 | 4 | 0.9886 | A novel plasmid gene involved in bacteriophage PRD1 infection and conjugative host-range. PRD1 infects bacteria carrying IncN plasmids by binding to their conjugative pili. Mutations in a plasmid locus kikA close to the pilus region result in PRD1 resistance and reduced conjugation proficiency to Klebsiella but not to Escherichia coli. One of the two genes of kikA is sufficient to restore both normal phenotypes. PRD1 binds to cells carrying the mutant plasmid but fails to inject its genome. | 1996 | 8812786 |
| 8423 | 5 | 0.9884 | Horizontal Gene Transfer From Bacteria and Plants to the Arbuscular Mycorrhizal Fungus Rhizophagus irregularis. Arbuscular mycorrhizal fungi (AMF) belong to Glomeromycotina, and are mutualistic symbionts of many land plants. Associated bacteria accompany AMF during their lifecycle to establish a robust tripartite association consisting of fungi, plants and bacteria. Physical association among this trinity provides possibilities for the exchange of genetic materials. However, very few horizontal gene transfer (HGT) from bacteria or plants to AMF has been reported yet. In this study, we complement existing algorithms by developing a new pipeline, Blast2hgt, to efficiently screen for putative horizontally derived genes from a whole genome. Genome analyses of the glomeromycete Rhizophagus irregularis identified 19 fungal genes that had been transferred between fungi and bacteria/plants, of which seven were obtained from bacteria. Another 18 R. irregularis genes were found to be recently acquired from either plants or bacteria. In the R. irregularis genome, gene duplication has contributed to the expansion of three foreign genes. Importantly, more than half of the R. irregularis foreign genes were expressed in various transcriptomic experiments, suggesting that these genes are functional in R. irregularis. Functional annotation and available evidence showed that these acquired genes may participate in diverse but fundamental biological processes such as regulation of gene expression, mitosis and signal transduction. Our study suggests that horizontal gene influx through endosymbiosis is a source of new functions for R. irregularis, and HGT might have played a role in the evolution and symbiotic adaptation of this arbuscular mycorrhizal fungus. | 2018 | 29887874 |
| 290 | 6 | 0.9884 | Utility of the clostridial site-specific recombinase TnpX to clone toxic-product-encoding genes and selectively remove genomic DNA fragments. TnpX is a site-specific recombinase responsible for the excision and insertion of the transposons Tn4451 and Tn4453 in Clostridium perfringens and Clostridium difficile, respectively. Here, we exploit phenotypic features of TnpX to facilitate genetic mutagenesis and complementation studies. Genetic manipulation of bacteria often relies on the use of antibiotic resistance genes; however, a limited number are available for use in the clostridia. The ability of TnpX to recognize and excise specific DNA fragments was exploited here as the basis of an antibiotic resistance marker recycling system, specifically to remove antibiotic resistance genes from plasmids in Escherichia coli and from marked chromosomal C. perfringens mutants. This methodology enabled the construction of a C. perfringens plc virR double mutant by allowing the removal and subsequent reuse of the same resistance gene to construct a second mutation. Genetic complementation can be challenging when the gene of interest encodes a product toxic to E. coli. We show that TnpX represses expression from its own promoter, PattCI, which can be exploited to facilitate the cloning of recalcitrant genes in E. coli for subsequent expression in the heterologous host C. perfringens. Importantly, this technology expands the repertoire of tools available for the genetic manipulation of the clostridia. | 2014 | 24682304 |
| 338 | 7 | 0.9883 | Repair by genetic recombination in bacteria: overview. DNA molecules that have been damaged in both strands at the same level are not subject to repair by excision but instead can be repaired through recombination with homologous molecules. Examples of two-strand damage include postreplication gaps opposite pyrimidine dimers, two-strand breaks produced by X-rays, and chemically induced interstrand cross-links. In ultraviolet-irradiated bacteria, the newly synthesized DNA is of length equal to the interdimer spacing. With continued incubation, this low-molecular-weight DNA is joined into high-molecular-weight chains (postreplication repair), a process associated with sister exchanges in bacteria. Recombination is initiated by pyrimidine dimers opposite postreplication gaps and by interstrand cross-links that have been cut by excision enzymes. The free ends at the resulting gaps presumably initiate the exchanges. Postreplication repair in Escherichia coli occurs in recB- AND RECC but is greatly slowed in recF- mutants. RecB and recC are the structural genes for exonuclease V, which digests two-stranded DNA by releasing oligonucleotides first from one strand and then from the other. The postreplication sister exchanges in ultra-violet-irradiated bacteria result in the distribution of pyrimidine dimers between parental and daughter strands, indicating that long exchanges involving both strands of each duplex occur. The R1 restriction endonuclease from E. COli has been used to cut the DNA of a bacterial drug-resistance transfer factor with one nuclease-sensitive site, and also DNA from the frog Xenopus enriched for ribosomal 18S and 28S genes. The fragments were annealed with the cut plasmid DNA and ligated, producing a new larger plasmid carrying the eukaryotic rDNA and able to infect and replicate in E. coli. | 1975 | 1103833 |
| 9983 | 8 | 0.9883 | A new drug design strategy: Killing drug resistant bacteria by deactivating their hypothetical genes. Despite that a bacterial genome is complicated by large numbers of horizontally transferred (HT) genes and function unknown hypothetical (FUN) genes, the Genic-Transcriptional-Stop-Signals-Ratio (TSSR) of a genome shows that HT and FUN genes are complementary to all other genes in the genome. When HT or certain FUN genes are omitted from the Escherichia coli K-12 genome, its Genomic-TSSR value becomes totally incomparable to other E. coli strains. The Genic-TSSR correlation tree of a pathogen shows that some FUN genes would form a unique cluster. Removing these genes by site-specific mutation or gene-knockout should lead to the demise of this pathogen. | 2016 | 27901648 |
| 9982 | 9 | 0.9881 | Family 6 glycosyltransferases in vertebrates and bacteria: inactivation and horizontal gene transfer may enhance mutualism between vertebrates and bacteria. Glycosyltransferases (GTs) control the synthesis and structures of glycans. Inactivation and intense allelic variation in members of the GT6 family generate species-specific and individual variations in carbohydrate structures, including histo-blood group oligosaccharides, resulting in anti-glycan antibodies that target glycan-decorated pathogens. GT6 genes are ubiquitous in vertebrates but are otherwise rare, existing in a few bacteria, one protozoan, and cyanophages, suggesting lateral gene transfer. Prokaryotic GT6 genes correspond to one exon of vertebrate genes, yet their translated protein sequences are strikingly similar. Bacterial and phage GT6 genes influence the surface chemistry of bacteria, affecting their interactions, including those with vertebrate hosts. | 2010 | 20870714 |
| 9985 | 10 | 0.9881 | Identification of the First Gene Transfer Agent (GTA) Small Terminase in Rhodobacter capsulatus and Its Role in GTA Production and Packaging of DNA. Genetic exchange mediated by viruses of bacteria (bacteriophages) is the primary driver of rapid bacterial evolution. The priority of viruses is usually to propagate themselves. Most bacteriophages use the small terminase protein to identify their own genome and direct its inclusion into phage capsids. Gene transfer agents (GTAs) are descended from bacteriophages, but they instead package fragments of the entire bacterial genome without preference for their own genes. GTAs do not selectively target specific DNA, and no GTA small terminases are known. Here, we identified the small terminase from the model Rhodobacter capsulatus GTA, which then allowed prediction of analogues in other species. We examined the role of the small terminase in GTA production and propose a structural basis for random DNA packaging.IMPORTANCE Random transfer of any and all genes between bacteria could be influential in the spread of virulence or antimicrobial resistance genes. Discovery of the true prevalence of GTAs in sequenced genomes is hampered by their apparent similarity to bacteriophages. Our data allowed the prediction of small terminases in diverse GTA producer species, and defining the characteristics of a "GTA-type" terminase could be an important step toward novel GTA identification. Importantly, the GTA small terminase shares many features with its phage counterpart. We propose that the GTA terminase complex could become a streamlined model system to answer fundamental questions about double-stranded DNA (dsDNA) packaging by viruses that have not been forthcoming to date. | 2019 | 31534034 |
| 570 | 11 | 0.9881 | Genetic instability and methylation tolerance in colon cancer. Microsatellite instability was first identified in colon cancer and later shown to be due to mutations in genes responsible for correction of DNA mismatches. Several human mismatch correction genes that are homologous to those of yeast and bacteria have been identified and are mutated in families affected by the hereditary non-polyposis colorectal carcinoma (HNPCC) syndrome. Similar alterations have been also found in some sporadic colorectal cancers. The mismatch repair pathway corrects DNA replication errors and repair-defective colorectal carcinoma cell lines exhibit a generalized mutator phenotype. An additional consequence of mismatch repair defects is cellular resistance, or tolerance, to certain DNA damaging agents. | 1996 | 8967715 |
| 9073 | 12 | 0.9880 | EpitoCore: Mining Conserved Epitope Vaccine Candidates in the Core Proteome of Multiple Bacteria Strains. In reverse vaccinology approaches, complete proteomes of bacteria are submitted to multiple computational prediction steps in order to filter proteins that are possible vaccine candidates. Most available tools perform such analysis only in a single strain, or a very limited number of strains. But the vast amount of genomic data had shown that most bacteria contain pangenomes, i.e., their genomic information contains core, conserved genes, and random accessory genes specific to each strain. Therefore, in reverse vaccinology methods it is of the utmost importance to define core proteins and core epitopes. EpitoCore is a decision-tree pipeline developed to fulfill that need. It provides surfaceome prediction of proteins from related strains, defines core proteins within those, calculate their immunogenicity, predicts epitopes for a given set of MHC alleles defined by the user, and then reports if epitopes are located extracellularly and if they are conserved among the core homologs. Pipeline performance is illustrated by mining peptide vaccine candidates in Mycobacterium avium hominissuis strains. From a total proteome of ~4,800 proteins per strain, EpitoCore predicted 103 highly immunogenic core homologs located at cell surface, many of those related to virulence and drug resistance. Conserved epitopes identified among these homologs allows the users to define sets of peptides with potential to immunize the largest coverage of tested HLA alleles using peptide-based vaccines. Therefore, EpitoCore is able to provide automated identification of conserved epitopes in bacterial pangenomic datasets. | 2020 | 32431712 |
| 747 | 13 | 0.9880 | S51 Family Peptidases Provide Resistance to Peptidyl-Nucleotide Antibiotic McC. Microcin C (McC)-like compounds are natural Trojan horse peptide-nucleotide antibiotics produced by diverse bacteria. The ribosomally synthesized peptide parts of these antibiotics are responsible for their facilitated transport into susceptible cells. Once inside the cell, the peptide part is degraded, releasing the toxic payload, an isoaspartyl-nucleotide that inhibits aspartyl-tRNA synthetase, an enzyme essential for protein synthesis. Bacteria that produce microcin C-like compounds have evolved multiple ways to avoid self-intoxication. Here, we describe a new strategy through the action of S51 family peptidases, which we name MccG. MccG cleaves the toxic isoaspartyl-nucleotide, rendering it inactive. While some MccG homologs are encoded by gene clusters responsible for biosynthesis of McC-like compounds, most are encoded by standalone genes whose products may provide a basal level of resistance to peptide-nucleotide antibiotics in phylogenetically distant bacteria. IMPORTANCE Here, we identified a natural substrate for a major phylogenetic clade of poorly characterized S51 family proteases from bacteria. We show that these proteins can contribute to a basal level of resistance to an important class of natural antibiotics. | 2022 | 35467414 |
| 9980 | 14 | 0.9880 | A vector for the expression of recombinant monoclonal Fab fragments in bacteria. The availability of genes coding for monoclonal Fab fragments of a desired specificity permits their expression in bacteria and provides a simple method for the generation of good quality reagents. In this paper we describe a new phagemid vector for the production of recombinant Fabs from genes obtained from phage display combinatorial libraries. The phagemid features an antibiotic resistance cassette which, once inserted between the heavy chain fragment and the light chain genes, avoids unwanted recombination and preserves useful restriction sites not affecting the Fab production rate. | 1998 | 9776589 |
| 9367 | 15 | 0.9880 | Bacterial heterozygosity promotes survival under multidrug selection. Although bacterial cells typically contain a single chromosome, some species are naturally polyploid and carry multiple copies of their chromosome. Polyploid chromosomes can be identical or heterogeneous, the latter giving rise to bacterial heterozygosity. Although the benefits of heterozygosity are well studied in eukaryotes, its consequences in bacteria are less understood. Here, we examine this question in the context of antibiotic resistance to understand how bacterial genomic heterozygosity affects bacterial survival. Using a cell-wall-deficient model system in the actinomycete Kitasatospora viridifaciens, we found that heterozygous cells that contain different chromosomes expressing different antibiotic resistance markers persist across a broad range of antibiotic concentrations. Recombinant cells containing the same resistance genes on a single chromosome also survive these conditions, but these cells pay a significant fitness cost due to the constitutive expression of these genes. By contrast, heterozygous cells can mitigate these costs by flexibly adjusting the ratio of their different chromosomes, thereby allowing rapid responses in temporally and spatially variable environments. Our results provide evidence that bacterial heterozygosity can increase adaptive plasticity in bacterial cells in a similar manner to the evolutionary benefits provided by multicopy plasmids in bacteria. | 2025 | 40037350 |
| 453 | 16 | 0.9879 | Visualization of pathogenicity regions in bacteria. We show here how pathogenicity islands can be analysed using GenomeAtlases, which is a method for visualising repeats, DNA structural characteristics, and base composition of chromosomes and plasmids. We have applied this method to the E. coli plasmid pO157, and the Y. pestis plasmid pPCP1. In both cases pathogenic genes were shown to differ in A + T content and structural properties. Furthermore, examination of an antibiotic resistance gene cluster from S. typhimurium showed that the same was true for genes encoding antibiotic resistance. | 2000 | 11145420 |
| 348 | 17 | 0.9879 | Conjugative DNA transfer in Streptomyces by TraB: is one protein enough? Antibiotic-producing soil bacteria of the genus Streptomyces form a huge natural reservoir of antibiotic resistance genes for the dissemination within the soil community. Streptomyces plasmids encode a unique conjugative DNA transfer system clearly distinguished from classical conjugation involving a single-stranded DNA molecule and a type IV protein secretion system. Only a single plasmid-encoded protein, TraB, is sufficient to translocate a double-stranded DNA molecule into the recipient in Streptomyces matings. TraB is a hexameric pore-forming ATPase that resembles the chromosome segregator protein FtsK and translocates DNA by recognizing specific 8-bp repeats present in the plasmid clt locus. Mobilization of chromosomal genes does not require integration of the plasmid, because TraB also recognizes clt-like sequences distributed all over the chromosome. | 2012 | 23082971 |
| 9986 | 18 | 0.9879 | Identification and characterization of thousands of bacteriophage satellites across bacteria. Bacteriophage-bacteria interactions are affected by phage satellites, elements that exploit phages for transfer between bacteria. Satellites can encode defense systems, antibiotic resistance genes, and virulence factors, but their number and diversity are unknown. We developed SatelliteFinder to identify satellites in bacterial genomes, detecting the four best described families: P4-like, phage inducible chromosomal islands (PICI), capsid-forming PICI, and PICI-like elements (PLE). We vastly expanded the number of described elements to ∼5000, finding bacterial genomes with up to three different families of satellites. Most satellites were found in Proteobacteria and Firmicutes, but some are in novel taxa such as Actinobacteria. We characterized the gene repertoires of satellites, which are variable in size and composition, and their genomic organization, which is very conserved. Phylogenies of core genes in PICI and cfPICI indicate independent evolution of their hijacking modules. There are few other homologous core genes between other families of satellites, and even fewer homologous to phages. Hence, phage satellites are ancient, diverse, and probably evolved multiple times independently. Given the many bacteria infected by phages that still lack known satellites, and the recent proposals for novel families, we speculate that we are at the beginning of the discovery of massive numbers and types of satellites. | 2023 | 36869669 |
| 8268 | 19 | 0.9879 | Sustained coevolution of phage Lambda and Escherichia coli involves inner- as well as outer-membrane defences and counter-defences. Bacteria often evolve resistance to phage through the loss or modification of cell surface receptors. In Escherichia coli and phage λ, such resistance can catalyze a coevolutionary arms race focused on host and phage structures that interact at the outer membrane. Here, we analyse another facet of this arms race involving interactions at the inner membrane, whereby E. coli evolves mutations in mannose permease-encoding genes manY and manZ that impair λ's ability to eject its DNA into the cytoplasm. We show that these man mutants arose concurrently with the arms race at the outer membrane. We tested the hypothesis that λ evolved an additional counter-defence that allowed them to infect bacteria with deleted man genes. The deletions severely impaired the ancestral λ, but some evolved phage grew well on the deletion mutants, indicating that they regained infectivity by evolving the ability to infect hosts independently of the mannose permease. This coevolutionary arms race fulfils the model of an inverse gene-for-gene infection network. Taken together, the interactions at both the outer and inner membranes reveal that coevolutionary arms races can be richer and more complex than is often appreciated. | 2021 | 34032565 |