# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 8238 | 0 | 0.9627 | Resistance to enediyne antitumor antibiotics by CalC self-sacrifice. Antibiotic self-resistance mechanisms, which include drug elimination, drug modification, target modification, and drug sequestration, contribute substantially to the growing problem of antibiotic resistance among pathogenic bacteria. Enediynes are among the most potent naturally occurring antibiotics, yet the mechanism of resistance to these toxins has remained a mystery. We characterize an enediyne self-resistance protein that reveals a self-sacrificing paradigm for resistance to highly reactive antibiotics, and thus another opportunity for nonpathogenic or pathogenic bacteria to evade extremely potent small molecules. | 2003 | 12970566 |
| 570 | 1 | 0.9626 | 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 |
| 8363 | 2 | 0.9623 | Hundreds of antimicrobial peptides create a selective barrier for insect gut symbionts. The spatial organization of gut microbiota is crucial for the functioning of the gut ecosystem, although the mechanisms that organize gut bacterial communities in microhabitats are only partially understood. The gut of the insect Riptortus pedestris has a characteristic microbiota biogeography with a multispecies community in the anterior midgut and a monospecific bacterial population in the posterior midgut. We show that the posterior midgut region produces massively hundreds of specific antimicrobial peptides (AMPs), the Crypt-specific Cysteine-Rich peptides (CCRs) that have membrane-damaging antimicrobial activity against diverse bacteria but posterior midgut symbionts have elevated resistance. We determined by transposon-sequencing the genetic repertoire in the symbiont Caballeronia insecticola to manage CCR stress, identifying different independent pathways, including AMP-resistance pathways unrelated to known membrane homeostasis functions as well as cell envelope functions. Mutants in the corresponding genes have reduced capacity to colonize the posterior midgut, demonstrating that CCRs create a selective barrier and resistance is crucial in gut symbionts. Moreover, once established in the gut, the bacteria differentiate into a CCR-sensitive state, suggesting a second function of the CCR peptide arsenal in protecting the gut epithelia or mediating metabolic exchanges between the host and the gut symbionts. Our study highlights the evolution of an extreme diverse AMP family that likely contributes to establish and control the gut microbiota. | 2024 | 38865264 |
| 8183 | 3 | 0.9623 | Modification of arthropod vector competence via symbiotic bacteria. Some of the world's most devastating diseases are transmitted by arthropod vectors. Attempts to control these arthropods are currently being challenged by the widespread appearance of insecticide resistance. It is therefore desirable to develop alternative strategies to complement existing methods of vector control. In this review, Charles Beard, Scott O'Neill, Robert Tesh, Frank Richards and Serap Aksoy present an approach for introducing foreign genes into insects in order to confer refractoriness to vector populations, ie. the inability to transmit disease-causing agents. This approach aims to express foreign anti-parasitic or anti-viral gene products in symbiotic bacteria harbored by insects. The potential use of naturally occurring symbiont-based mechanisms in the spread of such refractory phenotypes is also discussed. | 1993 | 15463748 |
| 567 | 4 | 0.9622 | A novel bipartite antitermination system widespread in conjugative elements of Gram-positive bacteria. Transcriptional regulation allows adaptive and coordinated gene expression, and is essential for life. Processive antitermination systems alter the transcription elongation complex to allow the RNA polymerase to read through multiple terminators in an operon. Here, we describe the discovery of a novel bipartite antitermination system that is widespread among conjugative elements from Gram-positive bacteria, which we named conAn. This system is composed of a large RNA element that exerts antitermination, and a protein that functions as a processivity factor. Besides allowing coordinated expression of very long operons, we show that these systems allow differential expression of genes within an operon, and probably contribute to strict regulation of the conjugation genes by minimizing the effects of spurious transcription. Mechanistic features of the conAn system are likely to decisively influence its host range, with important implications for the spread of antibiotic resistance and virulence genes. | 2021 | 33999173 |
| 9173 | 5 | 0.9621 | Bacterial defences: mechanisms, evolution and antimicrobial resistance. Throughout their evolutionary history, bacteria have faced diverse threats from other microorganisms, including competing bacteria, bacteriophages and predators. In response to these threats, they have evolved sophisticated defence mechanisms that today also protect bacteria against antibiotics and other therapies. In this Review, we explore the protective strategies of bacteria, including the mechanisms, evolution and clinical implications of these ancient defences. We also review the countermeasures that attackers have evolved to overcome bacterial defences. We argue that understanding how bacteria defend themselves in nature is important for the development of new therapies and for minimizing resistance evolution. | 2023 | 37095190 |
| 8362 | 6 | 0.9618 | Lifestyle evolution in symbiotic bacteria: insights from genomics. Bacteria that live only in eukaryotic cells and tissues, including chronic pathogens and mutualistic bacteriocyte associates, often possess a distinctive set of genomic traits, including reduced genome size, biased nucleotide base composition and fast polypeptide evolution. These phylogenetically diverse bacteria have lost certain functional categories of genes, including DNA repair genes, which affect mutational patterns. However, pathogens and mutualistic symbionts retain loci that underlie their unique interaction types, such as genes enabling nutrient provisioning by mutualistic bacteria-inhabiting animals. Recent genomic studies suggest that many of these bacteria are irreversibly specialized, precluding shifts between pathogenesis and mutualism. | 2000 | 10884696 |
| 9195 | 7 | 0.9616 | Complement-resistance mechanisms of bacteria. Despite more than a century of parallel research on bacteria and the complement system, relatively little is known of the mechanisms whereby pathogenic bacteria can escape complement-related opsonophagocytosis and direct killing. It is likely that pathogenicity in bacteria has arisen more accidentally than in viruses, and on the basis of selection from natural mutants rather than by outright stealing or copying of genetic codes from the host. In this review we will discuss complement resistance as one of the features that makes a bacterium a pathogen. | 1999 | 10816084 |
| 9316 | 8 | 0.9616 | Molecular basis of metronidazole resistance in pathogenic bacteria and protozoa. The molecular basis of metronidazole resistance has been examined in anaerobic bacteria, such as Bacteroides, Clostridium, and Helicobacter, and anaerobic parasitic protists such as Giardia, Entamoeba, and trichomonads. A variety of enzymatic and cellular alterations have been shown to correlate with metronidazole susceptibility in these pathogens; however, a common theme has been revealed. Resistant cells are typically deficient in drug activation. The frequent correlation between metronidazole resistance and ineffective drug activation suggests that drug resistance is the result of modification of proteins involved in drug activation. Copyright 1999 Harcourt Publishers Ltd. | 1999 | 11504503 |
| 8235 | 9 | 0.9614 | The bacterial defense system MADS interacts with CRISPR-Cas to limit phage infection and escape. The constant arms race between bacteria and their parasites has resulted in a large diversity of bacterial defenses, with many bacteria carrying multiple systems. Here, we report the discovery of a phylogenetically widespread defense system, coined methylation-associated defense system (MADS), which is distributed across gram-positive and gram-negative bacteria. MADS interacts with a CRISPR-Cas system in its native host to provide robust and durable resistance against phages. While phages can acquire epigenetic-mediated resistance against MADS, co-existence of MADS and a CRISPR-Cas system limits escape emergence. MADS comprises eight genes with predicted nuclease, ATPase, kinase, and methyltransferase domains, most of which are essential for either self/non-self discrimination, DNA restriction, or both. The complex genetic architecture of MADS and MADS-like systems, relative to other prokaryotic defenses, points toward highly elaborate mechanisms of sensing infections, defense activation, and/or interference. | 2024 | 39094583 |
| 9984 | 10 | 0.9614 | Multiplex base editing to convert TAG into TAA codons in the human genome. Whole-genome recoding has been shown to enable nonstandard amino acids, biocontainment and viral resistance in bacteria. Here we take the first steps to extend this to human cells demonstrating exceptional base editing to convert TAG to TAA for 33 essential genes via a single transfection, and examine base-editing genome-wide (observing ~40 C-to-T off-target events in essential gene exons). We also introduce GRIT, a computational tool for recoding. This demonstrates the feasibility of recoding, and highly multiplex editing in mammalian cells. | 2022 | 35918324 |
| 333 | 11 | 0.9613 | 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 |
| 9330 | 12 | 0.9613 | Pneumococcal Extracellular Vesicles Mediate Horizontal Gene Transfer via the Transformation Machinery. Bacterial cells secrete extracellular vesicles (EVs), the function of which is a matter of intense investigation. Here, we show that the EVs secreted by the human pathogen Streptococcus pneumoniae (pneumococcus) are associated with bacterial DNA on their surface and can deliver this DNA to the transformation machinery of competent cells. These findings suggest that EVs contribute to gene transfer in Gram-positive bacteria, and in doing so, may promote the spread of drug resistance genes in the population. | 2023 | 38168155 |
| 8355 | 13 | 0.9613 | Ecology-relevant bacteria drive the evolution of host antimicrobial peptides in Drosophila. Antimicrobial peptides are host-encoded immune effectors that combat pathogens and shape the microbiome in plants and animals. However, little is known about how the host antimicrobial peptide repertoire is adapted to its microbiome. Here, we characterized the function and evolution of the Diptericin antimicrobial peptide family of Diptera. Using mutations affecting the two Diptericins (Dpt) of Drosophila melanogaster, we reveal the specific role of DptA for the pathogen Providencia rettgeri and DptB for the gut mutualist Acetobacter. The presence of DptA- or DptB-like genes across Diptera correlates with the presence of Providencia and Acetobacter in their environment. Moreover, DptA- and DptB-like sequences predict host resistance against infection by these bacteria across the genus Drosophila. Our study explains the evolutionary logic behind the bursts of rapid evolution of an antimicrobial peptide family and reveals how the host immune repertoire adapts to changing microbial environments. | 2023 | 37471548 |
| 8139 | 14 | 0.9612 | TAL effectors: highly adaptable phytobacterial virulence factors and readily engineered DNA-targeting proteins. Transcription activator-like (TAL) effectors are transcription factors injected into plant cells by pathogenic bacteria of the genus Xanthomonas. They function as virulence factors by activating host genes important for disease, or as avirulence factors by turning on genes that provide resistance. DNA-binding specificity is encoded by polymorphic repeats in each protein that correspond one-to-one with different nucleotides. This code has facilitated target identification and opened new avenues for engineering disease resistance. It has also enabled TAL effector customization for targeted gene control, genome editing, and other applications. This article reviews the structural basis for TAL effector-DNA specificity, the impact of the TAL effector-DNA code on plant pathology and engineered resistance, and recent accomplishments and future challenges in TAL effector-based DNA targeting. | 2013 | 23707478 |
| 8327 | 15 | 0.9611 | 'Big things in small packages: the genetics of filamentous phage and effects on fitness of their host'. This review synthesizes recent and past observations on filamentous phages and describes how these phages contribute to host phentoypes. For example, the CTXφ phage of Vibrio cholerae encodes the cholera toxin genes, responsible for causing the epidemic disease, cholera. The CTXφ phage can transduce non-toxigenic strains, converting them into toxigenic strains, contributing to the emergence of new pathogenic strains. Other effects of filamentous phage include horizontal gene transfer, biofilm development, motility, metal resistance and the formation of host morphotypic variants, important for the biofilm stress resistance. These phages infect a wide range of Gram-negative bacteria, including deep-sea, pressure-adapted bacteria. Many filamentous phages integrate into the host genome as prophage. In some cases, filamentous phages encode their own integrase genes to facilitate this process, while others rely on host-encoded genes. These differences are mediated by different sets of 'core' and 'accessory' genes, with the latter group accounting for some of the mechanisms that alter the host behaviours in unique ways. It is increasingly clear that despite their relatively small genomes, these phages exert signficant influence on their hosts and ultimately alter the fitness and other behaviours of their hosts. | 2015 | 25670735 |
| 8625 | 16 | 0.9610 | Marine viruses: truth or dare. Over the past two decades, marine virology has progressed from a curiosity to an intensely studied topic of critical importance to oceanography. At concentrations of approximately 10 million viruses per milliliter of surface seawater, viruses are the most abundant biological entities in the oceans. The majority of these viruses are phages (viruses that infect bacteria). Through lysing their bacterial hosts, marine phages control bacterial abundance, affect community composition, and impact global biogeochemical cycles. In addition, phages influence their hosts through selection for resistance, horizontal gene transfer, and manipulation of bacterial metabolism. Recent work has also demonstrated that marine phages are extremely diverse and can carry a variety of auxiliary metabolic genes encoding critical ecological functions. This review is structured as a scientific "truth or dare," revealing several well-established "truths" about marine viruses and presenting a few "dares" for the research community to undertake in future studies. | 2012 | 22457982 |
| 8423 | 17 | 0.9610 | 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 |
| 9341 | 18 | 0.9610 | Horizontal gene transfers in insects. Horizontal gene transfer is the transfer of genetic material across species boundaries. Although horizontal gene transfers are relatively rare in animals, the recent rapid accumulation of genomic data has identified increasing amounts of exogenous DNA inserts in insect genomes. Most of the horizontally acquired sequences appear to be non-functional; however, there is growing evidence that some genes are truly expressed and confer novel functions on the recipient insects. These include previously unavailable metabolic properties including digesting food, degrading toxins, providing resistance to pathogens, and facilitating an obligate mutualistic relationship with intracellular bacteria. A recent analysis revealed that an aphid gene of bacterial origin encodes a protein that is transported into the obligate symbiont, paralleling the evolution of endosymbiotic organelles. | 2015 | 32131363 |
| 611 | 19 | 0.9608 | The Staphylococcus aureus FASII bypass escape route from FASII inhibitors. Antimicrobials targeting the fatty acid synthesis (FASII) pathway are being developed as alternative treatments for bacterial infections. Emergence of resistance to FASII inhibitors was mainly considered as a consequence of mutations in the FASII target genes. However, an alternative and efficient anti-FASII resistance strategy, called here FASII bypass, was uncovered. Bacteria that bypass FASII incorporate exogenous fatty acids in membrane lipids, and thus dispense with the need for FASII. This strategy is used by numerous Gram-positive low GC % bacteria, including streptococci, enterococci, and staphylococci. Some bacteria repress FASII genes once fatty acids are available, and "constitutively" shift to FASII bypass. Others, such as the major pathogen Staphylococcus aureus, can undergo high frequency mutations that favor FASII bypass. This capacity is particularly relevant during infection, as the host supplies the fatty acids needed for bacteria to bypass FASII and thus become resistant to FASII inhibitors. Screenings for anti-FASII resistance in the presence of exogenous fatty acids confirmed that FASII bypass confers anti-FASII resistance among clinical and veterinary isolates. Polymorphisms in S. aureus FASII initiation enzymes favor FASII bypass, possibly by increasing availability of acyl-carrier protein, a required intermediate. Here we review FASII bypass and consequences in light of proposed uses of anti-FASII to treat infections, with a focus on FASII bypass in S. aureus. | 2017 | 28728970 |