# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 4365 | 0 | 1.0000 | A diverse intrinsic antibiotic resistome from a cave bacterium. Antibiotic resistance is ancient and widespread in environmental bacteria. These are therefore reservoirs of resistance elements and reflective of the natural history of antibiotics and resistance. In a previous study, we discovered that multi-drug resistance is common in bacteria isolated from Lechuguilla Cave, an underground ecosystem that has been isolated from the surface for over 4 Myr. Here we use whole-genome sequencing, functional genomics and biochemical assays to reveal the intrinsic resistome of Paenibacillus sp. LC231, a cave bacterial isolate that is resistant to most clinically used antibiotics. We systematically link resistance phenotype to genotype and in doing so, identify 18 chromosomal resistance elements, including five determinants without characterized homologues and three mechanisms not previously shown to be involved in antibiotic resistance. A resistome comparison across related surface Paenibacillus affirms the conservation of resistance over millions of years and establishes the longevity of these genes in this genus. | 2016 | 27929110 |
| 4364 | 1 | 0.9998 | Antibiotic resistance is prevalent in an isolated cave microbiome. Antibiotic resistance is a global challenge that impacts all pharmaceutically used antibiotics. The origin of the genes associated with this resistance is of significant importance to our understanding of the evolution and dissemination of antibiotic resistance in pathogens. A growing body of evidence implicates environmental organisms as reservoirs of these resistance genes; however, the role of anthropogenic use of antibiotics in the emergence of these genes is controversial. We report a screen of a sample of the culturable microbiome of Lechuguilla Cave, New Mexico, in a region of the cave that has been isolated for over 4 million years. We report that, like surface microbes, these bacteria were highly resistant to antibiotics; some strains were resistant to 14 different commercially available antibiotics. Resistance was detected to a wide range of structurally different antibiotics including daptomycin, an antibiotic of last resort in the treatment of drug resistant Gram-positive pathogens. Enzyme-mediated mechanisms of resistance were also discovered for natural and semi-synthetic macrolide antibiotics via glycosylation and through a kinase-mediated phosphorylation mechanism. Sequencing of the genome of one of the resistant bacteria identified a macrolide kinase encoding gene and characterization of its product revealed it to be related to a known family of kinases circulating in modern drug resistant pathogens. The implications of this study are significant to our understanding of the prevalence of resistance, even in microbiomes isolated from human use of antibiotics. This supports a growing understanding that antibiotic resistance is natural, ancient, and hard wired in the microbial pangenome. | 2012 | 22509370 |
| 3871 | 2 | 0.9997 | Functional characterization of bacteria isolated from ancient arctic soil exposes diverse resistance mechanisms to modern antibiotics. Using functional metagenomics to study the resistomes of bacterial communities isolated from different layers of the Canadian high Arctic permafrost, we show that microbial communities harbored diverse resistance mechanisms at least 5,000 years ago. Among bacteria sampled from the ancient layers of a permafrost core, we isolated eight genes conferring clinical levels of resistance against aminoglycoside, β-lactam and tetracycline antibiotics that are naturally produced by microorganisms. Among these resistance genes, four also conferred resistance against amikacin, a modern semi-synthetic antibiotic that does not naturally occur in microorganisms. In bacteria sampled from the overlaying active layer, we isolated ten different genes conferring resistance to all six antibiotics tested in this study, including aminoglycoside, β-lactam and tetracycline variants that are naturally produced by microorganisms as well as semi-synthetic variants produced in the laboratory. On average, we found that resistance genes found in permafrost bacteria conferred lower levels of resistance against clinically relevant antibiotics than resistance genes sampled from the active layer. Our results demonstrate that antibiotic resistance genes were functionally diverse prior to the anthropogenic use of antibiotics, contributing to the evolution of natural reservoirs of resistance genes. | 2015 | 25807523 |
| 4508 | 3 | 0.9997 | Tetracycline Resistance Genes Identified from Distinct Soil Environments in China by Functional Metagenomics. Soil microbiota represents one of the ancient evolutionary origins of antibiotic resistance and has been increasingly recognized as a potentially vast unstudied reservoir of resistance genes with possibilities to exchange with pathogens. Tetracycline resistance is one of the most abundant antibiotic resistances that may transfer among clinical and commensal microorganisms. To investigate tetracycline resistance genes from soil bacteria in different habitats, we performed functional analysis of three metagenomic libraries derived from soil samples collected from Yunnan, Sichuan, and Tibet, respectively, in China. We found efflux transporter genes form all the libraries, including 21 major facilitator superfamily efflux pump genes and one multidrug and toxic compound extrusion (MATE) transporter gene. Interestingly, we also identified two tetracycline destructase genes, belonging to a newly described family of tetracycline-inactivating enzymes that scarcely observed in clinical pathogens, from the Tibet library. The inactivation activity of the putative enzyme was confirmed in vitro by biochemical analysis. Our results indicated that efflux pumps distributed predominantly across habitats. Meanwhile, the mechanism of enzymatic inactivation for tetracycline resistance should not be neglected and merits further investigation. | 2017 | 28790997 |
| 4153 | 4 | 0.9997 | Amino acid variation in the GyrA subunit of bacteria potentially associated with natural resistance to fluoroquinolone antibiotics. In studies of genetic diversity in natural microbial populations, we have analyzed nucleotide sequences in the quinolone resistance-determining region of the bacterial gyrA gene in ciprofloxacin-resistant and nonselected soil bacteria obtained from the environment. It is apparent that this sequence is highly variable, and resistance to fluoroquinolone antibiotics occurring in environmental populations of bacteria is due at least in part to natural sequence variation in this domain. We suggest that the development of new antimicrobial agents, including completely synthetic antimicrobials such as the fluoroquinolones, should incorporate the analysis of resistance mechanisms among microbes in natural environments; these studies could predict potential mechanisms of resistance to be encountered in subsequent clinical use of the agents and would guide chemical modification designed to evade resistance development. | 1997 | 9420056 |
| 4379 | 5 | 0.9997 | Drug resistance in Chromobacterium violaceum. Chromobacterium violaceum is a free-living bacterium commonly found in aquatic habitats of tropical and subtropical regions of the world. This bacterium is able to produce a large variety of products of biotechnological and pharmacological use. Although C. violaceum is considered to be non-pathogenic, some cases of severe infections in humans and other animals have been reported. Genomic data on the type strain ATCC 12472(T) has provided a comprehensive basis for detailed studies of pathogenicity, virulence and drug resistance genes. A large number of open reading frames associated with various mechanisms of drug resistance were found, comprising a remarkable feature of this organism. Amongst these, beta-lactam (penicillin and cephalosporin) and multidrug resistance genes (drug efflux pumps) were the most numerous. In addition, genes associated with bacitracin, bicyclomycin, chloramphenicol, kasugamycin, and methylenomycin were also found. It is postulated that these genes contribute to the ability of C. violaceum to compete with other bacteria in the environment, and also may help to explain the common drug resistance phenotypes observed in infections caused by this bacterium. | 2004 | 15100994 |
| 9648 | 6 | 0.9997 | The highly diverse Antarctic Peninsula soil microbiota as a source of novel resistance genes. The rise of multiresistant bacterial pathogens is currently one of the most critical threats to global health, encouraging a better understanding of the evolution and spread of antimicrobial resistance. In this regard, the role of the environment as a source of resistance mechanisms remains poorly understood. Moreover, we still know a minimal part of the microbial diversity and resistome present in remote and extreme environments, hosting microbes that evolved to resist harsh conditions and thus a potentially rich source of novel resistance genes. This work demonstrated that the Antarctic Peninsula soils host a remarkable microbial diversity and a widespread presence of autochthonous antibiotic-resistant bacteria and resistance genes. We observed resistance to a wide array of antibiotics among isolates, including Pseudomonas resisting ten or more different compounds, with an overall increased resistance in bacteria from non-intervened areas. In addition, genome analysis of selected isolates showed several genes encoding efflux pumps, as well as a lack of known resistance genes for some of the resisted antibiotics, including colistin, suggesting novel uncharacterized mechanisms. By combining metagenomic approaches based on analyzing raw reads, assembled contigs, and metagenome-assembled genomes, we found hundreds of widely distributed genes potentially conferring resistance to different antibiotics (including an outstanding variety of inactivation enzymes), metals, and biocides, hosted mainly by Polaromonas, Pseudomonas, Streptomyces, Variovorax, and Burkholderia. Furthermore, a proportion of these genes were found inside predicted plasmids and other mobile elements, including a putative OXA-like carbapenemase from Polaromonas harboring conserved key residues and predicted structural features. All this evidence indicates that the Antarctic Peninsula soil microbiota has a broad natural resistome, part of which could be transferred horizontally to pathogenic bacteria, acting as a potential source of novel resistance genes. | 2022 | 34856283 |
| 4151 | 7 | 0.9996 | Evolutionary relationships among genes for antibiotic resistance. The genes that determine resistance to antibiotics are commonly found encoded by extrachromosomal elements in bacteria. These were described first in Enterobacteriaceae and subsequently in a variety of other genera; their spread is associated with the increased use of antibiotics in human and animal medicine. Antibiotic-resistance genes that determine the production of enzymes which modify (detoxify) the antibiotics have been detected in antibiotic-producing organisms. It has been suggested that the producing strains provided the source of antibiotic-resistance genes that were then 'picked-up' by recombination. Recent studies of the nucleotide sequence of certain antibiotic-resistance genes indicate regions of strong homology in the encoded proteins. The implications of these similarities are discussed. | 1984 | 6559117 |
| 4663 | 8 | 0.9996 | Pan-genomics of Ochrobactrum species from clinical and environmental origins reveals distinct populations and possible links. Ochrobactrum genus is comprised of soil-dwelling Gram-negative bacteria mainly reported for bioremediation of toxic compounds. Since last few years, mainly two species of this genus, O. intermedium and O. anthropi were documented for causing infections mostly in the immunocompromised patients. Despite such ubiquitous presence, study of adaptation in various niches is still lacking. Thus, to gain insights into the niche adaptation strategies, pan-genome analysis was carried out by comparing 67 genome sequences belonging to Ochrobactrum species. Pan-genome analysis revealed it is an open pan-genome indicative of the continuously evolving nature of the genus. The presence/absence of gene clusters also illustrated the unique presence of antibiotic efflux transporter genes and type IV secretion system genes in the clinical strains while the genes of solvent resistance and exporter pumps in the environmental strains. A phylogenomic investigation based on 75 core genes depicted better and robust phylogenetic resolution and topology than the 16S rRNA gene. To support the pan-genome analysis, individual genomes were also investigated for the mobile genetic elements (MGE), antibiotic resistance genes (ARG), metal resistance genes (MRG) and virulence factors (VF). The analysis revealed the presence of MGE, ARG, and MRG in all the strains which play an important role in the species evolution which is in agreement with the pan-genome analysis. The average nucleotide identity (ANI) based on the genetic relatedness between the Ochrobactrum species indicated a distinction between individual species. Interestingly, the ANI tool was able to classify the Ochrobactrum genomes to the species level which were assigned till the genus level on the NCBI database. | 2020 | 32428556 |
| 4371 | 9 | 0.9996 | Independent origins and evolution of the secondary replicons of the class Gammaproteobacteria. Multipartite genomes, consisting of more than one replicon, have been found in approximately 10 % of bacteria, many of which belong to the phylum Proteobacteria. Many aspects of their origin and evolution, and the possible advantages related to this type of genome structure, remain to be elucidated. Here, we performed a systematic analysis of the presence and distribution of multipartite genomes in the class Gammaproteobacteria, which includes several genera with diverse lifestyles. Within this class, multipartite genomes are mainly found in the order Alteromonadales (mostly in the genus Pseudoalteromonas) and in the family Vibrionaceae. Our data suggest that the emergence of secondary replicons in Gammaproteobacteria is rare and that they derive from plasmids. Despite their multiple origins, we highlighted the presence of evolutionary trends such as the inverse proportionality of the genome to chromosome size ratio, which appears to be a general feature of bacteria with multipartite genomes irrespective of taxonomic group. We also highlighted some functional trends. The core gene set of the secondary replicons is extremely small, probably limited to essential genes or genes that favour their maintenance in the genome, while the other genes are less conserved. This hypothesis agrees with the idea that the primary advantage of secondary replicons could be to facilitate gene acquisition through horizontal gene transfer, resulting in replicons enriched in genes associated with adaptation to different ecological niches. Indeed, secondary replicons are enriched both in genes that could promote adaptation to harsh environments, such as those involved in antibiotic, biocide and metal resistance, and in functional categories related to the exploitation of environmental resources (e.g. carbohydrates), which can complement chromosomal functions. | 2023 | 37185344 |
| 4380 | 10 | 0.9996 | Comparative genome analysis of ciprofloxacin-resistant Pseudomonas aeruginosa reveals genes within newly identified high variability regions associated with drug resistance development. The alarming rise of ciprofloxacin-resistant Pseudomonas aeruginosa has been reported in several clinical studies. Though the mutation of resistance genes and their role in drug resistance has been researched, the process by which the bacterium acquires high-level resistance is still not well understood. How does the genomic evolution of P. aeruginosa affect resistance development? Could the exposure of antibiotics to the bacteria enrich genomic variants that lead to the development of resistance, and if so, how are these variants distributed through the genome? To answer these questions, we performed 454 pyrosequencing and a whole genome analysis both before and after exposure to ciprofloxacin. The comparative sequence data revealed 93 unique resistance strain variation sites, which included a mutation in the DNA gyrase subunit A gene. We generated variation-distribution maps comparing the wild and resistant types, and isolated 19 candidates from three discrete resistance-associated high variability regions that had available transposon mutants, to perform a ciprofloxacin exposure assay. Of these region candidates with transposon disruptions, 79% (15/19) showed a reduction in the ability to gain high-level resistance, suggesting that genes within these high variability regions might enrich for certain functions associated with resistance development. | 2013 | 23808957 |
| 4378 | 11 | 0.9996 | Gene network interaction analysis to elucidate the antimicrobial resistance mechanisms in the Clostridiumdifficile. Antimicrobial resistance has caused chaos worldwide due to the depiction of multidrug-resistant (MDR) infective microorganisms. A thorough examination of antimicrobial resistance (AMR) genes and associated resistant mechanisms is vital to solving this problem. Clostridium difficile (C. difficile) is an opportunistic nosocomial bacterial strain that has acquired exogenous AMR genes that confer resistance to antimicrobials such as erythromycin, azithromycin, clarithromycin, rifampicin, moxifloxacin, fluoroquinolones, vancomycin, and others. A network of interactions, including 20 AMR genes, was created and analyzed. In functional enrichment analysis, Cellular components (CC), Molecular Functions (MF), and Biological Processes (BP) were discovered to have substantial involvement. Mutations in the rpl genes, which encode ribosomal proteins, confer resistance in Gram-positive bacteria. Full erythromycin and azithromycin cross-resistance can be conferred if more than one of the abovementioned genes is present. In the enriched BP, rps genes related to transcriptional regulation and biosynthesis were found. The genes belong to the rpoB gene family, which has previously been related to rifampicin resistance. The genes rpoB, gyrA, gyrB, rpoS, rpl genes, rps genes, and Van genes are thought to be the hub genes implicated in resistance in C. difficile. As a result, new medications could be developed using these genes. Overall, our observations provide a thorough understanding of C. difficile AMR mechanisms. | 2023 | 36958645 |
| 9406 | 12 | 0.9996 | Proteomics as the final step in the functional metagenomics study of antimicrobial resistance. The majority of clinically applied antimicrobial agents are derived from natural products generated by soil microorganisms and therefore resistance is likely to be ubiquitous in such environments. This is supported by the fact that numerous clinically important resistance mechanisms are encoded within the genomes of such bacteria. Advances in genomic sequencing have enabled the in silico identification of putative resistance genes present in these microorganisms. However, it is not sufficient to rely on the identification of putative resistance genes, we must also determine if the resultant proteins confer a resistant phenotype. This will require an analysis pipeline that extends from the extraction of environmental DNA, to the identification and analysis of potential resistance genes and their resultant proteins and phenotypes. This review focuses on the application of functional metagenomics and proteomics to study antimicrobial resistance in diverse environments. | 2015 | 25784907 |
| 4265 | 13 | 0.9996 | Bacteriophages as vehicles of the resistome in cystic fibrosis. Environmental microbial communities and human microbiota represent a huge reservoir of mobilizable genes, the 'mobilome', including a pool of genes encoding antimicrobial resistance, the 'resistome'. Whole-genome sequencing of bacterial genomes from cystic fibrosis (CF) patients has demonstrated that bacteriophages contribute significantly to bacterial genome alterations, and metagenomic analysis of respiratory tract DNA viral communities has revealed the presence of genes encoding antimicrobial resistance in bacteriophages of CF patients. CF airways should now be considered as the site of complex microbiota, where bacteriophages are vehicles for the adaptation of bacteria to this specific environment and for the emergence and selection of multidrug-resistant bacteria with chimeric repertoires. As phages are already known to be mobilized during chronic infection of the lungs of patients with CF, it seems particularly important to improve the understanding of the mechanisms of phage induction to prevent the spread of virulence and/or antimicrobial resistance determinants within the CF population as well as in the community. Such a modern point of view may be a seminal reflection for clinical practice in the future since current antimicrobial therapy guidelines in the context of CF may lead to the emergence of genes encoding antimicrobial resistance. | 2011 | 21816766 |
| 3906 | 14 | 0.9996 | Survival in amoeba--a major selection pressure on the presence of bacterial copper and zinc resistance determinants? Identification of a "copper pathogenicity island". The presence of metal resistance determinants in bacteria usually is attributed to geological or anthropogenic metal contamination in different environments or associated with the use of antimicrobial metals in human healthcare or in agriculture. While this is certainly true, we hypothesize that protozoan predation and macrophage killing are also responsible for selection of copper/zinc resistance genes in bacteria. In this review, we outline evidence supporting this hypothesis, as well as highlight the correlation between metal resistance and pathogenicity in bacteria. In addition, we introduce and characterize the "copper pathogenicity island" identified in Escherichia coli and Salmonella strains isolated from copper- and zinc-fed Danish pigs. | 2015 | 26088177 |
| 4152 | 15 | 0.9996 | Quinolone resistance: much more than predicted. Since quinolones are synthetic antibiotics, it was predicted that mutations in target genes would be the only mechanism through which resistance could be acquired, because there will not be quinolone-resistance genes in nature. Contrary to this prediction, a variety of elements ranging from efflux pumps, target-protecting proteins, and even quinolone-modifying enzymes have been shown to contribute to quinolone resistance. The finding of some of these elements in plasmids indicates that quinolone resistance can be transferable. As a result, there has been a developing interest on the reservoirs for quinolone-resistance genes and on the potential risks associated with the use of these antibiotics in non-clinical environments. As a matter of fact, plasmid-encoded, quinolone-resistance qnr genes originated in the chromosome of aquatic bacteria. Thus the use of quinolones in fish-farming might constitute a risk for the emergence of resistance. Failure to predict the development of quinolone resistance reinforces the need of taking into consideration the wide plasticity of biological systems for future predictions. This plasticity allows pathogens to deal with toxic compounds, including those with a synthetic origin as quinolones. | 2011 | 21687414 |
| 4381 | 16 | 0.9996 | 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 |
| 8383 | 17 | 0.9996 | Novel insights into carbohydrate utilisation, antimicrobial resistance, and sporulation potential in Roseburia intestinalis isolates across diverse geographical locations. Roseburia intestinalis is one of the most abundant and important butyrate-producing human gut anaerobic bacteria that plays an important role in maintaining health and is a potential next-generation probiotic. We investigated the pangenome of 16 distinct strains, isolated over several decades, identifying local and time-specific adaptations. More than 50% of the genes in each individual strain were assigned to the core genome, and 77% of the cloud genes were unique to individual strains, revealing the high level of genome conservation. Co-carriage of the same enzymes involved in carbohydrate binding and degradation in all strains highlighted major pathways in carbohydrate utilization and reveal the importance of xylan, starch and mannose as key growth substrates. A single strain had adapted to use rhamnose as a sole growth substrate, the first time this has been reported. The ubiquitous presence of motility and sporulation gene clusters demonstrates the importance of these phenotypes for gut survival and acquisition of this bacterium. More than half the strains contained functional, potentially transferable, tetracycline resistance genes. This study advances our understanding of the importance of R. intestinalis within the gut ecosystem by elucidating conserved metabolic characteristics among different strains, isolated from different locations. This information will help to devise dietary strategies to increase the abundance of this species providing health benefits. | 2025 | 40089923 |
| 3877 | 18 | 0.9996 | Characterization of antibiotic resistance genes in the species of the rumen microbiota. Infections caused by multidrug resistant bacteria represent a therapeutic challenge both in clinical settings and in livestock production, but the prevalence of antibiotic resistance genes among the species of bacteria that colonize the gastrointestinal tract of ruminants is not well characterized. Here, we investigate the resistome of 435 ruminal microbial genomes in silico and confirm representative phenotypes in vitro. We find a high abundance of genes encoding tetracycline resistance and evidence that the tet(W) gene is under positive selective pressure. Our findings reveal that tet(W) is located in a novel integrative and conjugative element in several ruminal bacterial genomes. Analyses of rumen microbial metatranscriptomes confirm the expression of the most abundant antibiotic resistance genes. Our data provide insight into antibiotic resistange gene profiles of the main species of ruminal bacteria and reveal the potential role of mobile genetic elements in shaping the resistome of the rumen microbiome, with implications for human and animal health. | 2019 | 31748524 |
| 4671 | 19 | 0.9996 | Detection by metagenomic functional analysis and improvement by experimental evolution of β-lactams resistance genes present in oil contaminated soils. The spread of antibiotic resistance genes has become a global health concern identified by the World Health Organization as one of the greatest threats to health. Many of antimicrobial resistance determinants found in bacterial pathogens originate from environmental bacteria, so identifying the genes that confer resistance to antibiotics in different habitats is mandatory to better understand resistance mechanisms. Soil is one of the most diverse environments considered reservoir of antimicrobial resistance genes. The aim of this work is to study the presence of genes that provide resistance to antibiotics used in clinical settings in two oil contaminated soils by metagenomic functional analysis. Using fosmid vectors that efficiently transcribe metagenomic DNA, we have selected 12 fosmids coding for two class A β-lactamases, two subclass B1 and two subclass B3 metallo-β-lactamases, one class D β-lactamase and three efflux pumps that confer resistance to cefexime, ceftriaxone, meropenem and/or imipenem. In some of them, detection of the resistance required heterologous expression from the fosmid promoter. Although initially, these environmental genes only provide resistance to low concentrations of antibiotics, we have obtained, by experimental evolution, fosmid derivatives containing β-lactamase ORFs with a single base substitution, which substantially increase their β-lactamase activity and resistance level. None of the mutations affect β-lactamase coding sequences and are all located upstream of them. These results demonstrate the presence of enzymes that confer resistance to relevant β-lactams in these soils and their capacity to rapidly adapt to provide higher resistance levels. | 2022 | 35768448 |