An updated phylogeny of the metallo-β-lactamases

2020 ◽  
Vol 76 (1) ◽  
pp. 117-123
Author(s):  
Fanny Berglund ◽  
Anna Johnning ◽  
D G Joakim Larsson ◽  
Erik Kristiansson
Keyword(s):  
Binding Sites ◽  
Phylogenetic Trees ◽  
Pathogenic Bacteria ◽  
Gene Families ◽  
Zinc Binding ◽  
Metagenomic Data ◽  
Phylogenetic Groups ◽  
Taxonomic Organization ◽  
Almost All ◽  
Functional Profiles

Abstract Background Metallo-β-lactamases (MBLs) are enzymes that use zinc-dependent hydrolysis to confer resistance to almost all available β-lactam antibiotics. They are hypothesized to originate from commensal and environmental bacteria, from where some have mobilized and transferred horizontally to pathogens. The current phylogeny of MBLs, however, is biased as it is founded largely on genes encountered in pathogenic bacteria. This incompleteness is emphasized by recent findings of environmental MBLs with new forms of zinc binding sites and atypical functional profiles. Objectives To expand the phylogeny of MBLs to provide a more accurate view of their evolutionary history. Methods We searched more than 16 terabases of genomic and metagenomic data for MBLs of the three subclasses B1, B2 and B3 using the validated fARGene method. Predicted genes, together with the previously known ones, were used to infer phylogenetic trees. Results We identified 2290 unique MBL genes forming 817 gene families, of which 741 were previously uncharacterized. MBLs from subclasses B1 and B3 separated into distinct monophyletic groups, in agreement with their taxonomic and functional properties. We present evidence that clinically associated MBLs were mobilized from Proteobacteria. Additionally, we identified three new variants of the zinc binding sites, indicating that the functional repertoire is broader than previously reported. Conclusions Based on our results, we recommend that the nomenclature of MBLs is refined into the phylogenetic groups B1.1–B1.5 and B3.1–B3.4 that more accurately describe their molecular and functional characteristics. Our results will also facilitate the annotation of novel MBLs, reflecting their taxonomic organization and evolutionary origin.

scholarly journals Investigation of Two Evolutionarily Unrelated Halocarboxylic Acid Dehalogenase Gene Families

1999 ◽  
Vol 181 (8) ◽  
pp. 2535-2547 ◽  
Author(s):  
Katja E. Hill ◽  
Julian R. Marchesi ◽  
Andrew J. Weightman
Keyword(s):  
Amino Acid ◽  
Molecular Analysis ◽  
Phylogenetic Trees ◽  
Gene Families ◽  
Amino Acid Sequences ◽  
Group I ◽  
Silent Genes ◽  
Degrading Bacteria ◽  
Group Ii ◽  
Almost All

ABSTRACT Dehalogenases are key enzymes in the metabolism of halo-organic compounds. This paper describes a systematic approach to the isolation and molecular analysis of two families of bacterial α-halocarboxylic acid (αHA) dehalogenase genes, called group I and group II deh genes. The two families are evolutionarily unrelated and together represent almost all of the αHAdeh genes described to date. We report the design and evaluation of degenerate PCR primer pairs for the separate amplification and isolation of group I and II dehgenes. Amino acid sequences derived from 10 of 11 group Ideh partial gene products of new and previously reported bacterial isolates showed conservation of five residues previously identified as essential for activity. The exception, DehD from a Rhizobium sp., had only two of these five residues. Group II deh gene sequences were amplified from 54 newly isolated strains, and seven of these sequences were cloned and fully characterized. Group II dehalogenases were stereoselective, dechlorinating l- but not d-2-chloropropionic acid, and derived amino acid sequences for all of the genes exceptdehII°P11 showed conservation of previously identified essential residues. Molecular analysis of the twodeh families highlighted four subdivisions in each, which were supported by high bootstrap values in phylogenetic trees and by enzyme structure-function considerations. Group Ideh genes included two putative cryptic or silent genes, dehI°PP3 anddehI°17a, produced by different organisms. Group II deh genes included two cryptic genes and an active gene, dehII PP3, that can be switched off and on. All αHA-degrading bacteria so far described were Proteobacteria, a result that may be explained by limitations either in the host range fordeh genes or in isolation methods.

scholarly journals The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tengcheng Que ◽  
Huifeng Wang ◽  
Weifei Yang ◽  
Jianbao Wu ◽  
Chenyang Hou ◽  
...  
Keyword(s):  
De Novo ◽  
Great Majority ◽  
Gene Families ◽  
Functional Enrichment ◽  
Mineral Absorption ◽  
Iron Storage ◽  
Trachypithecus Leucocephalus ◽  
Karst Environment ◽  
Alkali Tolerance ◽  
Almost All

Abstract Background Trachypithecus leucocephalus, the white-headed langur, is a critically endangered primate that is endemic to the karst mountains in the southern Guangxi province of China. Studying the genomic and transcriptomic mechanisms underlying its local adaptation could help explain its persistence within a highly specialized ecological niche. Results In this study, we used PacBio sequencing and optical assembly and Hi-C analysis to create a high-quality de novo assembly of the T. leucocephalus genome. Annotation and functional enrichment revealed many genes involved in metabolism, transport, and homeostasis, and almost all of the positively selected genes were related to mineral ion binding. The transcriptomes of 12 tissues from three T. leucocephalus individuals showed that the great majority of genes involved in mineral absorption and calcium signaling were expressed, and their gene families were significantly expanded. For example, FTH1 primarily functions in iron storage and had 20 expanded copies. Conclusions These results increase our understanding of the evolution of alkali tolerance and other traits necessary for the persistence of T. leucocephalus within an ecologically unique limestone karst environment.

scholarly journals Isolation and Characterization of Bacteriophage ZCSE6 against Salmonella spp.: Phage Application in Milk

Biologics ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 164-176
Author(s):  
Abdallah S. Abdelsattar ◽  
Anan Safwat ◽  
Rana Nofal ◽  
Amera Elsayed ◽  
Salsabil Makky ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Raw Milk ◽  
Salmonella Spp ◽  
Isolation And Characterization ◽  
Food Borne ◽  
Wide Range ◽  
Almost All ◽  
And Control ◽  
Milk And Dairy Products

Food safety is very important in the food industry as most pathogenic bacteria can cause food-borne diseases and negatively affect public health. In the milk industry, contamination with Salmonella has always been a challenge, but the risks have dramatically increased as almost all bacteria now show resistance to a wide range of commercial antibiotics. This study aimed to isolate a bacteriophage to be used as a bactericidal agent against Salmonella in milk and dairy products. Here, phage ZCSE6 has been isolated from raw milk sample sand molecularly and chemically characterized. At different multiplicities of infection (MOIs) of 0.1, 0.01, and 0.001, the phage–Salmonella interaction was studied for 6 h at 37 °C and 24 h at 8 °C. In addition, ZCSE6 was tested against Salmonella contamination in milk to examine its lytic activity for 3 h at 37 °C. The results showed that ZCSE6 has a small genome size (<48.5 kbp) and belongs to the Siphovirus family. Phage ZCSE6 revealed a high thermal and pH stability at various conditions that mimic milk manufacturing and supply chain conditions. It also demonstrated a significant reduction in Salmonella concentration in media at various MOIs, with higher bacterial eradication at higher MOI. Moreover, it significantly reduced Salmonella growth (MOI 1) in milk, manifesting a 1000-fold decrease in bacteria concentration following 3 h incubation at 37 °C. The results highlighted the strong ability of ZCSE6 to kill Salmonella and control its growth in milk. Thus, ZCSE6 is recommended as a biocontrol agent in milk to limit bacterial growth and increase the milk shelf-life.

Sex difference in the cytosolic and nuclear distribution of androgen receptor in mouse submandibular gland

1986 ◽  
Vol 108 (2) ◽  
pp. 267-273 ◽  
Author(s):  
S. Kyakumoto ◽  
R. Kurokawa ◽  
Y. Ohara-Nemoto ◽  
M. Ota
Keyword(s):  
Androgen Receptor ◽  
Nuclear Receptors ◽  
Binding Sites ◽  
Androgen Receptors ◽  
Dissociation Constants ◽  
Scatchard Analysis ◽  
Male And Female ◽  
Short Period ◽  
Almost All ◽  
Androgen Binding

ABSTRACT Cytosol and nuclear androgen receptors in submandibular glands of male and female mice were measured by an exchange assay at 0 °C. The binding of [3H]methyltrienolone to cytosol receptors in females was mostly saturated within a short period of incubation (3 h), whereas the saturation was much slower in males; suggesting that almost all of the cytosol receptors were unoccupied in females and the receptors were partially occupied in males. Nuclear receptors were extracted with pyridoxal 5′-phosphate (5 mmol/l) from nuclear fractions with 93–95% efficiency. The exchange of the bound steroids occurred by 24–48 h at 0 °C, suggesting that most of the nuclear androgen receptor was occupied. The binding was low at higher temperatures, probably due to inactivation of the receptor. Scatchard analysis showed that the apparent dissociation constants of cytosol and nuclear receptors were similar (0·8 and 0·9 nmol/l respectively) in both sexes. On the other hand, the number of androgen-binding sites in the nucleus was much higher in males than in females (1052 fmol/mg DNA and 32 fmol/mg DNA respectively), while the number in the cytosol was higher in females than in males (512 fmol/mg DNA and 368 fmol/mg DNA respectively). These observations show that androgen receptors exist mainly (74%) in the nuclei of males, while they exist mostly (94%) in the cytosol of females. J. Endocr. (1986) 108, 267–273

ZincExplorer: an accurate hybrid method to improve the prediction of zinc-binding sites from protein sequences

2013 ◽  
Vol 9 (9) ◽  
pp. 2213 ◽  
Author(s):  
Zhen Chen ◽  
Yanying Wang ◽  
Ya-Feng Zhai ◽  
Jiangning Song ◽  
Ziding Zhang
Keyword(s):  
Hybrid Method ◽  
Binding Sites ◽  
Protein Sequences ◽  
Zinc Binding

scholarly journals Phylogenetic Grouping and Virulence Potential of Extended-Spectrum-β-Lactamase-Producing Escherichia coli Strains in Cattle

2012 ◽  
Vol 78 (13) ◽  
pp. 4677-4682 ◽  
Author(s):  
Charlotte Valat ◽  
Frédéric Auvray ◽  
Karine Forest ◽  
Véronique Métayer ◽  
Emilie Gay ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Virulence Determinants ◽  
Phylogenetic Groups ◽  
Content Type ◽  
E Coli ◽  
Extended Spectrum ◽  
Specific Distribution ◽  
Extended Spectrum Beta Lactamases ◽  
Phylogenetic Grouping ◽  
Almost All

ABSTRACTIn line with recent reports of extended-spectrum beta-lactamases (ESBLs) inEscherichia coliisolates of highly virulent serotypes, such as O104:H4, we investigated the distribution of phylogroups (A, B1, B2, D) and virulence factor (VF)-encoding genes in 204 ESBL-producingE. coliisolates from diarrheic cattle. ESBL genes, VFs, and phylogroups were identified by PCR and a commercial DNA array (Alere, France). ESBL genes belonged mostly to the CTX-M-1 (65.7%) and CTX-M-9 (27.0%) groups, whereas those of the CTX-M-2 and TEM groups were much less represented (3.9% and 3.4%, respectively). One ESBL isolate wasstx1andeaepositive and belonged to a major enterohemorrhagicE. coli(EHEC) serotype (O111:H8). Two other isolates wereeaepositive butstxnegative; one of these had serotype O26:H11. ESBL isolates belonged mainly to phylogroup A (55.4%) and, to lesser extents, to phylogroups D (25.5%) and B1 (15.6%), whereas B2 strains were quasi-absent (1/204). The number of VFs was significantly higher in phylogroup B1 than in phylogroups A (P= 0.04) and D (P= 0.02). Almost all of the VFs detected were found in CTX-M-1 isolates, whereas only 64.3% and 33.3% of them were found in CTX-M-9 and CTX-M-2 isolates, respectively. These results indicated that the widespread dissemination of theblaCTX-Mgenes within theE. colipopulation from cattle still spared the subpopulation of EHEC/Shiga-toxigenicE. coli(STEC) isolates. In contrast to other reports on non-ESBL-producing isolates from domestic animals, B1 was not the main phylogroup identified. However, B1 was found to be the most virulent phylogroup, suggesting host-specific distribution of virulence determinants among phylogenetic groups.

scholarly journals Fibrinolysis: A Primordial System Linked to the Immune Response

2021 ◽  
Vol 22 (7) ◽  
pp. 3406
Author(s):  
Robert L. Medcalf ◽  
Charithani B. Keragala
Keyword(s):  
Binding Sites ◽  
Defense Mechanisms ◽  
Immune Cell ◽  
Immune Defense ◽  
Surface Proteins ◽  
Cell Behavior ◽  
Phylogenetic Studies ◽  
Blood Clots ◽  
Lower Vertebrates ◽  
Almost All

The fibrinolytic system provides an essential means to remove fibrin deposits and blood clots. The actual protease responsible for this is plasmin, formed from its precursor, plasminogen. Fibrin is heralded as it most renowned substrate but for many years plasmin has been known to cleave many other substrates, and to also activate other proteolytic systems. Recent clinical studies have shown that the promotion of plasmin can lead to an immunosuppressed phenotype, in part via its ability to modulate cytokine expression. Almost all immune cells harbor at least one of a dozen plasminogen receptors that allows plasmin formation on the cell surface that in turn modulates immune cell behavior. Similarly, a multitude of pathogens can also express their own plasminogen activators, or contain surface proteins that provide binding sites host plasminogen. Plasmin formed under these circumstances also empowers these pathogens to modulate host immune defense mechanisms. Phylogenetic studies have revealed that the plasminogen activating system predates the appearance of fibrin, indicating that plasmin did not evolve as a fibrinolytic protease but perhaps has its roots as an immune modifying protease. While its fibrin removing capacity became apparent in lower vertebrates these primitive under-appreciated immune modifying functions still remain and are now becoming more recognised.

scholarly journals Two Populations of Glucocorticoid Receptor-Binding Sites in the Male Rat Hippocampal Genome

Endocrinology ◽  
2013 ◽  
Vol 154 (5) ◽  
pp. 1832-1844 ◽  
Author(s):  
J. Annelies E. Polman ◽  
E. Ronald de Kloet ◽  
Nicole A. Datson
Keyword(s):  
Receptor Binding ◽  
Binding Sites ◽  
Glucocorticoid Receptors ◽  
Full Range ◽  
Male Rat ◽  
Motif Analysis ◽  
Wide Range ◽  
Neuronal Processes ◽  
Almost All

Abstract In the present study, genomic binding sites of glucocorticoid receptors (GR) were identified in vivo in the rat hippocampus applying chromatin immunoprecipitation followed by next-generation sequencing. We identified 2470 significant GR-binding sites (GBS) and were able to confirm GR binding to a random selection of these GBS covering a wide range of P values. Analysis of the genomic distribution of the significant GBS revealed a high prevalence of intragenic GBS. Gene ontology clusters involved in neuronal plasticity and other essential neuronal processes were overrepresented among the genes harboring a GBS or located in the vicinity of a GBS. Male adrenalectomized rats were challenged with increasing doses of the GR agonist corticosterone (CORT) ranging from 3 to 3000 μg/kg, resulting in clear differences in the GR-binding profile to individual GBS. Two groups of GBS could be distinguished: a low-CORT group that displayed GR binding across the full range of CORT concentrations, and a second high-CORT group that displayed significant GR binding only after administering the highest concentration of CORT. All validated GBS, in both the low-CORT and high-CORT groups, displayed mineralocorticoid receptor binding, which remained relatively constant from 30 μg/kg CORT upward. Motif analysis revealed that almost all GBS contained a glucocorticoid response element resembling the consensus motif in literature. In addition, motifs corresponding with new potential GR-interacting proteins were identified, such as zinc finger and BTB domain containing 3 (Zbtb3) and CUP (CG11181 gene product from transcript CG11181-RB), which may be involved in GR-dependent transactivation and transrepression, respectively. In conclusion, our results highlight the existence of 2 populations of GBS in the rat hippocampal genome.

scholarly journals Whole genome sequencing reveals the genomic diversity, taxonomic classification, and evolutionary relationships of the genus Nocardia

2021 ◽  
Vol 15 (8) ◽  
pp. e0009665
Author(s):  
Shuai Xu ◽  
Zhenpeng Li ◽  
Yuanming Huang ◽  
Lichao Han ◽  
Yanlin Che ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Phylogenetic Trees ◽  
Gene Families ◽  
Single Copy ◽  
Taxonomic Classification ◽  
Genomic Diversity ◽  
Evolutionary Relationships ◽  
Taxonomic Structure ◽  
Pan Genome ◽  
Dipeptidyl Aminopeptidase

Nocardia is a complex and diverse genus of aerobic actinomycetes that cause complex clinical presentations, which are difficult to diagnose due to being misunderstood. To date, the genetic diversity, evolution, and taxonomic structure of the genus Nocardia are still unclear. In this study, we investigated the pan-genome of 86 Nocardia type strains to clarify their genetic diversity. Our study revealed an open pan-genome for Nocardia containing 265,836 gene families, with about 99.7% of the pan-genome being variable. Horizontal gene transfer appears to have been an important evolutionary driver of genetic diversity shaping the Nocardia genome and may have caused historical taxonomic confusion from other taxa (primarily Rhodococcus, Skermania, Aldersonia, and Mycobacterium). Based on single-copy gene families, we established a high-accuracy phylogenomic approach for Nocardia using 229 genome sequences. Furthermore, we found 28 potentially new species and reclassified 16 strains. Finally, by comparing the topology between a phylogenomic tree and 384 phylogenetic trees (from 384 single-copy genes from the core genome), we identified a novel locus for inferring the phylogeny of this genus. The dapb1 gene, which encodes dipeptidyl aminopeptidase BI, was far superior to commonly used markers for Nocardia and yielded a topology almost identical to that of genome-based phylogeny. In conclusion, the present study provides insights into the genetic diversity, contributes a robust framework for the taxonomic classification, and elucidates the evolutionary relationships of Nocardia. This framework should facilitate the development of rapid tests for the species identification of highly variable species and has given new insight into the behavior of this genus.

scholarly journals GeneRax: A tool for species tree-aware maximum likelihood based gene family tree inference under gene duplication, transfer, and loss

2019 ◽  
Author(s):  
Benoit Morel ◽  
Alexey M. Kozlov ◽  
Alexandros Stamatakis ◽  
Gergely J. Szöllősi
Keyword(s):  
Maximum Likelihood ◽  
Phylogenetic Trees ◽  
Large Scale ◽  
Simulated Data ◽  
Gene Families ◽  
Species Tree ◽  
Homologous Gene ◽  
Sequence Alignments ◽  
Full Likelihood ◽  
True Tree

AbstractInferring phylogenetic trees for individual homologous gene families is difficult because alignments are often too short, and thus contain insufficient signal, while substitution models inevitably fail to capture the complexity of the evolutionary processes. To overcome these challenges species tree-aware methods also leverage information from a putative species tree. However, only few methods are available that implement a full likelihood framework or account for horizontal gene transfers. Furthermore, these methods often require expensive data pre-processing (e.g., computing bootstrap trees), and rely on approximations and heuristics that limit the degree of tree space exploration. Here we present GeneRax, the first maximum likelihood species tree-aware phylogenetic inference software. It simultaneously accounts for substitutions at the sequence level as well as gene level events, such as duplication, transfer, and loss relying on established maximum likelihood optimization algorithms. GeneRax can infer rooted phylogenetic trees for multiple gene families, directly from the per-gene sequence alignments and a rooted, yet undated, species tree. We show that compared to competing tools, on simulated data GeneRax infers trees that are the closest to the true tree in 90% of the simulations in terms of relative Robinson-Foulds distance. On empirical datasets, GeneRax is the fastest among all tested methods when starting from aligned sequences, and it infers trees with the highest likelihood score, based on our model. GeneRax completed tree inferences and reconciliations for 1099 Cyanobacteria families in eight minutes on 512 CPU cores. Thus, its parallelization scheme enables large-scale analyses. GeneRax is available under GNU GPL at https://github.com/BenoitMorel/GeneRax.

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