scholarly journals Investigating bacterial ribosomal sequence variation in regards to future structural and antibiotic research.

2021 ◽  
Author(s):  
Helena B Cooper ◽  
Kurt L Krause ◽  
Paul P. Gardner
Keyword(s):  
Pathogenic Bacteria ◽  
Deinococcus Radiodurans ◽  
Markov Models ◽  
Genomic Sequence ◽  
Thermus Thermophilus ◽  
Campylobacter Pylori ◽  
Haloarcula Marismortui ◽  
Bacterial Ribosome ◽  
Pathogenic Escherichia Coli ◽  
Species Specific

Ribosome-targeting antibiotics comprise over half of antibiotics used in medicine, but our fundamental knowledge of their binding sites is derived primarily from ribosome structures from non-pathogenic species. These include Thermus thermophilus, Deinococcus radiodurans and Haloarcula marismortui, as well as the commensal or pathogenic Escherichia coli. Advancements in electron cryomicroscopy have allowed for the determination of more ribosome structures from pathogenic bacteria, with each study highlighting species-specific differences that had not been observed in the non-pathogenic structures. These observed differences suggest that more novel ribosome structures, particularly from pathogens, are required to get a more accurate understanding of the level of diversity in the bacterial ribosome, leading to potential advancements in antibiotic research. In this study, covariance and hidden Markov models were used to annotate ribosomal RNA and protein sequences respectively from genomic sequence, allowing us to determine the underlying ribosomal sequence diversity using phylogenetic methods. This analysis provided evidence that the current non-pathogenic ribosome structures are not sufficient representatives of some pathogenic bacteria, such as Campylobacter pylori, or of whole phyla such as Bacteroidetes.

scholarly journals Molecular Analyses of the Natural Transformation Machinery and Identification of Pilus Structures in the Extremely Thermophilic Bacterium Thermus thermophilus Strain HB27

2002 ◽  
Vol 68 (2) ◽  
pp. 745-755 ◽  
Author(s):  
Alexandra Friedrich ◽  
Christina Prust ◽  
Thomas Hartsch ◽  
Anke Henne ◽  
Beate Averhoff
Keyword(s):  
Deinococcus Radiodurans ◽  
Natural Transformation ◽  
Genomic Sequence ◽  
Thermus Thermophilus ◽  
Thermophilic Bacterium ◽  
Open Reading Frames ◽  
Gram Positive Bacteria ◽  
Type Iv ◽  
Competence Proteins ◽  
High Competence

ABSTRACT Thermus thermophilus HB27, an extremely thermophilic bacterium, exhibits high competence for natural transformation. To identify genes of the natural transformation machinery of T. thermophilus HB27, we performed homology searches in the partially completed T. thermophilus genomic sequence for conserved competence genes. These analyses resulted in the detection of 28 open reading frames (ORFs) exhibiting significant similarities to known competence proteins of gram-negative and gram-positive bacteria. Disruption of 15 selected potential competence genes led to the identification of 8 noncompetent mutants and one transformation-deficient mutant with a 100-fold reduced transformation frequency. One competence protein is similar to DprA of Haemophilus influenzae, seven are similar to type IV pilus proteins of Pseudomonas aeruginosa or Neisseria gonorrhoeae (PilM, PilN, PilO, PilQ, PilF, PilC, PilD), and another deduced protein (PilW) is similar to a protein of unknown function in Deinococcus radiodurans R1. Analysis of the piliation phenotype of T. thermophilus HB27 revealed the presence of single pilus structures on the surface of the wild-type cells, whereas the noncompetent pil mutants of Thermus, with the exception of the pilF mutant, were devoid of pilus structures. These results suggest that pili and natural transformation in T. thermophilus HB27 are functionally linked.

Acetate Kinase (AcK) is Essential for Microbial Growth and Betel-derived Compounds Potentially Target AcK, PhoP and MDR Proteins in M. tuberculosis, V. cholerae and Pathogenic E. coli: An in silico and in vitro Study

2019 ◽  
Vol 18 (31) ◽  
pp. 2731-2740 ◽  
Author(s):  
Sandeep Tiwari ◽  
Debmalya Barh ◽  
M. Imchen ◽  
Eswar Rao ◽  
Ranjith K. Kumavath ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
In Silico ◽  
Pathogenic Bacteria ◽  
In Vitro Study ◽  
Docking Studies ◽  
Acetate Kinase ◽  
E Coli ◽  
Pathogenic Escherichia Coli ◽  
Novel Target

Background: Mycobacterium tuberculosis, Vibrio cholerae, and pathogenic Escherichia coli are global concerns for public health. The emergence of multi-drug resistant (MDR) strains of these pathogens is creating additional challenges in controlling infections caused by these deadly bacteria. Recently, we reported that Acetate kinase (AcK) could be a broad-spectrum novel target in several bacteria including these pathogens. Methods: Here, using in silico and in vitro approaches we show that (i) AcK is an essential protein in pathogenic bacteria; (ii) natural compounds Chlorogenic acid and Pinoresinol from Piper betel and Piperidine derivative compound 6-oxopiperidine-3-carboxylic acid inhibit the growth of pathogenic E. coli and M. tuberculosis by targeting AcK with equal or higher efficacy than the currently used antibiotics; (iii) molecular modeling and docking studies show interactions between inhibitors and AcK that correlate with the experimental results; (iv) these compounds are highly effective even on MDR strains of these pathogens; (v) further, the compounds may also target bacterial two-component system proteins that help bacteria in expressing the genes related to drug resistance and virulence; and (vi) finally, all the tested compounds are predicted to have drug-like properties. Results and Conclusion: Suggesting that, these Piper betel derived compounds may be further tested for developing a novel class of broad-spectrum drugs against various common and MDR pathogens.

scholarly journals Usages of Salvia officinalis Boiled Water Extract for Pathogenic Escherichia coli Exclusion at Elevated Region

2021 ◽  
Vol 2 (3) ◽  
pp. 01-03
Author(s):  
Sherifa Sabra
Keyword(s):  
Escherichia Coli ◽  
Pathogenic Bacteria ◽  
Water Extract ◽  
Salvia Officinalis ◽  
Bacterial Suspension ◽  
Water Extracts ◽  
Pathogenic Escherichia Coli ◽  
Chemical Content ◽  
Boiled Water ◽  
Chemical Contents

The aim was for tryout using daily regular Salvia officinalis boiled water extracts in "Arab and Saudi Society", especially at elevated region "Taif". That to prove its ability for pathogenic Escherichia coli exclusion and had antibiotic resistance. This could prove strength of chemical content and adherence of "Arab People" to use as regular and daily to stabilize body health and protect against pathogenic bacteria. Salvia officinalis was purchased from pharmacy at "Taif" and boiled water extract was made. Pathogenic Escherichia coli was obtained from a "Licensed Health Center"; culture was made and suspensions. Tryout by boiled water extract were added to bacterial suspension and then were kept in incubator. The samples were taken at hours (1, 3, 5, 7, 9, 11, 13, 15, 17 and 19); were cultured and were kept for 48 hours at 37 °C. The exclusion percent's had determined, Escherichia coli exclusion mean percentages rose 5% at third hour and then increased 7% at fifth hour and at ninth hour was 8%. Then it decreased at the eleventh hour and thirteenth hour (2% and 3%), then rose at the fifteenth hour 10%. It decreased 5% at the seventeenth hour, and then returned and rose at the nineteenth hour 12%. It was concluded Salvia officinalis boiled water extracts effects on pathogenic Escherichia coli exclusion was found during one growth bacteria cycle, indicated the characteristics of chemical contents and good daily habit. It was recommend continuing as "Arabian Habit" Salvia officinalis boiled water extracts for health and protection stability.

scholarly journals FIND: Identifying Functionally and Structurally Important Features in Protein Sequences with Deep Neural Networks

2019 ◽  
Author(s):  
Ranjani Murali ◽  
James Hemp ◽  
Victoria Orphan ◽  
Yonatan Bisk
Keyword(s):  
Neural Networks ◽  
Amino Acid ◽  
Hidden Markov Models ◽  
Markov Models ◽  
Genomic Sequence ◽  
Hidden Markov ◽  
Amino Acid Sequences ◽  
Homologous Proteins ◽  
Biological Studies ◽  
Insight Into

AbstractThe ability to correctly predict the functional role of proteins from their amino acid sequences would significantly advance biological studies at the molecular level by improving our ability to understand the biochemical capability of biological organisms from their genomic sequence. Existing methods that are geared towards protein function prediction or annotation mostly use alignment-based approaches and probabilistic models such as Hidden-Markov Models. In this work we introduce a deep learning architecture (FunctionIdentification withNeuralDescriptions orFIND) which performs protein annotation from primary sequence. The accuracy of our methods matches state of the art techniques, such as protein classifiers based on Hidden Markov Models. Further, our approach allows for model introspection via a neural attention mechanism, which weights parts of the amino acid sequence proportionally to their relevance for functional assignment. In this way, the attention weights automatically uncover structurally and functionally relevant features of the classified protein and find novel functional motifs in previously uncharacterized proteins. While this model is applicable to any database of proteins, we chose to apply this model to superfamilies of homologous proteins, with the aim of extracting features inherent to divergent protein families within a larger superfamily. This provided insight into the functional diversification of an enzyme superfamily and its adaptation to different physiological contexts. We tested our approach on three families (nitrogenases, cytochromebd-type oxygen reductases and heme-copper oxygen reductases) and present a detailed analysis of the sequence characteristics identified in previously characterized proteins in the heme-copper oxygen reductase (HCO) superfamily. These are correlated with their catalytic relevance and evolutionary history. FIND was then applied to discover features in previously uncharacterized members of the HCO superfamily, providing insight into their unique sequence features. This modeling approach demonstrates the power of neural networks to recognize patterns in large datasets and can be utilized to discover biochemically and structurally important features in proteins from their amino acid sequences.Author summary

scholarly journals Antimicrobial Susceptibility Testing and Tentative Epidemiological Cutoff Values for FiveBacillusSpecies Relevant for Use as Animal Feed Additives or for Plant Protection

2018 ◽  
Vol 84 (19) ◽  
Author(s):  
Yvonne Agersø ◽  
Birgitte Stuer-Lauridsen ◽  
Karin Bjerre ◽  
Michelle Geervliet Jensen ◽  
Eric Johansen ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Resistance Genes ◽  
Pathogenic Bacteria ◽  
Animal Feed ◽  
Bacterial Species ◽  
Feed Additives ◽  
Content Type ◽  
Cutoff Values ◽  
Antimicrobial Resistance Genes ◽  
Species Specific

ABSTRACTBacillus megaterium(n= 29),Bacillus velezensis(n= 26),Bacillus amyloliquefaciens(n= 6),Bacillus paralicheniformis(n= 28), andBacillus licheniformis(n= 35) strains from different sources, origins, and time periods were tested for the MICs for nine antimicrobial agents by the CLSI-recommended method (Mueller-Hinton broth, 35°C, for 18 to 20 h), as well as with a modified CLSI method (Iso-Sensitest [IST] broth, 37°C [35°C forB. megaterium], 24 h). This allows a proposal of species-specific epidemiological cutoff values (ECOFFs) for the interpretation of antimicrobial resistance in these species. MICs determined by the modified CLSI method were 2- to 16-fold higher than with the CLSI-recommended method for several antimicrobials. The MIC distributions differed between species for five of the nine antimicrobials. Consequently, use of the modified CLSI method and interpretation of resistance by use of species-specific ECOFFs is recommended. The genome sequences of all strains were determined and used for screening for resistance genes against the ResFinder database and for multilocus sequence typing. A putative chloramphenicol acetyltransferase (cat) gene was found in oneB. megateriumstrain with an elevated chloramphenicol MIC compared to the otherB. megateriumstrains. InB. velezensisandB. amyloliquefaciens, a putative tetracycline efflux gene,tet(L), was found in all strains (n= 27) with reduced tetracycline susceptibility but was absent in susceptible strains. AllB. paralicheniformisand 23% ofB. licheniformisstrains had elevated MICs for erythromycin and harboredermD. The presence of these resistance genes follows taxonomy suggesting they may be intrinsic rather than horizontally acquired. Reduced susceptibility to chloramphenicol, streptomycin, and clindamycin could not be explained in all species.IMPORTANCEWhen commercializing bacterial strains, likeBacillusspp., for feed applications or plant bioprotection, it is required that the strains are free of acquired antimicrobial resistance genes that could potentially spread to pathogenic bacteria, thereby adding to the pool of resistance genes that may cause treatment failures in humans or animals. Conversely, if antimicrobial resistance is intrinsic to a bacterial species, the risk of spreading horizontally to other bacteria is considered very low. Reliable susceptibility test methods and interpretation criteria at the species level are needed to accurately assess antimicrobial resistance levels. In the present study, tentative ECOFFs for fiveBacillusspecies were determined, and the results showed that the variation in MICs followed the respective species. Moreover, putative resistance genes, which were detected by whole-genome sequencing and suggested to be intrinsic rather that acquired, could explain the resistance phenotypes in most cases.

scholarly journals Structure and function of minor pilins of type IV pili

2019 ◽  
Vol 209 (3) ◽  
pp. 301-308 ◽  
Author(s):  
Theis Jacobsen ◽  
Benjamin Bardiaux ◽  
Olivera Francetic ◽  
Nadia Izadi-Pruneyre ◽  
Michael Nilges
Keyword(s):  
Pathogenic Bacteria ◽  
Type Iv Pili ◽  
Host Cells ◽  
Type Ii Secretion ◽  
Type Iv Pilus ◽  
Type Iv ◽  
Flexible Fibers ◽  
Multiple Copies ◽  
Species Specific ◽  
And Function

AbstractType IV pili are versatile and highly flexible fibers formed on the surface of many Gram-negative and Gram-positive bacteria. Virulence and infection rate of several pathogenic bacteria, such as Neisseria meningitidis and Pseudomonas aeruginosa, are strongly dependent on the presence of pili as they facilitate the adhesion of the bacteria to the host cell. Disruption of the interactions between the pili and the host cells by targeting proteins involved in this interaction could, therefore, be a treatment strategy. A type IV pilus is primarily composed of multiple copies of protein subunits called major pilins. Additional proteins, called minor pilins, are present in lower abundance, but are essential for the assembly of the pilus or for its specific functions. One class of minor pilins is required to initiate the formation of pili, and may form a complex similar to that identified in the related type II secretion system. Other, species-specific minor pilins in the type IV pilus system have been shown to promote additional functions such as DNA binding, aggregation and adherence. Here, we will review the structure and the function of the minor pilins from type IV pili.

scholarly journals Involvement of the S-layer proteins Hpi and SlpA in the maintenance of cell envelope integrity in Deinococcus radiodurans R1

Microbiology ◽  
2006 ◽  
Vol 152 (9) ◽  
pp. 2779-2787 ◽  
Author(s):  
Heather Rothfuss ◽  
Jimmie C. Lara ◽  
Amy K. Schmid ◽  
Mary E. Lidstrom
Keyword(s):  
Stress Responses ◽  
Deinococcus Radiodurans ◽  
Cell Envelope ◽  
Thermus Thermophilus ◽  
Shear Stresses ◽  
Wild Type ◽  
Induced Stress ◽  
Backing Layer ◽  
Mutant Cells ◽  
Deinococcus Radiodurans R1

The potential functions have been investigated of two proteins in Deinococcus radiodurans R1 predicted to be involved in the maintenance and integrity of the S layer: the hexagonally packed intermediate (Hpi) protein, and SlpA (DR2577), a homologue of an S-layer SlpA protein in Thermus thermophilus. Deletion of the hpi gene had little effect on the structure of the cell envelope or on shear- or solvent-induced stress responses. However, deletion of the slpA gene caused substantial alterations in cell envelope structure, and a significant defect in resistance to solvent and shear stresses compared to the wild-type. Ultrastructural analysis of slpA mutant cells indicated loss of much of the outer Hpi protein carbohydrate coat, the ‘pink envelope’, and the membrane-like backing layer. Together these results suggest that the SlpA protein may be involved in attachment of the Hpi surface layer to the inner cell envelope, and that SlpA may play an important role in the maintenance of cell envelope integrity in D. radiodurans.

scholarly journals Genome Signature Difference between Deinococcus radiodurans and Thermus thermophilus

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Hiromi Nishida ◽  
Reina Abe ◽  
Taishi Nagayama ◽  
Kentaro Yano
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Common Ancestor ◽  
Deinococcus Radiodurans ◽  
Thermophilic Bacteria ◽  
Thermus Thermophilus ◽  
Genomic Signatures ◽  
Genome Signature ◽  
Gc Contents

The extremely radioresistant bacteria of the genus Deinococcus and the extremely thermophilic bacteria of the genus Thermus belong to a common taxonomic group. Considering the distinct living environments of Deinococcus and Thermus, different genes would have been acquired through horizontal gene transfer after their divergence from a common ancestor. Their guanine-cytosine (GC) contents are similar; however, we hypothesized that their genomic signatures would be different. Our findings indicated that the genomes of Deinococcus radiodurans and Thermus thermophilus have different tetranucleotide frequencies. This analysis showed that the genome signature of D. radiodurans is most similar to that of Pseudomonas aeruginosa, whereas the genome signature of T. thermophilus is most similar to that of Thermanaerovibrio acidaminovorans. This difference in genome signatures may be related to the different evolutionary backgrounds of the 2 genera after their divergence from a common ancestor.

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