Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Class D ?-lactamases do exist in Gram-positive bacteria.

ABSTRACT: Production of ?-lactamases of one of four molecular classes (A, B, C and D) is the major mechanism of bacterial resistance to ?-lactams, the largest class of antibiotics, which have saved countless lives since their inception 70 years ago. Although several hundred efficient class D enzymes have been identified in Gram-negative pathogens over the last four decades, none have been reported in Gram-positive bacteria. Here we demonstrate that efficient class D ?-lactamases capable of hydrolyzing a wide array of ?-lactam substrates are widely disseminated in various species of environmental Gram-positive organisms. Class D enzymes of Gram-positive bacteria have a distinct structural architecture and employ a unique substrate-binding mode that is quite different from that of all currently known class A, C and D ?-lactamases. These enzymes thus constitute a previously unknown reservoir of novel antibiotic-resistance enzymes.

SUBMITTER: Toth M

PROVIDER: S-EPMC4684797 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Class D β-lactamases do exist in Gram-positive bacteria.

Toth Marta M Antunes Nuno Tiago NT Stewart Nichole K NK Frase Hilary H Bhattacharya Monolekha M Smith Clyde A CA Vakulenko Sergei B SB

Nature chemical biology 20151109 1

Production of β-lactamases of one of four molecular classes (A, B, C and D) is the major mechanism of bacterial resistance to β-lactams, the largest class of antibiotics, which have saved countless lives since their inception 70 years ago. Although several hundred efficient class D enzymes have been identified in Gram-negative pathogens over the last four decades, none have been reported in Gram-positive bacteria. Here we demonstrate that efficient class D β-lactamases capable of hydrolyzing a w ...[more]

PMID: 26551395

Similar Datasets

An unusual class of anthracyclines potentiate Gram-positive antibiotics in intrinsically resistant Gram-negative bacteria.

Project description:ObjectivesAn orthogonal approach taken towards novel antibacterial drug discovery involves the identification of small molecules that potentiate or enhance the activity of existing antibacterial agents. This study aimed to identify natural-product rifampicin adjuvants in the intrinsically resistant organism Escherichia coli.MethodsE. coli BW25113 was screened against 1120 actinomycete fermentation extracts in the presence of subinhibitory (2 mg/L) concentrations of rifampicin. The active molecule exhibiting the greatest rifampicin potentiation was isolated using activity-guided methods and identified using mass and NMR spectroscopy. Susceptibility testing and biochemical assays were used to determine the mechanism of antibiotic potentiation.ResultsThe anthracycline Antibiotic 301A(1) was isolated from the fermentation broth of a strain of Streptomyces (WAC450); the molecule was shown to be highly synergistic with rifampicin (fractional inhibitory concentration index = 0.156) and moderately synergistic with linezolid (FIC index = 0.25) in both E. coli and Acinetobacter baumannii. Activity was associated with inhibition of efflux and the synergistic phenotype was lost when tested against E. coli harbouring mutations within the rpoB gene. Structure-activity relationship studies revealed that other anthracyclines do not synergize with rifampicin and removal of the sugar moiety of Antibiotic 301A(1) abolishes activity.ConclusionsScreening only a subsection of our natural product library identified a small-molecule antibiotic adjuvant capable of sensitizing Gram-negative bacteria to antibiotics to which they are ordinarily intrinsically resistant. This result demonstrates the great potential of this approach in expanding antibiotic effectiveness in the face of the growing challenge of resistance in Gram-negatives.

| S-EPMC4054986 | biostudies-literature

Detection of AmpC β-lactamases in gram-negative bacteria.

Project description:AmpC β-lactamase genes are clinically important because they often confer resistance to most β-lactams other than 4th-generation cephalosporins and carbapenems. However, traditional and existing detection methods are expensive, labor-intensive and range-limited. We established an efficient multiplex PCR method to simultaneously identify six families of ampC β-lactamase genes, ACC, EBC, CIT, DHA, MOX and FOX, and evaluated the sensitivity and specificity of this assay. The multiplex method could accurately identify ACC, EBC, CIT, DHA, MOX and FOX variants among a total of 175 ampC β-lactamase genes. The minimum concentration of genomic DNA that could be detected was 1.0×103 copies/μL. We subsequently used this method to analyze 2 Salmonella spp. with carrying CMY-2 and DHA-1, and 167 Enterobacteriaceae isolates in blinded PCR testing. Positive isolates produced bright bands that corresponded with their genotype. Results were in concordance with those of the traditional method but showed increased sensitivity and accuracy. This indicates that the newly developed multiplex PCR system could be used as a diagnostic tool to accurately distinguish the six families of ampC β-lactamase genes with high efficiency, wide range, easy operation and good discrimination.

| S-EPMC9793173 | biostudies-literature

Sortase enzymes in Gram-positive bacteria.

Project description:In Gram-positive bacteria proteins are displayed on the cell surface using sortase enzymes. These cysteine transpeptidases join proteins bearing an appropriate sorting signal to strategically positioned amino groups on the cell surface. Working alone, or in concert with other enzymes, sortases either attach proteins to the cross-bridge peptide of the cell wall or they link proteins together to form pili. Because surface proteins play a fundamental role in microbial physiology and are frequently virulence factors, sortase enzymes have been intensely studied since their discovery a little more than a decade ago. Based on their primary sequences and functions sortases can be partitioned into distinct families called class A to F enzymes. Most bacteria elaborate their surfaces using more than one type of sortase that function non-redundantly by recognizing unique sorting signals within their protein substrates. Here we review what is known about the functions of these enzymes and the molecular basis of catalysis. Particular emphasis is placed on 'pilin' specific class C sortases that construct structurally complex pili. Exciting new data have revealed that these enzymes are amazingly promiscuous in the substrates that they can employ and that there is a startling degree of diversity in their mechanism of action. We also review recent data that suggest that sortases are targeted to specific sites on the cell surface where they work with other sortases and accessory factors to properly function.

| S-EPMC3590066 | biostudies-literature

Phage Adsorption to Gram-Positive Bacteria.

Project description:The phage life cycle is a multi-stage process initiated by the recognition and attachment of the virus to its bacterial host. This adsorption step depends on the specific interaction between bacterial structures acting as receptors and viral proteins called Receptor Binding Proteins (RBP). The adsorption process is essential as it is the first determinant of phage host range and a sine qua non condition for the subsequent conduct of the life cycle. In phages belonging to the Caudoviricetes class, the capsid is attached to a tail, which is the central player in the adsorption as it comprises the RBP and accessory proteins facilitating phage binding and cell wall penetration prior to genome injection. The nature of the viral proteins involved in host adhesion not only depends on the phage morphology (i.e., myovirus, siphovirus, or podovirus) but also the targeted host. Here, we give an overview of the adsorption process and compile the available information on the type of receptors that can be recognized and the viral proteins taking part in the process, with the primary focus on phages infecting Gram-positive bacteria.

| S-EPMC9863714 | biostudies-literature

Identification of Gram-positive bacteria using BC-GP assay

2014-05-30 | GSE57245 | GEO

Identification of Gram-positive bacteria using BC-GP assay

Project description:Signal intensities of BC-GP array for 105 speimens The Verigene Gram-Positive Blood Culture (BC-GP) nucleic acid assay is an automated microarray-based test, which can detect 12 Gram-positive bacterial genes and 3 resistance determinants using blood culture broths. We investigated signal intensities of microarray spots, and reclassified undetermined results where the automated system failed and various errors were called in blood culture specimens and spiked samples. Signal intensity analysis of BC-GP assay. SAMPLE_077 [Blood culture, Escherichia coli, Gram-negative, BacTALERT, Supernatant, Peripheral blood] had no signal data in the array raw data. Thus, SAMPLE_077 is not represented in this Series.

2014-05-30 | E-GEOD-57245 | biostudies-arrayexpress

Automated Phosphopeptide Enrichment for Gram Positive Bacteria

Project description:Protein phosphorylation in prokaryotes has gained more attention in recent years as several studies linked it to regulatory and signalling functions indicating an importance similar to protein phosphorylation in eukaryotes. Studies on bacterial phosphorylation have so far been conducted using manual or HPLC-supported phosphopeptide enrichment while automation of phosphopeptide enrichment has been established in eukaryotes, allowing for high throughput sampling. To facilitate the prospect of studying bacterial phosphorylation on a systems‐level we here establish an automated Ser/Thr/Tyr phosphopeptide enrichment workflow on the Agilent AssayMap platform. We present optimized buffer conditions for TiO2 and Fe(III)NTA-IMAC based enrichment, and the most advantageous, species specific starting amount for S. pyogenes, L. monocytogenes, and B. subtilis. Our data represents, to the best of our knowledge, the largest phosphoproteome identified by a single study for each of these bacteria. For higher sample amounts (> 250µg) we observed a superior performance of Fe(III)NTA cartridges, while more peptides were identified from smaller sample amounts using TiO2-based enrichment. Both cartridges largely enrich the same set of phosphopeptides suggesting no improvement of peptide yield from complementary use of both cartridges. Distribution of S/T/Y phosphorylation varied between bacterial strains with threonine being the main site of phosphorylation in S. pyogenes, while in B.subtilis and L. monocytogenes showed the highest percentage of phosphorylation at serine.

2021-08-26 | PXD025459 | Pride

Gram-positive bacteria are a major reservoir of Class 1 antibiotic resistance integrons in poultry litter.

Project description:Reversing the spread of antibiotic multiresistant bacteria is hampered by ignorance of the natural history of resistance genes, the mobile elements carrying them, and the bacterial hosts harboring them. Using traditional cultivation and cultivation-independent molecular techniques, we quantified antibiotic resistance genes and mobile elements called integrons in poultry house litter from commercial poultry farms. Unexpectedly, the major reservoir for Class 1 integrons in poultry litter is not their previously identified hosts, Gram-negative Enterobacteriaceae such as Escherichia coli. Rather, integrons and associated resistance genes abound in several genera of Gram-positive bacteria that constitute >85% of the litter community compared with Enterobacteriaceae that comprise <2% of this ecosystem. This finding warrants reexamination of our assumptions about the persistence and spread of antibiotic resistance genes.

| S-EPMC406475 | biostudies-literature

Genomic analysis of bifunctional Class C-Class D β-lactamases in environmental bacteria.

Project description:β-lactamases, which are found in several bacterial species and environments, are the main cause of resistance to β-lactams in Gram-negative bacteria. In 2009, a protein (LRA-13) with two β-lactamase domains (one class C domain and one class D domain) was experimentally characterised, and an extended action spectrum against β-lactams consistent with two functional domains was found. Here, we present the results of searches in the non-redundant NCBI protein database that revealed the existence of a group of homologous bifunctional β-lactamases in the genomes of environmental bacteria. These findings suggest that bifunctional β-lactamases are widespread in nature; these findings also raise concern that bifunctional β-lactamases may be transferred to bacteria of clinical importance through lateral gene transfer mechanisms.

| S-EPMC5967600 | biostudies-literature

Conjugative plasmid transfer in gram-positive bacteria.

Project description:Conjugative transfer of bacterial plasmids is the most efficient way of horizontal gene spread, and it is therefore considered one of the major reasons for the increase in the number of bacteria exhibiting multiple-antibiotic resistance. Thus, conjugation and spread of antibiotic resistance represents a severe problem in antibiotic treatment, especially of immunosuppressed patients and in intensive care units. While conjugation in gram-negative bacteria has been studied in great detail over the last decades, the transfer mechanisms of antibiotic resistance plasmids in gram-positive bacteria remained obscure. In the last few years, the entire nucleotide sequences of several large conjugative plasmids from gram-positive bacteria have been determined. Sequence analyses and data bank comparisons of their putative transfer (tra) regions have revealed significant similarities to tra regions of plasmids from gram-negative bacteria with regard to the respective DNA relaxases and their targets, the origins of transfer (oriT), and putative nucleoside triphosphatases NTP-ases with homologies to type IV secretion systems. In contrast, a single gene encoding a septal DNA translocator protein is involved in plasmid transfer between micelle-forming streptomycetes. Based on these clues, we propose the existence of two fundamentally different plasmid-mediated conjugative mechanisms in gram-positive microorganisms, namely, the mechanism taking place in unicellular gram-positive bacteria, which is functionally similar to that in gram-negative bacteria, and a second type that occurs in multicellular gram-positive bacteria, which seems to be characterized by double-stranded DNA transfer.

| S-EPMC156469 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data