beta-Lactamases
Microbial Sensitivity Tests
Interleukin-1beta
beta 2-Microglobulin
Receptors, Adrenergic, beta
Integrin beta3
Transforming Growth Factor beta
Integrin alpha5beta1
pKa calculations for class A beta-lactamases: influence of substrate binding. (1/5548)
Beta-Lactamases are responsible for bacterial resistance to beta-lactams and are thus of major clinical importance. However, the identity of the general base involved in their mechanism of action is still unclear. Two candidate residues, Glu166 and Lys73, have been proposed to fulfill this role. Previous studies support the proposal that Glu166 acts during the deacylation, but there is no consensus on the possible role of this residue in the acylation step. Recent experimental data and theoretical considerations indicate that Lys73 is protonated in the free beta-lactamases, showing that this residue is unlikely to act as a proton abstractor. On the other hand, it has been proposed that the pKa of Lys73 would be dramatically reduced upon substrate binding and would thus be able to act as a base. To check this hypothesis, we performed continuum electrostatic calculations for five wild-type and three beta-lactamase mutants to estimate the pKa of Lys73 in the presence of substrates, both in the Henri-Michaelis complex and in the tetrahedral intermediate. In all cases, the pKa of Lys73 was computed to be above 10, showing that it is unlikely to act as a proton abstractor, even when a beta-lactam substrate is bound in the enzyme active site. The pKa of Lys234 is also raised in the tetrahedral intermediate, thus confirming a probable role of this residue in the stabilization of the tetrahedral intermediate. The influence of the beta-lactam carboxylate on the pKa values of the active-site lysines is also discussed. (+info)Structure-function studies of Ser-289 in the class C beta-lactamase from Enterobacter cloacae P99. (2/5548)
Site-directed mutagenesis of Ser-289 of the class C beta-lactamase from Enterobacter cloacae P99 was performed to investigate the role of this residue in beta-lactam hydrolysis. This amino acid lies near the active site of the enzyme, where it can interact with the C-3 substituent of cephalosporins. Kinetic analysis of six mutant beta-lactamases with five cephalosporins showed that Ser-289 can be substituted by amino acids with nonpolar or polar uncharged side chains without altering the catalytic efficiency of the enzyme. These data suggest that Ser-289 is not essential in the binding or hydrolytic mechanism of AmpC beta-lactamase. However, replacement by Lys or Arg decreased by two- to threefold the kcat of four of the five beta-lactams tested, particularly cefoperazone, cephaloridine, and cephalothin. Three-dimensional models of the mutant beta-lactamases revealed that the length and positive charge of the side chain of Lys and Arg could create an electrostatic linkage to the C-4 carboxylic acid group of the dihydrothiazine ring of the acyl intermediate which could slow the deacylation step or hinder release of the product. (+info)Molecular and biochemical characterization of VEB-1, a novel class A extended-spectrum beta-lactamase encoded by an Escherichia coli integron gene. (3/5548)
A clinical isolate, Escherichia coli MG-1, isolated from a 4-month-old Vietnamese orphan child, produced a beta-lactamase conferring resistance to extended-spectrum cephalosporins and aztreonam. In a disk diffusion test, a typical synergistic effect between ceftazidime or aztreonam and clavulanic acid was observed along with an unusual synergy between cefoxitin and cefuroxime. The gene for VEB-1 (Vietnamese extended-spectrum beta-lactamase) was cloned and expressed in E. coli JM109. The recombinant plasmid pRLT1 produced a beta-lactamase with a pI of 5.35 and conferred high-level resistance to extended-spectrum (or oxyimino) cephalosporins and to aztreonam. Vmax values for extended-spectrum cephalosporins were uncommonly high, while the affinity of the enzyme for ceftazidime and aztreonam was relatively low. blaVEB-1 showed significant homology at the DNA level with only blaPER-1 and blaPER-2. Analysis of the deduced protein sequence showed that VEB-1 is a class A penicillinase having very low levels of homology with any other known beta-lactamases. The highest percentage of amino acid identity was 38% with PER-1 or PER-2, two uncommon class A extended-spectrum enzymes. Exploration of the genetic environment of blaVEB-1 revealed the presence of gene cassette features, i.e., (i) a 59-base element associated with blaVEB-1; (ii) a second 59-base element just upstream of blaVEB-1, likely belonging to the aacA1-orfG gene cassette; (iii) two core sites (GTTRRRY) on both sides of blaVEB-1; and (iv) a second antibiotic resistance gene 3' of blaVEB-1, aadB. blaVEB-1 may therefore be the first class A extended-spectrum beta-lactamase that is part of a gene cassette, which itself is likely to be located on a class 1 integron, as sulfamide resistance may indicate. Furthermore, blaVEB-1 is encoded on a large (> 100-kb) transferable plasmid found in a Klebsiella pneumoniae MG-2 isolated at the same time from the same patient, indicating a horizontal gene transfer. (+info)Use of an isogenic Escherichia coli panel to design tests for discrimination of beta-lactamase functional groups of Enterobacteriaceae. (4/5548)
A study was designed to determine if an isogenic panel of Escherichia coli strains containing many different beta-lactamases could be used for the preliminary screening of a large number of beta-lactam agents to identify which might be most useful in the development of a definitive test for specific beta-lactamases found among the members of family Enterobacteriaceae. The susceptibilities of 46 strains, comprising the isogenic panel, to expanded-spectrum cephalosporins, cephamycins, and aztreonam were determined in the presence and absence of beta-lactamase inhibitors in broth microdilution tests. The results indicated that strains producing extended-spectrum beta-lactamases (ESBLs) could be distinguished from strains producing other Bush-Jacoby-Medeiros functional group 2 or group 1 beta-lactamases. For strains producing group 1 beta-lactamases, cefpodoxime and ceftazidime MICs were > or = 4 micrograms/ml and addition of clavulanate did not reduce the MICs more than fourfold. For strains producing group 2 enzymes other than ESBLs, cefpodoxime and ceftazidime MICs were < or = 2 micrograms/ml. With a single exception (ceftazidime for the strain producing SHV-3), among strains producing ESBLs, cefpodoxime and ceftazidime MICs were > or = 4 micrograms/ml and addition of clavulanate reduced the MICs by more than eightfold. Cephamycins could also be used to discriminate between strains producing group 1 beta-lactamases and ESBLs, since only the former required cefotetan concentrations as high as 8 micrograms/ml or cefoxitin concentrations of > 16 micrograms/ml for inhibition. Other cephalosporins provided some discrimination between the various beta-lactamase producers, although they were not as reliable as either cefpodoxime or ceftazidime. These results indicate the utility of an isogenic panel for identification of candidate drugs among many for further testing with clinical isolates of the family Enterobacteriaceae to determine the best agents for detection of specific beta-lactamases in this family. (+info)Ketolide treatment of Haemophilus influenzae experimental pneumonia. (5/5548)
The MICs of HMR 3004 and HMR 3647 at which 90% of beta-lactamase-producing Haemophilus influenzae isolates were inhibited were 4 and 2 micrograms/ml, respectively. Both HMR 3004 and HMR 3647 were active against beta-lactamase-producing H. influenzae in a murine model of experimental pneumonia. As assessed by pulmonary clearance of H. influenzae, HMR 3004 was more effective (P < 0.05) than was azithromycin, ciprofloxacin, clarithromycin, erythromycin A, pristinamycin, or HMR 3647 in this model. (+info)Mechanisms of beta-lactam resistance amongst Pseudomonas aeruginosa isolated in an Italian survey. (6/5548)
The mechanisms of resistance to beta-lactam antibiotics in 325 isolates of Pseudomonas aeruginosa were examined. These isolates were selected because of their resistance to meropenem and imipenem (breakpoint, >4 mg/L), carbenicillin (>128 mg/L), ceftazidime (>8 mg/L), piperacillin and ticarcillin/clavulanate (>64 mg/L). The most frequent mechanism of resistance was beta-lactamase-independent, so called 'intrinsic resistance', which was found in 183 isolates and was probably due to impermeability and/or efflux mechanisms. beta-Lactamase-mediated resistance was demonstrated in 111 strains (11.1%). Derepression of Ambler Class C chromosomal beta-lactamase was detected in 64 isolates, most of which were resistant to ceftazidime and piperacillin but susceptible to meropenem, whereas secondary plasmid-encoded beta-lactamases were found in 34 isolates, all of them resistant to carboxypenicillins and ureidopenicillins and susceptible to carbapenems. Twelve strains showed more than one plasmid-encoded beta-lactamase plus derepression of chromosomal Class C enzyme. Resistance to carbapenems was independent of resistance to other beta-lactam antibiotics, indicating a different mechanism of resistance, probably due to the loss of the D2 porin. In total, 32 strains were resistant to carbapenems: 24 only to imipenem and eight to both imipenem and meropenem. (+info)Susceptibility of multidrug-resistant strains of Mycobacterium tuberculosis to amoxycillin in combination with clavulanic acid and ethambutol. (7/5548)
Thirty clinical isolates of Mycobacterium tuberculosis, 20 of which were multidrug-resistant (MDR), were tested for susceptibility to different combinations of amoxycillin, clavulanic acid and subinhibitory concentrations of ethambutol. beta-Lactamase production was assessed semiquantitatively with the nitrocefin method and susceptibility testing was performed with the BACTEC method. All isolates were beta-lactamase positive and were resistant to 16 mg/L amoxycillin. The MIC of amoxycillin in combination with clavulanic acid was > or =2 mg/L for 27/30 (90%) isolates. Addition of subinhibitory concentrations of ethambutol significantly reduced the MIC of amoxycillin for all tested isolates. Twenty-nine (97%) isolates had an MIC of amoxycillin of < or =0.5 mg/L when subinhibitory concentrations of ethambutol were added; this is well below the concentrations achievable in serum and tissue. (+info)Resistance of artificial biofilms of Pseudomonas aeruginosa to imipenem and tobramycin. (8/5548)
Viable cells of Pseudomonas aeruginosa were entrapped in alginate gel layers and incubated in a minimal glucose (15 g/L)-yeast extract (2 g/L)-salt medium to form artificial biofilm-like structures. After cultivation for 2 days, the biomass distribution inside the polymer was highly heterogeneous. The cell number reached approximately 1011 cells/g gel in the outer regions of the gel structures whereas the inner areas were less colonized (c. 10(8) cells g/gel). Killing of immobilized organisms by imipenem and tobramycin were compared with free-cell experiments (inoculum c. 10(9) cells/mL). Sessile-like bacteria displayed a higher resistance to the two antibiotics used alone or in combination than did suspended cells. Exposure for 10 h to 20 x MIC imipenem and 15 x MIC tobramycin reduced the number of viable immobilized bacteria to 0.3% and 3%, respectively, of the initial cell population, whereas these antibiotic concentrations were much more efficient (bactericidal) against free-cell cultures (5 log kill in 6 h). A synergic effect of tobramycin and imipenem was detected on bacterial suspensions but not on biofilm-like structures. Effective diffusivity measurements showed that the diffusion of imipenem in the alginate layer was not hindered. A slight but significant enhancement of beta-lactamase induction in immobilized cells as compared with their suspended counterparts was insufficient to explain the high resistance of sessile-like bacteria. (+info)Beta-lactamases are enzymes produced by certain bacteria that can break down and inactivate beta-lactam antibiotics, such as penicillins, cephalosporins, and carbapenems. This enzymatic activity makes the bacteria resistant to these antibiotics, limiting their effectiveness in treating infections caused by these organisms.
Beta-lactamases work by hydrolyzing the beta-lactam ring, a structural component of these antibiotics that is essential for their antimicrobial activity. By breaking down this ring, the enzyme renders the antibiotic ineffective against the bacterium, allowing it to continue growing and potentially causing harm.
There are different classes of beta-lactamases (e.g., Ambler Class A, B, C, and D), each with distinct characteristics and mechanisms for breaking down various beta-lactam antibiotics. The emergence and spread of bacteria producing these enzymes have contributed to the growing problem of antibiotic resistance, making it increasingly challenging to treat infections caused by these organisms.
To overcome this issue, researchers have developed beta-lactamase inhibitors, which are drugs that can bind to and inhibit the activity of these enzymes, thus restoring the effectiveness of certain beta-lactam antibiotics. Examples of such combinations include amoxicillin/clavulanate (Augmentin) and piperacillin/tazobactam (Zosyn).
Cephaloridine is a type of antibiotic that belongs to the class of cephalosporins. It is used for treating various bacterial infections, including respiratory tract infections, urinary tract infections, skin and soft tissue infections, bone and joint infections, and septicemia.
Cephaloridine works by inhibiting the synthesis of the bacterial cell wall, leading to bacterial death. It is administered intramuscularly or intravenously and is known for its broad-spectrum activity against both Gram-positive and Gram-negative bacteria. However, due to its potential nephrotoxicity (kidney toxicity), it has largely been replaced by other antibiotics with similar spectra of activity but better safety profiles.
It's important to note that the use of cephaloridine should be reserved for infections caused by bacteria that are resistant to other antibiotics, and its administration should be closely monitored by a healthcare professional to minimize the risk of adverse effects.
Microbial sensitivity tests, also known as antibiotic susceptibility tests (ASTs) or bacterial susceptibility tests, are laboratory procedures used to determine the effectiveness of various antimicrobial agents against specific microorganisms isolated from a patient's infection. These tests help healthcare providers identify which antibiotics will be most effective in treating an infection and which ones should be avoided due to resistance. The results of these tests can guide appropriate antibiotic therapy, minimize the potential for antibiotic resistance, improve clinical outcomes, and reduce unnecessary side effects or toxicity from ineffective antimicrobials.
There are several methods for performing microbial sensitivity tests, including:
1. Disk diffusion method (Kirby-Bauer test): A standardized paper disk containing a predetermined amount of an antibiotic is placed on an agar plate that has been inoculated with the isolated microorganism. After incubation, the zone of inhibition around the disk is measured to determine the susceptibility or resistance of the organism to that particular antibiotic.
2. Broth dilution method: A series of tubes or wells containing decreasing concentrations of an antimicrobial agent are inoculated with a standardized microbial suspension. After incubation, the minimum inhibitory concentration (MIC) is determined by observing the lowest concentration of the antibiotic that prevents visible growth of the organism.
3. Automated systems: These use sophisticated technology to perform both disk diffusion and broth dilution methods automatically, providing rapid and accurate results for a wide range of microorganisms and antimicrobial agents.
The interpretation of microbial sensitivity test results should be done cautiously, considering factors such as the site of infection, pharmacokinetics and pharmacodynamics of the antibiotic, potential toxicity, and local resistance patterns. Regular monitoring of susceptibility patterns and ongoing antimicrobial stewardship programs are essential to ensure optimal use of these tests and to minimize the development of antibiotic resistance.
Anti-bacterial agents, also known as antibiotics, are a type of medication used to treat infections caused by bacteria. These agents work by either killing the bacteria or inhibiting their growth and reproduction. There are several different classes of anti-bacterial agents, including penicillins, cephalosporins, fluoroquinolones, macrolides, and tetracyclines, among others. Each class of antibiotic has a specific mechanism of action and is used to treat certain types of bacterial infections. It's important to note that anti-bacterial agents are not effective against viral infections, such as the common cold or flu. Misuse and overuse of antibiotics can lead to antibiotic resistance, which is a significant global health concern.
Interleukin-1 beta (IL-1β) is a member of the interleukin-1 cytokine family and is primarily produced by activated macrophages in response to inflammatory stimuli. It is a crucial mediator of the innate immune response and plays a key role in the regulation of various biological processes, including cell proliferation, differentiation, and apoptosis. IL-1β is involved in the pathogenesis of several inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, and atherosclerosis. It exerts its effects by binding to the interleukin-1 receptor, which triggers a signaling cascade that leads to the activation of various transcription factors and the expression of target genes.
Beta-2 microglobulin (β2M) is a small protein that is a component of the major histocompatibility complex class I molecule, which plays a crucial role in the immune system. It is found on the surface of almost all nucleated cells in the body and is involved in presenting intracellular peptides to T-cells for immune surveillance.
β2M is produced at a relatively constant rate by cells throughout the body and is freely filtered by the glomeruli in the kidneys. Under normal circumstances, most of the filtrated β2M is reabsorbed and catabolized in the proximal tubules of the nephrons. However, when the glomerular filtration rate (GFR) is decreased, as in chronic kidney disease (CKD), the reabsorption capacity of the proximal tubules becomes overwhelmed, leading to increased levels of β2M in the blood and its subsequent appearance in the urine.
Elevated serum and urinary β2M levels have been associated with various clinical conditions, such as CKD, multiple myeloma, autoimmune disorders, and certain infectious diseases. Measuring β2M concentrations can provide valuable information for diagnostic, prognostic, and monitoring purposes in these contexts.
Adrenergic receptors are a type of G protein-coupled receptor that binds and responds to catecholamines, such as epinephrine (adrenaline) and norepinephrine (noradrenaline). Beta adrenergic receptors (β-adrenergic receptors) are a subtype of adrenergic receptors that include three distinct subclasses: β1, β2, and β3. These receptors are widely distributed throughout the body and play important roles in various physiological functions, including cardiovascular regulation, bronchodilation, lipolysis, and glucose metabolism.
β1-adrenergic receptors are primarily located in the heart and regulate cardiac contractility, chronotropy (heart rate), and relaxation. β2-adrenergic receptors are found in various tissues, including the lungs, vascular smooth muscle, liver, and skeletal muscle. They mediate bronchodilation, vasodilation, glycogenolysis, and lipolysis. β3-adrenergic receptors are mainly expressed in adipose tissue, where they stimulate lipolysis and thermogenesis.
Agonists of β-adrenergic receptors include catecholamines like epinephrine and norepinephrine, as well as synthetic drugs such as dobutamine (a β1-selective agonist) and albuterol (a non-selective β2-agonist). Antagonists of β-adrenergic receptors are commonly used in the treatment of various conditions, including hypertension, angina pectoris, heart failure, and asthma. Examples of β-blockers include metoprolol (a β1-selective antagonist) and carvedilol (a non-selective β-blocker with additional α1-adrenergic receptor blocking activity).
Integrin β3 is a subunit of certain integrin heterodimers, which are transmembrane receptors that mediate cell-cell and cell-extracellular matrix (ECM) adhesion. Integrin β3 combines with either integrin αv (to form the integrin αvβ3) or integrin αIIb (to form the integrin αIIbβ3). These integrins are involved in various cellular processes, including platelet aggregation, angiogenesis, and tumor metastasis.
Integrin αIIbβ3 is primarily expressed on platelets and mediates platelet aggregation by binding to fibrinogen, von Willebrand factor, and other adhesive proteins in the ECM. Integrin αvβ3 is widely expressed in various cell types and participates in diverse functions such as cell migration, proliferation, differentiation, and survival. It binds to a variety of ECM proteins, including fibronectin, vitronectin, and osteopontin, as well as to soluble ligands like vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β).
Dysregulation of integrin β3 has been implicated in several pathological conditions, such as thrombosis, atherosclerosis, tumor metastasis, and inflammatory diseases.
Transforming Growth Factor-beta (TGF-β) is a type of cytokine, which is a cell signaling protein involved in the regulation of various cellular processes, including cell growth, differentiation, and apoptosis (programmed cell death). TGF-β plays a critical role in embryonic development, tissue homeostasis, and wound healing. It also has been implicated in several pathological conditions such as fibrosis, cancer, and autoimmune diseases.
TGF-β exists in multiple isoforms (TGF-β1, TGF-β2, and TGF-β3) that are produced by many different cell types, including immune cells, epithelial cells, and fibroblasts. The protein is synthesized as a precursor molecule, which is cleaved to release the active TGF-β peptide. Once activated, TGF-β binds to its receptors on the cell surface, leading to the activation of intracellular signaling pathways that regulate gene expression and cell behavior.
In summary, Transforming Growth Factor-beta (TGF-β) is a multifunctional cytokine involved in various cellular processes, including cell growth, differentiation, apoptosis, embryonic development, tissue homeostasis, and wound healing. It has been implicated in several pathological conditions such as fibrosis, cancer, and autoimmune diseases.
Integrin α5β1, also known as very late antigen-5 (VLA-5) or fibronectin receptor, is a heterodimeric transmembrane receptor protein composed of two subunits: α5 and β1. This integrin is widely expressed in various cell types, including endothelial cells, smooth muscle cells, and fibroblasts.
Integrin α5β1 plays a crucial role in mediating cell-matrix adhesion by binding to the arginine-glycine-aspartic acid (RGD) sequence present in the extracellular matrix protein fibronectin. The interaction between integrin α5β1 and fibronectin is essential for various biological processes, such as cell migration, proliferation, differentiation, and survival. Additionally, this integrin has been implicated in several pathological conditions, including tumor progression, angiogenesis, and fibrosis.
Integrin beta4, also known as ITGB4 or CD104, is a type of integrin subunit that forms part of the integrin receptor along with an alpha subunit. Integrins are transmembrane proteins involved in cell-cell and cell-extracellular matrix (ECM) adhesion, signal transduction, and regulation of various cellular processes such as proliferation, differentiation, and migration.
Integrin beta4 is unique among the integrin subunits because it has a large cytoplasmic domain that can interact with several intracellular signaling molecules, making it an important regulator of cell behavior. Integrin beta4 is widely expressed in various tissues, including epithelial cells, endothelial cells, and hematopoietic cells.
Integrin beta4 forms heterodimers with integrin alpha6 to form the receptor for laminins, which are major components of the basement membrane. This receptor is involved in maintaining the integrity of epithelial tissues and regulating cell migration during development, tissue repair, and cancer progression. Mutations in ITGB4 have been associated with several human diseases, including epidermolysis bullosa, a group of inherited skin disorders characterized by fragile skin and blistering.
Beta-lactamase
Beta-Lactamase Database
Beta-Lactamase Database (BLDB)
Beta-Lactamase Database (BLAD)
Beta-lactamase inhibitor protein
Metallo-beta-lactamase protein fold
New Delhi metallo-beta-lactamase 1
Mariana Castanheira
Vaborbactam
CBMAR
Pathogenic Escherichia coli
Ureidopenicillin
Discovery and development of cephalosporins
Doripenem
Klebsiella pneumoniae
Raoultella
Stanley Falkow
Cefoxitin
LACTB2
LACTB
Β-Lactamase inhibitor
SCHEMA (bioinformatics)
Tazobactam
DD-transpeptidase
Antibiotic
Cefalexin
Ampicillin
Carboxypenicillin
Cefquinome
Karen Bush
Catalytic triad
Beta-lactamase - Wikipedia
New Delhi metallo-beta-lactamase 1 - Wikipedia
Detection of Enterobacteriaceae Isolates Carrying Metallo-Beta-Lactamase --- United States, 2010
Novel method for detection of beta-lactamases by using a chromogenic cephalosporin substrate
3G35: CTX-M-9 class A beta-lactamase complexed with compound 12 (F13)
AID 1085423 - Inhibition of beta-lactamase SHV-61 - PubChem
Antibiotic Resistant Bacteria including: MRSA, Beta-lactamases - FluTrackers News and Information
Caracterização de betalactamases de espectro ampliado e KPC em Enterobacter cloacae...
British Library EThOS: Molecular characterisation of the OXA-2 beta-lactamase
Chain A, Beta-lactamase (Aeromonas hydrophila) | Protein Target - PubChem
SCOP 1.75: Fold e.3: beta-lactamase/transpeptidase-like
Molecular characterization of CTX-M type Extended Spectrum Beta Lactamase producing E. coli isolated from humans and the...
SciELO - Brazil - Serogroup identification, phenotypic detection of hemolysis and extended spectrum beta-lactamases of...
Clinico epidemiologic and molecular characterization of metallo beta lactamases (MBLs) producing nosocomial Pseudomonas...
Beta-lactam and Beta-lactamase Inhibitors Market Like to Hit $34,170 Million by 2028 - PharmiWeb.com
Frequency of disinfectant resistance genes and genetic linkage with beta-lactamase transposon Tn552 among clinical...
SciELO - Brazil - Horizontol dissemination of TEM- and SHV-typr beta-lactamase genes-carrying resistance plasmids amongst...
Medical Science Monitor | A step towards the discrimination of beta-lactamase-producing clinical isolates of Enterobacteriaceae...
Use of Intralactam for the early detection of staphylococcal beta-lactamase. | Journal of Clinical Pathology
Purification and characterization of a beta-lactamase from Haemophilus ducreyi in Escherichia coli | Lund University...
Antibiotic resistance patterns and beta-lactamase identification in Escherichia coli isolated from young children in rural...
BETA LACTAMASE STICKS - Launch Diagnostics
beta-Lactamases- the Threat Renews<...
Generic Medicines Under Beta-Lactamase Inhibitors Category | Medicine India
RCSB PDB - 4F6Z: Mutagenesis of zinc ligand residue Cys221 reveals plasticity in the IMP-1 metallo-b-lactamase active site
Functional Characterization of Putative Beta-Lactamases in Pseudomonas aeruginosa
Antibiotics | Free Full-Text | In Vitro Activity of Essential Oils Against Planktonic and Biofilm Cells of Extended-Spectrum β...
Beta-Lactamase DataBase (BLDB): Structure and Function
Extended-Spectrum Beta-Lactamase | Healthcare Essay Example
ESBL10
- The infections caused by the Extended Spectrum Beta Lactamase (ESBL) enzymes-producing E. coli hinder antibiotic treatment. (nih.gov)
- In addition, hemolysis and production of Extended Spectrum Beta-Lactamases (ESBL) was assessed in the isolates. (scielo.br)
- As adequate and rapid screening methods for antibiotic resistance are crucially needed, the present study investigated the discrimination potential of MALDI-TOF MS among extended-spectrum-beta-lactamase (ESBL) or metallo-beta-lactamases- (MBL) producing and the nonproducing strains of Escherichia coli (n=19), Klebsiella pneumoniae (n=19), and Pseudomonas aeruginosa (n=38), respectively. (medscimonit.com)
- The extended-spectrum β-lactamase (ESBL)-producing bacteria have been isolated at increasing frequency worldwide. (scielo.br)
- O isolamento de bactérias produtoras de beta-lactamases de espectro expandido (ESBL) está aumentando no mundo todo. (scielo.br)
- First of all, it concerns pathogens producing expanded spectrum β-lactamases, ESBL. (assignology.com)
- Applying broiler litter containing extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) to arable land poses a potential risk for humans to get colonized by contact with contaminated soil or vegetables. (fu-berlin.de)
- In the current study prevalence and characterization of extended spectrum beta-lactamase(ESBL) production of Escherichia coli was detected from broilers of West Bengal, India. (ijcmas.com)
- Extended spectrum beta-lactamase (ESBL) producing Escherichia coli has been an emerging etiologic agent in the community acquired infections. (omu.edu.tr)
- Extended-spectrum beta-lactamase (ESBL) and AmpC enzymes are important AMR mechanisms that erode the efficacy of important antibiotics. (eijppr.com)
Escherichia3
- A pCb plasmid encoding a beta-lactamase from Haemophilus ducreyi was transferred to Escherichia coli, purified, and characterized. (lu.se)
- Despite the recent global spread of CTX-M β-lactamases in Escherichia coli isolates from community-acquired urinary tract infections (CA-UTIs), their dissemination has been little studied in developing countries. (cdc.gov)
- Plasmid-encoded AmpC expression is also constitutive and may be spread among bacteria usually lacking this beta-lactamase, such as Escherichia coli , Klebsiella pneumoniae , and Proteus mirabilis . (merckmanuals.com)
Inhibitors13
- Chromosomal-mediated AmpC β-lactamases represent a new threat, since they confer resistance to 7-alpha-methoxy-cephalosporins (cephamycins) such as cefoxitin or cefotetan but are not affected by commercially available β-lactamase inhibitors, and can, in strains with loss of outer membrane porins, provide resistance to carbapenems. (wikipedia.org)
- Beta-lactam and Beta-lactamase Inhibitors Market Like to. (pharmiweb.com)
- Pune, Maharashtra, India, February 22 2021 (Wiredrelease) Allied Analytics -:Beta-lactam and beta-lactamase inhibitors are chemical compounds of natural or semi-synthetic or synthetic origin. (pharmiweb.com)
- The beta-lactam and beta-lactamase inhibitors market is expected to exhibit significant growth during the forecast period due to increased consumption in low and middle-income countries (LMICs) and rise in prevalence of infectious diseases. (pharmiweb.com)
- In addition, development of novel approaches for new beta-lactam and beta-lactamase inhibitors for treating bacterial infections and a large number of clinical trials, further supplement the market growth. (pharmiweb.com)
- The cephalosporin segment accounted more than two-fifths of the total beta-lactam and beta-lactamase inhibitors market share in 2018. (pharmiweb.com)
- However, development of antibiotic resistance, driven by misuse of beta-lactam and beta-lactamase inhibitors and the time taken for the regulatory approval is projected to impede the market growth. (pharmiweb.com)
- Combination segment is further categorized into penicillin/beta lactamase inhibitors, cephalosporins/beta lactamase inhibitors, and carbapenems/beta lactamase inhibitors. (pharmiweb.com)
- Asia-Pacific was the leading revenue contributor to the global beta-lactam and beta-lactamase inhibitors market in 2018, and is expected to remain dominant throughout the forecast period. (pharmiweb.com)
- The report provides a comprehensive analysis of the key players operating in the global beta-lactam and beta-lactamase inhibitors market industry, namely, Abbott Laboratories, Allergan Plc. (pharmiweb.com)
- U.S. generated the highest revenue in the global beta-lactam and beta-lactamase inhibitors in 2018, accounting more than one-fifth of the global market in 2018. (pharmiweb.com)
- Tony Fink's work contributed greatly to our understanding of the mechanisms and active site function of beta-lactamases and this knowledge now informs the search for new beta-lactams and beta-lactamase inhibitors. (uea.ac.uk)
- These enzymes are not inhibited by currently available beta-lactamase inhibitors. (merckmanuals.com)
Metallo beta lactamases2
- Serine β-lactamases are grouped by sequence similarity into types A, C, and D. The other type of beta-lactamase is of the metallo type ("type B"). Metallo-beta-lactamases (MBLs) need metal ion(s) (1 or 2 Zn2+ ions) on their active site for their catalytic activities. (wikipedia.org)
- Classes A, C, and D have a serine residue at the active site, whereas class B enzymes have zinc at the active site, ie, metallo-beta-lactamases (MBLs). (merckmanuals.com)
Spectrum beta lactamases3
- P. mirabilis) due to the production of TEM- or SHV-type ESBLs (extended spectrum beta lactamases). (wikipedia.org)
- The main mechanisms of resistance to these antimicrobial classes are the production of extended spectrum beta-lactamases and carbapenemases. (usp.br)
- Thus, penicillin G was undermined by swift accumulation of staphylococcal penicillinase, ampicillin by TEM-1 enzyme and modern oxymino cephalosporins by "extended-spectrum" beta-lactamases. (uea.ac.uk)
Extended-spectrum6
- In the mid-1980s, this new group of enzymes, the extended-spectrum β-lactamases (ESBLs), was detected (first detected in 1979). (wikipedia.org)
- ESBLs are beta-lactamases that hydrolyze extended-spectrum cephalosporins with an oxyimino side chain. (wikipedia.org)
- In a 2-year prospective study, we documented the prevalence of extended-spectrum β-lactamases (ESBLs) in E. coli that were responsible for CA-UTIs in Phnom-Penh, Cambodia. (cdc.gov)
- TEM-1, TEM-2, and SHV-1) and extended-spectrum β-lactamases (ESBLs) (e.g. (cdc.gov)
- E.coli isolates were serotyped and also screened for extended spectrum beta-lactamase by double disc diffusion assay and by PCR detection of bla CTX-M, bla SHV, and bla TEM genes. (ijcmas.com)
- CTX-M Type Extended Spectrum beta-Lactam. (omu.edu.tr)
ENTEROBACTERIACEAE3
- During January--June 2010, three Enterobacteriaceae isolates carrying a newly described resistance mechanism, the New Delhi metallo-beta-lactamase (NDM-1) ( 1 ), were identified from three U.S. states at the CDC antimicrobial susceptibility laboratory. (cdc.gov)
- This is the first report of NDM-1 in the United States, and the first report of metallo-beta-lactamase carriage among Enterobacteriaceae in the United States. (cdc.gov)
- A new cephalosporin with a highly reactive beta-lactam ring was found to give an immediate color change in the presence of beta-lactamases from many bacteria, including staphylococci, Bacillus species, Enterobacteriaceae, and Pseudomonas. (nih.gov)
Pseudomonas2
- Background and Objective: Metallo-beta-lactamase (MBL)-mediated resistance is an emerging threat in hospital isolates of Pseudomonas aeruginosa . (iranpath.org)
- Phenotypic Detection Of Metallo-beta-lactamase Producing Pseudomonas aeruginosa Strains Isolated From Burned Patients', Iranian Journal of Pathology , 3(1), pp. 20-25. (iranpath.org)
Cephalosporins5
- Beta-lactamases (β-lactamases) are enzymes (EC 3.5.2.6) produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems (ertapenem), although carbapenems are relatively resistant to beta-lactamase. (wikipedia.org)
- INTRODUCTION: The treatment of healthcare associated infections caused by enterobacteria represents a growing challenge due to the increasing prevalence of beta-lactam resistance, particularly to third and fourth generations cephalosporins and carbapenems. (usp.br)
- Amino acid sequencing of some beta-lactamases has shown that substitution of only a few amino acids in the bla gene leads to high-level resistance against specific cephalosporins. (lu.se)
- OXA beta-lactamases primarily hydrolyze narrow spectrum penicillins but certain OXA variants such as the plasmid encoded OXA 48 can hydrolyze carbapenems, even while leaving many cephalosporins active. (merckmanuals.com)
- Resistance develops much less frequently with fourth-generation cephalosporins because they are relatively stable to AmpC beta-lactamase but not (so far) to the less frequently encountered ESBLs (see Medical Care). (medscape.com)
Isolates3
- Metallo-- lactamase (MBL) producing carbapenem resistant clinical isolates are an increasingly difficult problem in health care settings because of the treatment difficulties and rapid spread of these infections. (researchbib.com)
- The present study aims in detecting the MBL production among carbapenem resistant clinical isolates.54 non repetitive clinical isolates of carbapenem resistant gram negative bacteria were studied to detect the Metallo-- lactamase production. (researchbib.com)
- Carbapenemases are a class of enzymes that can confer resistance to carbapenems and other Beta-lactam antibiotic drugs, but not all carbapenemase-producing isolates are carbapenem-resistant. (cdc.gov)
Resistance13
- Beta-lactamase provides antibiotic resistance by breaking the antibiotics' structure. (wikipedia.org)
- Penicillinase-resistant beta-lactams such as methicillin were developed, but there is now widespread resistance to even these. (wikipedia.org)
- Thus ESBLs confer multi-resistance to these antibiotics and related oxyimino-beta lactams. (wikipedia.org)
- The carbapenems were developed to overcome antibiotic resistance mediated by bacterial beta-lactamase enzymes. (wikipedia.org)
- Another probe which comprised the whole of the OXA-2 beta-lactamase gene as well as segments of DNA on either side of the gene, was found to hybridise with a number of resistance plasmids. (bl.uk)
- It confirmed that the enzyme belonged to a class A beta-lactamase which had 99% identity to the ampicillin resistance transposon Tn3 of pBR322. (lu.se)
- Beta-lactamases are the greatest single source of resistance to beta-lactam antibiotics. (uea.ac.uk)
- For over 60 years, clinicians have seen a pattern whereby useful new beta-lactam analogues are introduced but then select for new beta-lactamases that cause resistance. (uea.ac.uk)
- Metallo-β-lactamases catalyze the hydrolysis of a broad range of β-lactam antibiotics and are a concern for the spread of drug resistance. (rcsb.org)
- These results show that PA2915 and PA0832 possess low level β-lactamase activity but do not provide any significant resistance against β-lactam antibiotics in P. aeruginosa. (uoguelph.ca)
- β-lactam resistance is mostly mediated through acquisition of β-lactamase genes located on mobile genetic elements such as plasmids or transposons. (cdc.gov)
- Beta-lactamase production is among the most clinically important mechanisms of resistance for gram-negative bacterial pathogens. (merckmanuals.com)
- In this study, we showed that the presence of the New Delhi metallo-β-lactamase (NDM) facilitates the emergence of resistance via nonsynonymous mutations of the CirA catecholate siderophore receptor. (uni-luebeck.de)
Characterization1
- Characterization of a new metallo-β-lactamase gene, bla NDM-1 , and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. (cdc.gov)
Types of beta-lactamases2
- The two types of beta-lactamases work on the basis of the two basic mechanisms of opening the β-lactam ring. (wikipedia.org)
- Understanding the most common types of beta-lactamases produced by different pathogens can help with susceptibility interpretation, therapeutic decision making, and infection control practices. (merckmanuals.com)
Enzymes5
- The gene for NDM-1 is one member of a large gene family that encodes beta-lactamase enzymes called carbapenemases. (wikipedia.org)
- A more detailed analysis has revealed from comparison of both primary and predicted secondary structure, that the OXA-2 beta-lactamase may be more closely related to class A enzymes. (bl.uk)
- P. aeruginosa also produces numerous antibiotic-inactivating enzymes such as β-lactamases, which target and break down β-lactam antibiotics. (uoguelph.ca)
- All beta-lactams bind to and inactivate enzymes required for bacterial cell wall synthesis. (merckmanuals.com)
- Beta-lactamases are a diverse class of enzymes produced by bacteria that break open the beta-lactam ring, inactivating the beta-lactam antibiotic. (merckmanuals.com)
ESBLs1
- Until recently, most ESBLs in clinical samples came from a hospital environment, belonged to the TEM or SHV β-lactamase family, and were produced by Klebsiella spp. (cdc.gov)
Enzyme11
- Through hydrolysis, the enzyme lactamase breaks the β-lactam ring open, deactivating the molecule's antibacterial properties. (wikipedia.org)
- The alpha-beta fold (InterPro: IPR012338) resembles that of a DD-transpeptidase, from which the enzyme is thought to have evolved from. (wikipedia.org)
- NDM-1 is an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotics. (wikipedia.org)
- However, the blaNDM-1 gene produces NDM-1, which is a carbapenemase beta-lactamase - an enzyme that hydrolyzes and inactivates these carbapenem antibiotics. (wikipedia.org)
- The reaction is confined to organisms producing beta-lactamases, but it is sufficiently sensitive to indicate the presence of this enzyme is small amounts in strains previously considered not to produce it. (nih.gov)
- Confirmation that the OXA-2 beta-lactamase is a serine enzyme has come from the DNA sequence and the interaction with mechanism based inactivators. (bl.uk)
- Characterisation of the physical properties of the OXA-2 enzyme by analytical ultracentrifugation have not only confirmed the dimeric nature of this beta-lactamase but have also shown that this enzyme forms aggregates at high protein concentrations. (bl.uk)
- Probing of the enzyme structure with trypsin, strongly points to the OXA-2 beta-lactamase having a domain structure. (bl.uk)
- Nevertheless, it should be recognized that the first β-lactamase enzyme produced by a Gram negative pathogen was discovered back in 1960 in Greece (Munoz-Price, 2019). (assignology.com)
- Jacobs-Wagner's career started off with a bang when, as a graduate student at the University of Liège in the early 1990s, she discovered that some bacteria can induce the enzyme beta-lactamase when exposed to antibiotics such cephalosporin, rendering them resistant to these drugs. (the-scientist.com)
- Working with experts in protein chemistry, genetics, beta-lactamase biochemistry, cell wall synthesis, and medical microbiology - in Belgium, France, the United States, and Sweden - Jacobs-Wagner discovered a regulatory protein that can sense the peptidoglycans that accumulate when antibiotics disrupt cell wall synthesis, and then activate transcription of beta-lactamase, the enzyme that disarms the drugs. (the-scientist.com)
Klebsiella1
- Among the known carbapenemases are Klebsiella pneumoniae carbapenemase, or KPC, and Verona integrin-encoded metallo-Beta-lactamase, or VIM. (cdc.gov)
Penicillin2
- The beta-lactamase could hydrolyze both penicillin antibiotics including ampicillin, benzylpenicillin, and carbenicillin as well as cephalosporin antibiotics including nitrocefin, cephalothin, cephaloridine, and cefoperazone. (lu.se)
- Antipseudomonal penicillin plus beta-lactamase inhibitor that provides coverage against most gram-positive organisms, most gram-negative organisms, and most anaerobes. (medscape.com)
Antibiotics6
- These antibiotics all have a common element in their molecular structure: a four-atom ring known as a beta-lactam (β-lactam) ring. (wikipedia.org)
- Beta-lactam antibiotics are typically used to target a broad spectrum of gram-positive and gram-negative bacteria. (wikipedia.org)
- Beta-lactamases produced by gram-negative bacteria are usually secreted, especially when antibiotics are present in the environment. (wikipedia.org)
- Carbapenems are a class of beta-lactam antibiotics that are capable of killing most bacteria by inhibiting the synthesis of one of their cell wall layers. (wikipedia.org)
- Beta-lactams are antibiotics that have a beta-lactam ring nucleus. (merckmanuals.com)
- Drug combination treats bacteria resistant to beta-lactam antibiotics. (medscape.com)
Strains1
- All strains now produce beta-lactamase. (msdmanuals.com)
Delhi1
- The structure of the New Delhi metallo-beta-lactamase 1 is given by 6C89. (wikipedia.org)
Zinc1
- citation needed] NDM-1 functions through two zinc ions present in the active site that cause hydrolysis of the beta-lactams, rendering them ineffective. (wikipedia.org)
Detection2
- Use of Intralactam for the early detection of staphylococcal beta-lactamase. (bmj.com)
- This rapid test is used for detection of Beta-lactamase in milk based on the colloidal gold immunochromatography technology. (bioeasy.com)
AmpC1
- AmpC beta-lactamase may be chromosome- or plasmid-encoded. (merckmanuals.com)
Produced by bacteria1
- They are more active against lactamases produced by bacteria. (howmed.net)
Inhibitor2
- Clavulanic acid and a novel beta-lactamase inhibitor, BRL36148, both interact specifically with the OXA-2 beta-lactamase by branched pathway mechanisms. (bl.uk)
- Drug combination of beta-lactamase inhibitor with ampicillin. (medscape.com)
Sequence3
Protein1
- Livermore, DM 2009, ' beta-Lactamases- the Threat Renews ', Current Protein and Peptide Science , vol. 10, no. 5, pp. 397-400. (uea.ac.uk)
Penicillins1
- Penicillinase is a specific type of β-lactamase, showing specificity for penicillins, again by hydrolysing the β-lactam ring. (wikipedia.org)
Carbapenemase2
- other types of carbapenemase are class A or class D beta-lactamases. (wikipedia.org)
- X-ray analysis of the NMC-A beta-lactamase at 1.64-A resolution, a class A carbapenemase with broad substrate specificity. (expasy.org)
Serine1
- The structure of a Streptomyces serine β-lactamase (SBLs) is given by 1BSG. (wikipedia.org)
Molecular1
- It groups beta-lactamases by class on the basis of molecular homology. (merckmanuals.com)
Prevalence1
- The prevalence of CTX-M β-lactamases has reached a critical level in Cambodia, which highlights the need for study of their spread in developing countries. (cdc.gov)
Gene1
- We used a cell-based human FXR β-lactamase ( Bla ) reporter gene assay to profile the Tox21 10K compound collection of environmental chemicals and drugs. (nature.com)
Inhibition1
- Inhibition of metallo-β-lactamase activity using dipicolinic acid prevented the emergence of cefiderocol-resistant mutants successfully. (uni-luebeck.de)
Infections caused1
- This finding implies that caution should be taken when using cefiderocol for the treatment of infections caused by metallo-β-lactamase-producing bacteria. (uni-luebeck.de)
Carbapenemases1
- Os mecanismos de resistência mais relevantes a essas classes de antimicrobianos, em enterobactérias, é a produção de betalactamases de espectro ampliado e carbapenemases. (usp.br)
Chromogenic1
- In addition, the target proteins were biochemically characterized in vitro by detecting β-lactamase activity using the standard chromogenic β-lactam substrate, nitrocefin. (uoguelph.ca)
Enterobacterales1
- Nonetheless, the emergence of cefiderocol in metallo-β-lactamase-producing Enterobacterales during therapy has been reported on more than one occasion. (uni-luebeck.de)
Enterobacter1
- Caracterização de betalactamases de espectro ampliado e KPC em Enterobacter cloacae. (usp.br)
Coli1
- Most β-lactamases found in E. coli belong to Ambler class A and can be further divided into narrow-spectrum β-lactamases (e.g. (cdc.gov)
Class2
- It appeared initially in a limited number of bacterial species (E. cloacae, C. freundii, S. marcescens, and P. aeruginosa) that could mutate to hyperproduce their chromosomal class C β-lactamase. (wikipedia.org)
- no good homologies were observed with any class of beta-lactamase. (bl.uk)
Fold1
- [5] [6] The propeptide region has an open-sandwich antiparallel-alpha/antiparallel-beta fold, with two alpha-helices and four beta-strands with a (beta/alpha/beta)x2 topology. (wikipedia.org)
Species1
- Material/Methods: We used a MALDI-TOF MS protocol, usually applied for species identification, in order to integrate a screening method for beta-lactamases into the routine species identification workflow. (medscimonit.com)
Genetic1
- Genetic homogeneity among beta-lactamases is remarkable. (lu.se)
Clinically1
- Drugs having beta lactam molecules are not clinically given alone. (howmed.net)