scholarly journals Des-, syn- and anti-oxyimino-Δ3-cephalosporins. Intrinsic reactivity and reaction with RTEM-2 serine β-lactamase and d-alanyl-d-alanine-cleaving serine and Zn2+-containing peptidases

1984 ◽  
Vol 218 (3) ◽  
pp. 933-937 ◽  
Author(s):  
G Laurent ◽  
F Durant ◽  
J M Frere ◽  
D Klein ◽  
J M Ghuysen
Keyword(s):  
Side Chain ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Sulphur Atom ◽  
Compound I ◽  
Anti Isomer ◽  
Specific Effects ◽  
Acyl Side Chain ◽  
Lactam Ring ◽  
Intrinsic Reactivity

The presence and configuration (syn or anti) of an oxyimino group in the 7 (beta)-acyl side chain of 3-cephems do not modify the intrinsic reactivity of the beta-lactam ring, but have highly enzyme-specific effects. When compared with the corresponding desoxyimino beta-lactam compound: (i) with the plasmid-mediated Escherichia coli RTEM-2 serine beta-lactamase, the substrate activity of the anti isomer is increased and that of the syn isomer is decreased; (ii) with the Streptomyces R61 serine D-alanyl-D-alanine cleaving peptidase (a highly penicillin-sensitive enzyme), the rate of enzyme acylation is not or only little affected when the oxyimino group is in the syn configuration, but is decreased when the oxyimino group is in the anti configuration; (iii) with the Actinomadura R39 serine D-alanyl-D-alanine-cleaving peptidase (an exceedingly highly penicillin-sensitive enzyme), the rate of enzyme acylation is unaffected whatever the configuration of the substituent. The oxidation of the sulphur atom of the dihydrothiazine ring on the beta-face of the molecule makes it both a poorer inactivator of the DD-peptidases and a poorer substrate of the beta-lactamase. The Streptomyces albus G Zn2+-containing D-alanyl-D-alanine-cleaving peptidase (a highly penicillin-resistant enzyme) remains highly resistant to all compounds tested.

scholarly journals Inhibition of class C β-lactamases by (1′R,6R)-6-(1′-hydroxy)benzylpenicillanic acid SS-dioxide

1985 ◽  
Vol 225 (2) ◽  
pp. 435-439 ◽  
Author(s):  
G C Knight ◽  
S G Waley
Keyword(s):  
Side Chain ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Beta Lactamases ◽  
Beta Lactam Antibiotics ◽  
Lactam Ring ◽  
Class C ◽  
Hydrolysis Of

beta-Lactamases, enzymes that catalyse the hydrolysis of the beta-lactam ring in beta-lactam antibiotics, are divided into three classes, A, B and C, on the basis of the structures so far determined. There are relatively few effective inhibitors of class C beta-lactamases. A beta-lactam sulphone with a hydroxybenzyl side chain, namely (1′R,6R)-6-(1′-hydroxy)benzylpenicillanic acid SS-dioxide (I), has now been studied. The sulphone is a good mechanism-based inhibitor of class C beta-lactamases. At pH8, the inhibition of a Pseudomonas beta-lactamase is irreversible, and proceeds at a rate that is about one-tenth the rate of concurrent hydrolysis. The labelled enzyme has enhanced u.v. absorption and is probably an enamine. At a lower pH, however, inhibition is transitory.

Rashes with Ampicillin

1980 ◽  
Vol 1 (7) ◽  
pp. 197-201
Author(s):  
Michael J. Kraemer ◽  
Arnold L. Smith
Keyword(s):  
Penicillin G ◽  
Side Chain ◽  
Gram Negative Bacteria ◽  
Acid Moiety ◽  
Structure Activity ◽  
Body Tissues ◽  
The Family ◽  
Acyl Side Chain ◽  
Penicillanic Acid ◽  
Lactam Ring

Ampicillin, first introduced in 1961, has probably become the most widely used penicillin in clinical pediatrics. STRUCTURE ACTIVITY RELATIONSHIPS All penicillins contain the 6-amino penicillanic acid moiety (Fig 1). Its structure includes a thiazolidine ring (A), a β-lactam ring (B), the source of antibacterial activity, and an acyl side chain (R), containing a variety of substitutions creating the family of semisynthetic penicillins. The only difference between ampicillin and penicillin G is the presence of an amino group in the acyl side chain (Fig 1). PHARMACOLOGY AND BACTERIOLOGY Ampicillin is a semisynthetic penicillin, active against Streptococus pneumoniae and certain Gram-negative bacteria, including most Haemophilus influenzae, Escherichia coli, and certain Proteus species. Compared to penicillin G, it has increased stability in acid solutions: a property facilitating oral administration and absorption. It penetrates into most body tissues; effective entry into CSF, however, occurs only with inflamed meninges. The serum half-life with normal renal function varies from four hours in newborns1 to 1.3 hours in adults.2 Ampicillin can cause an allergic, or nonallergic skin rash (Fig 2). ALLERGY Allergy (for the purposes of this discussion) is defined as a specific immunologic interaction, between either antigen and antibody, or antigen with a sensitized lymphocyte, resulting in a clinically deleterious effect. Implicit is a prior contact with the antigen.

scholarly journals PREVALENCE OF CEPHALOSPORIN-RESISTANT GRAM-NEGATIVE BACILLI FROM CLINICAL SAMPLES

2016 ◽  
pp. 176
Author(s):  
Kavi Aniis ◽  
Rajamanikandan Kcp ◽  
Arvind Prasanth D
Keyword(s):  
Clinical Samples ◽  
Beta Lactamase ◽  
Bacterial Isolates ◽  
Beta Lactam ◽  
Gram Negative ◽  
Beta Lactamases ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Lactam Ring ◽  
Esbl Producers

<p>ABSTRACT<br />Objective: Beta-lactams are the group of antibiotics that contain a ring called as “beta-lactam ring,” which is responsible for the antibacterial activity.<br />The presence of resistance among Gram-negative organisms is due to the production of beta-lactamases enzymes that hydrolysis the beta-lactam ring<br />thereby conferring resistance to the organism. This study is undertaken to determine the prevalence of extended-spectrum beta-lactamase (ESBL)<br />producing Gram-negative organism from clinical samples.<br />Methods: A total of 112 clinical samples were taken for this study. The combined disc synergistic test (CDST) was used for the phenotypic detection<br />of ESBL producers from the clinical samples. The genotypic identification of ESBL producers was carried out by alkaline lysis method by isolation of<br />plasmid DNA.<br />Result: A total of 87 bacterial isolates were isolated and identified. Among them, Klebsiella (41%) was the predominant organism followed by<br />Escherichia coli (33%), Proteus (10%), Pseudomonas (10%), and Serratia (6%). Among the various bacterial isolates, Klebsiella showed a higher<br />percentage of resistance. The CDST showed that 8 isolates of Klebsiella, 3 isolates of E. coli, and 1 isolate of Pseudomonas were found to be ESBL<br />producers. The genotypic confirmation showed that the two bacterial isolates, namely, Klebsiella and E. coli were found to possess temoniera (TEM)<br />gene which was the 400-500 bp conferring resistance to the antibiotics.<br />Conclusion: The results of this study suggest that early detection of ESBL producing Gram-negative organism is a very important step in planning the<br />therapy of patient in Hospitals. CDST continues to be a good indicator in the detection of ESBL producers.<br />Keywords: Beta-lactamases, Gram-negative bacilli, Extended-spectrum beta-lactamase, Resistance, Combined disc synergistic test.</p><p> </p>

Penicillin Update

1995 ◽  
Vol 16 (3) ◽  
pp. 83-90
Author(s):  
Stuart L. Goldstein ◽  
Sheldon L. Kaplan ◽  
Ralph D. Feigin
Keyword(s):  
Cell Wall ◽  
Mechanism Of Action ◽  
Antimicrobial Agents ◽  
Specific Activity ◽  
Basic Structure ◽  
Penicillin G ◽  
Side Chain ◽  
Beta Lactam ◽  
Lactam Ring ◽  
The Stability

Penicillin was discovered serendipitously by Alexander Fleming in 1928 while he was examining Staphylococcus variants. The first trials of penicillin in humans who had serious staphylococcal infections were undertaken more than I decade later and yielded impressive therapeutic results. Despite the introduction of numerous other antimicrobial agents and the emergence of many organisms resistant to penicillin, this agent remains a powerful and essential antibiotic 50 years after its first clinical application. Pharmacology The basic structure of the penicillins consists of the thiazolidine ring, a beta-lactam ring, and a side chain (Figure 1). The antimicrobial activity of all penicillins is produced by the thiazolidine/beta-lactam nucleus, and the organism-specific activity of a particular penicillin is determined by the side chain derivative. There are many naturally occurring side chain derivatives, but penicillin G is the most potent of these and, therefore, the only one used clinically. Semisynthetic penicillins are constructed from the basic penicillin nucleus with a side chain added. Each side chain alters the susceptibility of a particular penicillin to inactivating enzymes. MECHANISM OF ACTION All pencillins work by inhibiting bacterial cell wall synthesis, thereby affecting the stability of the cell wall and subsequent bacterial development. The cell wall is made of a peptidoglycan that is synthesized in three stages. MECHANISM OF ACTION

Characteristics of Aerobacter beta-lactamase

1968 ◽  
Vol 14 (2) ◽  
pp. 139-145 ◽  
Author(s):  
M. Goldner ◽  
D. G. Glass ◽  
P. C. Fleming
Keyword(s):  
Reaction Rates ◽  
Penicillin G ◽  
Cephalosporin C ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Lactam Ring ◽  
Rate Of Hydrolysis ◽  
High Concentrations ◽  
Hydrolysis Of ◽  
Pseudomonas Pyocyanea

In this investigation, Aerobacter cloacae is shown to inactivate cephalosporin by hydrolysis of its beta-lactam ring. This was demonstrated by iodine absorption and infrared absorption spectra.The values of the Michaelis constant obtained with cephalosporin C and deacetyl cephalosporin C indicate a great affinity of the Aerobacter's beta-lactamase for its substrate. The enzyme was most active at pH 7.0 and 37 C. Aqueous washings of the Aerobacter cells were a potent source of enzyme.The beta-lactamase of A. cloacae was active on both cephalosporin and penicillin. A higher rate of hydrolysis was observed with cephalosporin C and deacetyl cephalosporin C than with cephalothin and cephaloridine. The ratio of reaction rates on cephalosporin C to that on penicillin G was consistently of the order of 100 to 1. The activity on V, N, and especially the semisynthetic penicillins was also low.The A. cloacae enzyme was easily demonstrable in large amount without added inducer. By contrast, the activity of the beta-lactamase from Pseudomonas pyocyanea cannot be detected unless high concentrations of inducer are used.

Examination of various Gram-negative bacteria for beta-lactamase activity

1968 ◽  
Vol 14 (5) ◽  
pp. 601-603 ◽  
Author(s):  
Pragna Desai ◽  
M. Goldner
Keyword(s):  
Quantitative Data ◽  
Direct Evidence ◽  
Bacterial Species ◽  
Penicillin G ◽  
Gram Negative Bacteria ◽  
Beta Lactamase ◽  
Infrared Spectrophotometry ◽  
Beta Lactam ◽  
Lactam Ring

The beta-lactamase activity in 10 bacterial species from different genera were evaluated where direct evidence and quantitative data were lacking. A quantitative iodometric method and infrared spectrophotometry were used for the determination of the beta-lactamase activity. The organisms tested were shown to have enzyme activity directed against the beta-lactam ring, and on the basis of the activity on two members of the beta-lactam group of antibiotics, penicillin G and cephalosporin C, a particular ratio was obtained for each species. This report supports the fact of the widespread distribution of beta-lactamase and reopens the question of its significance.

Interaction of β-lactamases I and II from Bacillus cereus with semisynthetic cephamycins. Kinetic studies

1991 ◽  
Vol 279 (1) ◽  
pp. 111-114 ◽  
Author(s):  
J Martin Villacorta ◽  
P Arriaga ◽  
J Laynez ◽  
M Menendez
Keyword(s):  
Bacillus Cereus ◽  
Kinetic Studies ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Beta Lactamases ◽  
Class A ◽  
Rate Determining Step ◽  
Class B ◽  
Lactam Ring ◽  
Beta Lactamase Ii

The influence of C-6 alpha- or C-7 alpha-methoxylation of the beta-lactam ring in the catalytic action of class A and B beta-lactamases has been investigated. For this purpose the kinetic behaviour of beta-lactamases I (class A) and II (class B) from Bacillus cereus was analysed by using several cephamycins, moxalactam, temocillin and related antibiotics. These compounds behaved as poor substrates for beta-lactamase II, with high Km values and very low catalytic efficiencies. In the case of beta-lactamase I, the substitution of a methoxy group for a H atom at C-7 alpha or C-6 alpha decreased the affinity of the substrates for the enzyme. Furthermore, the acylation of cephamycins was completely blocked, whereas that of penicillins was slowed down by a factor of 10(4)-10(5), acylation being the rate-determining step of the process.

scholarly journals Kinetics of inactivation of β-lactamase I by 6 β-bromopenicillanic acid

1980 ◽  
Vol 187 (3) ◽  
pp. 797-802 ◽  
Author(s):  
V Knott-Hunziker ◽  
B S Orlek ◽  
P G Sammes ◽  
S G Waley
Keyword(s):  
Bacillus Cereus ◽  
Rate Constant ◽  
Active Site ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Rate Determining Step ◽  
Competitive Model ◽  
Lactam Ring ◽  
Acid Inactivation ◽  
Kinetics Of

The kinetics of the inactivation of beta-lactamase I from Bacillus cereus 569 by preparations of 6 alpha-bromopenicillanic acid showed unexpected features. These can be quantitatively accounted for on the basis of the inactivator being the epimer, 6 beta-bromopenicillanic acid. At pH 9.2, the rate-determining step in the inactivation is the formation of the inactivator. When pure 6 beta-bromopenicillanic acid is used to inactivate beta-lactamase I, simple second-order kinetics are observed. The inactivated enzyme has a new absorption peak at 326 nm. The rate constant for inactivation has the same value as the rate constant for appearance of absorption at 326 nm; the rate-determining step may thus be fission of the beta-lactam ring of 6 beta-bromopenicillanic acid. Inactivation is slower in the presence of substrate, and the observed kinetics can be quantitatively accounted for on a simple competitive model. The results strongly suggest that inactivation is a consequence of reaction at the active site.

scholarly journals Reversible inhibitors of penicillinases

1978 ◽  
Vol 169 (1) ◽  
pp. 197-204 ◽  
Author(s):  
P A Kiener ◽  
S G Waley
Keyword(s):  
Boric Acid ◽  
Boronic Acid ◽  
Resonance Spectroscopy ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Benzyl Penicillin ◽  
Phenoxymethyl Penicillin ◽  
Reversible Inhibitors ◽  
Competitive Inhibitors ◽  
Lactam Ring

Reversible competitive inhibitors of a penicillinase, beta-lactamase 1 from Bacillus cereus, were studied. These represent the first inhibitors of a penicillinase that lack the beta-lactam ring. The products of the enzymic reaction, namely penicilloic acids, are inhibitors; their decarboxylation products, the penilloic acids, are also inhibitors, and have somewhat lower Ki values. Inhibitors have been prepared from benzylpenicillin, phenoxymethyl-penicillin, methicillin (2,6-dimethoxybenzamidopenicillanic acid) and 3-hydroxy-4-nitrobenzamidopenicillanic acid. Decarboxylation of the penicilloic acids from benzyl-penicillin, or from phenoxymethylpenicillin, leads to epimerization (at C-5) of the penilloic acid. Nuclear-magnetic resonance spectroscopy at a frequency of 270 MHz can distinguish the epimers. Other competitive inhibitors studied were boric acid, benzene boronic acid and m-aminobenzeneboronic acid. Boric acid itself was the best inhibitor of beta-lactamase I so far found.

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