Interaction between β‐Lactam Antibiotics and Exocellular <scp>dd</scp>‐Carboxypeptidase‐Transpeptidase of <i>Streptomyces</i> R61

Frère, Jean‐Marie; Leyh‐Bouille, Mélina; Ghuysen, Jean‐Marie; Perkins, H. R.

doi:10.1111/j.1432-1033.1974.tb03889.x

Cited by 44 publications

(20 citation statements)

References 12 publications

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“…In conclusion, cephalexin, a ␤-lactam compound and an active site-directed inactivator of PBPs (11), forms an acyl enzyme with the serine residue in the active site (13). In contrast, arylalkylidene rhodanine derivative 2 behaves as a noncompetitive inhibitor of PBP 2xS and probably does not interact with the active site of this enzyme.…”

Section: Vol 48 2004 Two Novel Classes Of Pbp Inhibitors 967mentioning

confidence: 99%

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Interactions between Penicillin-Binding Proteins (PBPs) and Two Novel Classes of PBP Inhibitors, Arylalkylidene Rhodanines and Arylalkylidene Iminothiazolidin-4-ones

Zervosen

Lu²,

Chen

et al. 2004

Antimicrob Agents Chemother

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Several non-␤-lactam compounds were active against various gram-positive and gram-negative bacterial strains. The MICs of arylalkylidene rhodanines and arylalkylidene iminothiazolidin-4-ones were lower than those of ampicillin and cefotaxime for methicillin-resistant Staphylococcus aureus MI339 and vancomycinresistant Enterococcus faecium EF12. Several compounds were found to inhibit the cell wall synthesis of S. aureus and the last two steps of peptidoglycan biosynthesis catalyzed by ether-treated cells of Escherichia coli or cell wall membrane preparations of Bacillus megaterium. The effects of the arylalkylidene rhodanines and arylalkylidene iminothiazolidin-4-one derivatives on E. coli PBP 3 and PBP 5, Streptococcus pneumoniae PBP 2xS (PBP 2x from a penicillin-sensitive strain) and PBP 2xR (PBP 2x from a penicillin-resistant strain), low-affinity PBP 2a of S. aureus, and the Actinomadura sp. strain R39 and Streptomyces sp. strain R61 DDpeptidases were studied. Some of the compounds exhibited inhibitory activities in the 10 to 100 M concentration range. The inhibition of PBP 2xS by several of them appeared to be noncompetitive. The dissociation constant for the best inhibitor (K i ‫؍‬ 10 M) was not influenced by the presence of the substrate.

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Section: Vol 48 2004 Two Novel Classes Of Pbp Inhibitors 967mentioning

confidence: 99%

“…strain R61 (11,15) and Actinomadura sp. strain R39 (14) have DDpeptidase, esterase, and thiolesterase activities.…”

Section: Vol 48 2004 Two Novel Classes Of Pbp Inhibitors 967mentioning

confidence: 99%

Interactions between Penicillin-Binding Proteins (PBPs) and Two Novel Classes of PBP Inhibitors, Arylalkylidene Rhodanines and Arylalkylidene Iminothiazolidin-4-ones

Zervosen

Lu²,

Chen

et al. 2004

Antimicrob Agents Chemother

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“…The effect of penicillin on bacteria is well known (5). It affects streptomycetes as well (5,6), although S. griseus has not been extensively investigated in this respect.…”

Section: Resultsmentioning

confidence: 99%

“…It affects streptomycetes as well (5,6), although S. griseus has not been extensively investigated in this respect. In preliminary experiments, the subinhibitory concentration of penicillin for our strain at different ages was determined.…”

Section: Resultsmentioning

confidence: 99%

Effect of Penicillin on Streptomycin Production by Streptomyces griseus

Barabás

Szabó

1977

Antimicrob Agents Chemother

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The correlation between the biosynthesis of the cell wall and the formation of streptomycin (SM) in Streptomyces griseus, influenced by a specific inhibitor of cell wall synthesis, was investigated. Penicillin, in subinhibitory concentrations (1 to 5 ,ug/ml), was added to cultures of S. griseus in different stages of its life cycle. The inhibitor decreased SM production, when young cultures were treated; however, there was an increase in SM formation when penicillin was added to older cultures. The explanation for these findings is discussed in detail.The physiological role of streptomycin (SM) in the life of Streptomyces griseus has been investigated. We proved that streptidine (SD), a component of the SM molecule, is a constituent of the cell wall (2, 10). This indicates that SM or its SD component plays a role in building up the cell wall network (1,(8)(9)(10). These findings prompted us to search for correlations between cell wall synthesis and SM production in S. griseus. Use of specific inhibitors of cell wall synthesis in bacteria, such as penicillin, bacitracin, etc., seemed promising as an approach to the problem (Gy. Barabas, Folia Microbiol. 18:266, 1973). Since SD is a component of cell walls, one might expect that the inhibition of cell wall synthesis would change SM production.In this paper, we describe the effects on SM production by S. griseus cultures when penicillin is added at different stages in the S. griseus life cycle. MATERLALS AND METHODSStrains and cultivation. S. griseus LS-1 (code no. 52-1) strain was used. Its cultural and physiological characteristics, as well as the composition of the filtered soybean medium employed throughout the experiments, were previously described (8). Cultivation was carried out on a rotary shaker (250 rpm, 50-mm stroke distance) at 270C.Antibiotic assay. SM content of the fermentation liquid was determined by the agar-hole diffusion method against Bacillus subtilis ATCC 6633. The fermentation liquid was spun down, and the cellfree supernatants were diluted with 0.067 M phosphate buffer (pH 7.5) containing penicillinase (Neutrapen Riker Laboratories, Loughborough, England, in a final concentration of 100 ,ug/ml). The samples were incubated at 37°C for 1 h to inactivate penicillin. Then, four to seven replicates were pipetted in the holes of agar plates from every sample, and their mean was used for the calculation. The agar medium for antibiotic assay was prepared as follows: 5 g of meat extract, 1 g of Na2HPO4, 0.1 g of KH2PO4, and 0.5 g of peptone were dissolved in 100 ml of distilled water and boiled for 2 min. After filtration, 900 ml of distilled water was added, as well as 20 g of agar. The pH of the medium was adjusted to 7.0 after it had melted, and it was finally sterilized by autoclaving. The melted medium was inoculated with B. subtilis, poured into petri plates, and incubated at 37°C for 1 h. Samples were then pipetted into the holes. The inhibition zone of the antibiotic was measured after 20 h of incubation at 37°C. Control experiments showed ...

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“…The values of the k 2 / K and k3 parameters, which govern the interaction between benzylpenicillin and the enzyme under consideration, were estimated according to F r k e et al [25,26]. Preliminary experiments showed that the benzylpenicillin concentrations required to inhibit the uwarboxypeptidase activity by 50% were 0.014 pM for the 54000-M, enzyme and 0.14pM for the 40000-M, enzyme.…”

Section: Efsicacy Of Trunspeptidation By the Exocellular 54000-mimentioning

confidence: 99%

On the dd-Carboxypeptidase Enzyme System of Streptomyces Strain K15

Leyh‐Bouille

Nguyen-Distèche

Ghuysen

2005

European Journal of Biochemistry

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Streptomyces KIS possesses a set of exocellular and cell-bound D-alanyl-D-alanine carboxypeptidases. Four of them have been isolated to the stage where each enzyme preparation contains one single penicillin-binding protein. The exocellular 54000-M, enzyme is extremely sensitive to benzylpenicillin and performs low transpeptidase activity on the carbonyl-donor/amino-acceptor tetrapeptide AcLLys(G1y)-DAla-DAla. The exocellular 40000-M, enzyme and the two lysozyme-releasable 40000-M, and 38000-M, enzymes are moderately sensitive to benzylpenicillin and have a high propensity to catalyse dimer formation from the aforementioned tetrapeptide monomerThe D-alanyl-D-alanine carboxypeptidases are enzymes involved in the crosslinking step of bacterial cell wall synthesis [l]. They catalyse attack, by a suitable exogenous nucleophile, of the carbonyl carbon of the DAla-DAla amide bond of LXaa-DAIa-DAia-terminated peptides, where Xaa is most often a diamino acid residue. These enzymes exhibit widely varying molecular weights, sensitivities to fl-lactam antibiotics, specificity profiles for the carbonyl-donor peptides and abilities to use amino compounds as nucleophilic acceptors of the LXaa-DAla moieties in transpeptidation reactions [2]. In addition, they can operate by at least two different mechanisms : four serine DD-carboxypeptidases [3 -51 and one Zn2+ DD-carboxypeptidase [6,7] are known. A survey, carried out under standard but arbitrary conditions, of the activities performed by the culture filtrates obtained from various strains of actinomycetes, led to the isolation of the very highly penicillin-sensitive, 53 OOO-M, R39 DD-carboxypeptidase (from Actinomudura R39) [4], the moderately penicillin-sensitive, 38 OOO-M, R61 DD-carboxypeptidase (from Streptomyces R61) [3], and the highly penicillin-resistant 18 000-M,G DDcarboxypeptidase (from Streptomyces ulbus G) [6-71. The R61 and R39 enzymes are serine peptidases; they are able to perform transpeptidation reactions. The G enzyme is a Zn2+ peptidase; it functions only as a hydrolase. The question whether the R61, R39 and G enzymes were strain-specific or not has been examined. It has been found that Streptomyces strain K1S excretes and/or possesses, bound to its cell envelope, a set of DD-carboxypeptidases. On the basis of their penicillin sensitivities and substrate requirements, one of them is a R39-like enzyme and the others are R61-like enzymes. MATERIALS AND METHODS on-Curboxypeptidase Transpeptidase AssaysThe procedures used were those described previously [8,9]. Unless otherwise stated, the substrate concentrations were : 1.8 mM AczLLys-DAla-DAla (Du-carboxypeptidase activity ; reaction catalysed: AczLLys-uAla-DAla + H2O -+ DAla ~~ Ahhreviutions. AcMur, N-acetylniuramic acid; A2pm, meso-2,2'-diaminopimelic acid; AcLys, Nu-acetyllysine; Hepes, 4-(2-hydroxyethyl)-1 -piperazineethanesulphonic acid.

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Interaction between β‐Lactam Antibiotics and Exocellular dd‐Carboxypeptidase‐Transpeptidase of Streptomyces R61

Cited by 44 publications

References 12 publications

Interactions between Penicillin-Binding Proteins (PBPs) and Two Novel Classes of PBP Inhibitors, Arylalkylidene Rhodanines and Arylalkylidene Iminothiazolidin-4-ones

Interactions between Penicillin-Binding Proteins (PBPs) and Two Novel Classes of PBP Inhibitors, Arylalkylidene Rhodanines and Arylalkylidene Iminothiazolidin-4-ones

Effect of Penicillin on Streptomycin Production by Streptomyces griseus

On the dd-Carboxypeptidase Enzyme System of Streptomyces Strain K15

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