[A comparative study of liposome-incorporated beta-lactam antibiotics, fluoroquinolones and cephalosporin conjugates with fluoroquinolones]. / Sravnitel'noe izuchenie vkliucheniia v liposomy betalaktamnykh antibiotikov, ftorkhinolonov i kon''iugatov tsefalosporinov s ftorkhinolonami.

Beta-lactam antibiotics (some penicillins and cephalosporins), a fluorquinolone (pefloxacin) and cephalosporin conjugates with fluorquinolones were liposome-encapsulated by the method of detergent dialysis. Under the experimental conditions the entrapment of the beta-lactams and pefloxacin to liposomes did not exceed 20 and 12.5 per cent of the initial quantity respectively. The liposome entrapment of the cephalosporin conjugates with fluorquinolones was much higher. The entrapment of the cefotaxime conjugate with ciprofloxacin amounted to 40 per cent and that of the cefamandol conjugate with pefloxacin amounted to 95 per cent of the initial quantity.

[Inactivation of free and liposome-encapsulated aminoglycosides by enzymes of resistant strains of bacteria]. / Izuchenie inaktivatsii svobodnykh i vkliuchennykh v liposomy aminoglikozidov fermentami rezistentnykh shtammov bakterii.

Liposome-encapsulated gentamicin, sisomicin, paromomycin, amikacin, dibekacin and some other aminoglycoside antibiotics were prepared by the method of detergent dialysis. The entrapment level was higher with respect to paromomycin, gentamicin and sisomicin. After a 1-hour incubation of the liposome-encapsulated paromomycin in the presence of a cell-free preparation of 3'-1-phosphotransferase from Escherichia coli there was observed no inactivation of the antibiotic. Free paromomycin incubated under the same conditions in the presence of the enzyme was inactivated by 50 per cent. After a 3-hour incubation of paromomycin in the presence of 3"-1-phosphotransferase the antibiotic activity in the incubation mixture was not detected. The liposome-encapsulated paromomycin preserved about 50 per cent of the activity after its 18-hour incubation in the presence of the enzyme. Inactivation of gentamicin by a cell-free preparation of 2"-adenylyltransferase (Salmonella oranienburg 1376) was also markedly lowered when it was used encapsulated in liposomes.

[Isolation and characteristics of mitochondrial DNA from Acremonium chrysogenum]. / Vydelenie i kharakteristika mitokhondrial'noí DNK iz Acremonium chrysogenum.

Circular mDNAs 26.85 and 26.94 kb in length were isolated from two isogenic strains of A. chrysogenum producing cephalosporin C. The strains differed in antibiotic production capacity. Restriction analysis of the mDNAs was performed with using 6 endonucleases. Comparison of the restriction data revealed identity of mDNAs. A restriction map of the mDNAs was constructed. It is useful as a basis for further studies with molecular cloning.

[Penicillin-binding proteins of various strains of Lactobacillus]. / Penitsillinsviazyvaiushchie belki nekotorykh vidov laktobatsill.

Sensitivity of different species of Lactobacillus i.e. L. casei, L. plantarum, L. acidophillus, L. buchneri, L. jugurti and others to penicillins and cephalosporins of various generations was studied. Penicillin binding proteins (PBPs) of the Lactobacillus species were specified. It was shown that the number of PBPs depended on the Lactobacillus species. L. casei had the least number of PBPs (4) and L. brevis had the highest number of PBPs (11). Competition of 14C-benzylpenicillin with ampicillin, cefotaxime, ceftizoxime and cefoperazone for binding to separate PBPs in three strains of different Lactobacillus species was investigated.

[Effect of aminoglycosides on the binding of C14-benzylpenicillin by penicillin-binding proteins in Escherichia coli]. / Vliianie aminoglikozidov na sviazyvanie C14-benzilpenitsillina penitsillinsviazyvaiushchimi belkami Escherichia coli.

It was shown that preincubation of E. coli intact cells with gentamicin and streptomycin induced a marked increase in binding of 14C-benzylpenicillin to its final targets in the membrane i.e. penicillin-binding proteins (PBP). The stimulating effect of the aminoglycosides was also confirmed in experiments with a membrane fraction isolated from the cells preincubated with the aminoglycosides. The PBPs of the cells preincubated with the aminoglycosides were studied with SDS-PAAG electrophoresis. It was revealed that under the action of the aminoglycosides the quantity of the labeled substance (intensity of the bands on the fluorograms) fixed by the low molecular PBPs i.e. D-alanine carboxypeptidases increased. Moreover, the composition of the high molecular less mobile PBPs (transpeptidases) changed. The data are discussed in regard to the peculiarities of the effect of the aminoglycosides on the cells (bactericidal action, membrane tropism). The effect of the aminoglycosides can influence (along with the others) the results of their combined use with beta-lactams.

[Competitive binding of various beta-lactam compounds to penicillin-binding proteins of Escherichia coli]. / Konkurentnoe sviazyvanie nekotorykh betalaktamnykh soedinenii s penitsillinsviazyvaiushchimi belkami Escherichia coli.

Competing interaction of two novel N-acyl derivatives of ampicillin i.e. N'-benzylchlorbenzimidazole (No. 48) and N-pyrazolytiazole (No. 72) derivatives and 14C-benzylpenicillin with penicillin-binding proteins (PBP) of E. coli was studied. It was shown that ampicillin and its derivative No. 48 markedly differed in their affinity to various PBPs. Derivative No. 72 did not prevent binding of the labeled benzylpenicillin to any PBP which corresponded to its low antimicrobial activity. Analogous experiments with new cephalosporin structures i.e. active and inactive N-acyl derivatives of cephalosporin showed that the active derivative No. 94 i.e. N-methyltiobenzimidazole derivative had the highest affinity to PBP-2 and PBP-5. The inactive derivative No. 68 i.e. N-chlorbenzimidazole derivative also had high affinity to PBP-1b, PBP-2 and PBP-3 essential for the cell. No activity of the latter compound against intact cells of E. coli was probably due to its low penetration through the outer membrane of the bacterial cell. Estimation of affinity of the beta-lactam structures to various PBPs not only provided data on the mechanism of their action but also made it possible to explain in some cases the peculiarities of their antimicrobial spectrum.

[Comparative characteristics of penicillin-binding proteins of representatives of the genus Streptomyces]. / Sravnitel'naia kharakteristika penitsillinsviazyvaiushchikh belkov predstavitelei roda Streptomyces.

Penicillin-binding proteins (PBPs) in Strepomyces strains producing clavulanic acid and beta-lactamase and in Streptomyces strains not producing these compounds were studied comparatively. In S. clavuligerus, the organism producing clavulanic acid, there were detected 3 PBPs in the membrane fraction. S. griseus, the organism producing beta-lactamase, contained 6 PBP. In S. cacaoi and S. olivaceus, organisms producing neither beta-lactams nor beta-lactamase, there were detected 5 and 4 PBP, respectively. The set of the PBP in the organism producing clavulanic acid varied during fermentation. In a variant of S. clavuligerus isolated after protoplasting of the mycelial cells and their regeneration the content of the electrophoretically most mobile PBP lowered. The PBP of S. clavuligerus did no show any high affinity to other beta-lactams such as methicillin and ampicillin tested as competing agents of 14C-benzylpenicillin.