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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.

Protein synthesis in the mycelium of various ages and the protoplasts of Str. erythreus 1571 was slightly sensitive even to high concentrations of erythromycin and lincomycin. Oxytetracycline and neomycin in low concentrations induced marked inhibition of the protein synthesis. 14C-Erythromycin was binding with the mycelium of the organism producing it in much lower amounts than with the mycelium of Str. roseolus, a lincomycin-producing culture. No products of erythromycin biotransformation by the cell-free preparations of Str. erythreus containing cofactors for enzymatic phosphorylation and demethylation were detected with the methods of microbiological titration and radiochromatography. Enzymatic N-demethylation of lincomycin was observed in the cell-free preparations of Str. erythreus. Erythromycin and lincomycin had practically no effect on polylysine synthesis in the cell-free system of Str. erythreus with poly-A and inhibited the synthesis of this polypeptide in the cell-free systems of E. coli MRE 600 and B. subtilis ATCC 6633. These antibiotics had either no effect on the fragment (puromycin) reaction with the ribosomes of Str. erythreus. In case of the ribosomes of E. coli MRE 600 the fragment reaction was sensitive to lincomycin but not to erythromycin. The ribosomes isolated from Str. erythreus and their 50S subunits bound 14C-erythromycin in much lower amounts than those isolated from E. coli and their 50S subunits. The data are indicative of the presence of 2 systems protecting the culture from erythromycin in Str. erythreus 1571, i.e. at the level of ribosomes and at the level of the cytoplasmic membrane.

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.

The results of the study on the inhibitory effect of a number of rifamycin derivatives, such as rifamycin B, rifamycin O, rifamycin, rifamycin A, 25-desacetylrifampicin and rifampicin are presented. It was shown that rifampicin had the highest inhibitory effect on the synthesis of RNA in the cells of E. coli and Staph. aureus. It inhibited the above process by 93.0 and 98.8 per cent respectively. The data on the cells of Staph. aureus, as well as the data on comparison of the inhibitory effect of rifampicin derivatives with respect to the RNA-polymerase reaction in acellular systems are presented.

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.

Comparison of sodium methicillin samples irradiated and not-irradiated with fast electrons (10 Me V, 2.5 Mrad) showed no differences with respect to the content of the active substance and a number of physico-chemical properties according to the USSR State Pharmacopoeia, Xed. Yet, the irradiated samples did not meet the requirements for powder appearance, colour and solution transparence.

The study on distribution of 14C-rifampicin administered intramuscularly to pregnent animals showed that its concentrations in the blood, liver, kidneys, lungs and other organs did not practically change from those in nonpregnant animals. The concentration of 14C-rifampicin in the fetus organs was much lower than that in the organs of the adult animals. The liver and kidneys of the pregnant animals, as well as the fetus though to a less extent had a capacity for metabolism of 14C-rifampicin. The following products of biotransformation were detected: N-oxide of rifampicin, 25-deacetylrifampicin, 3-formylrifamycin SV and rifamycin SV.

The study on distribution of 14C-rifampicin and 14C-rifamycin S in experimental animals after intramuscular administration of the drugs showed that concentrations of rifampicin in the organs and blood were higher than those of rifamycin S. Biotransformation products of both antibiotics, such as 25-deacetylrifampicin, N-oxide of rifampicin, 3-phormylrifamycin SV, rifamycin SV and others were found in the liver, kidneys, bile and urine. No products of the antibiotic metabolism were found in the blood, lungs and spleen.

The results of studying the effectiveness of incorporation of the label from different 14C- and 3H-precursors into the molecule of rifamicin B during its biosynthesis are presented. The regularities of the label incorporation into the antibiotic composition as dependent on the time of the precursor addition were investigated. A radiochemically pure preparation of 14C-rifamicin B with specific radioactivity of 3 mcurie/mg was obtained.

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.