S U M M A R YCysteine appeared to have two classes of growth inhibitory effect onEscherichia coli: (I) above 0.2 m i t inhibited growth on minimal medium by a mechanism which may involve interference with leucine, isoleucine, threonine and valine biosynthesis ; ( 2 ) above 2 mM, in media with these amino acids, it had an effect which may involve interaction with membrane bound respiratory enzymes.Cysteamine showed only effect ( 2 ) . I N T R O D U C T I O NRoberts, Abelson, Cowie, Bolton & Britten (1957) reported that exogenous cysteine inhibits the growth of Escherichia coli, but the mechanism of this action is still unclarified. Nagy, Hernadi, Kovhcs, Valyi-Nagy (1968a) and Nagy, Kovacs, Kari & Hernidi (1970) found that, in E. coli 1 5~-, the net synthesis of RNA and protein, but not that of DNA, was quickly inhibited by cysteine. An antagonism could be detected between cysteine and leucine (leu), isoleucine (ileu), threonine (threo) and valine (Val) and it was suggested that the biosynthesis of these amino acids (AAs) is inhibited by cysteine (Kovhcs, Kari, Nagy & Hernidi, 1968). However, not all the effects of cysteine could be explained in this way (Nagy, Kari & Hernadi, 1969 Hernadi, 1971). Each of these effects may be responsible for its cytotoxic action, but it is difficult to demonstrate which of these many reactions is involved in growth inhibition. Enzyme experiments in vitro and the various metabolic actions of cysteine need to be assessed in the light of detailed growth studies. M E T H O D SBacterial strains, Escherichia coli strain B (prototroph, from T. Alper of Hammersmith Hospital, London) ; Hfr CAVALLI met-rel-(a relaxed strain, auxotrophic for methionine) ; CP 99 his-arg-ser-Bl-reE+ (a stringent strain, auxotrophic for histidine, arginine, serine and B~) ; and CPIOO his-arg-ser-B,-rel-(a relaxed mutant of ~~9 9 ) .The latter three strains were obtained from L. Alfoldi (Medical University of Szeged, Hungary).Growth. Organisms were cultivated on mineral salts medium C (Roberts et al. 1957)

We studied the inhibitory effects on colony formation by granulocyte-macrophage colony forming units (cfu-gm) of eight azole antifungal agents in vitro. All agents, except fluconazole, inhibited colony formation dose-dependently with 50% inhibitory concentrations (IC50) in the range of 0.78-49 micromol/L in cultures of murine and human bone marrow. For human cells, the IC50 values were 0.553 mg/L for itraconazole, 1.24 mg/L for saperconazole, 2.58 mg/L for clotrimazole, 5.33 mg/L for miconazole, 6.17 mg/L for econazole, 6.27 mg/L for ketoconazole and 8.38 mg/L for oxiconazole. The IC50 of itraconazole for human cfu-gm in vitro was similar to the plasma level of this drug recommended for systemic antifungal therapy (>0.5 mg/L) thus indicating the potential clinical relevance of our data. The IC50 of ketoconazole for human cfu-gm in vitro may be exceeded by plasma levels produced in vivo by high (> or =400 mg) doses, whereas fluconazole failed to reduce colony formation by 50% even at 100 mg/L, a concentration not reached in vivo even after extremely high doses (2000 mg/day). To most of the drugs studied, murine progenitor cells seemed to be less sensitive than the human ones. There was, however, a close correlation between the murine and human log IC50 values of the drugs (r2 = 0.964, P< 0.001), suggesting that cultures of murine bone marrow may be suitable to predict the in-vitro toxicity of azole antifungals to human cfu-gm.

No abstract

The antibacterial activity of BK-218 was similar to that of cefamandole when it was tested against several laboratory strains. The inhibiting effect of BK-218 was greater than that of cephalexin and cefoxitin on penicillin-binding proteins of Escherichia col HB101. This result was in close correlation with the relative inhibition of radiolabeled glucosamine incorporation (greatest with BK-218) and with the lytic effect (most intensive with BK-218). BK-218 proved to be a good inhibitor for all five of the ,-lactamases that were investigated, although two enzymes (Enterobacter cloacae P99 and Pseudomonas aeruginosa Cilote) hydrolyzed it to some extent.Cephalexin (4), cefadroxil (7), cefaclor (4,21), cefroxadine (34), and cefatrizine (22) (Fig. 1.), is a new oral cephalosporin.It is well-known that beta-lactam antibiotics first bind to their targets, the so-called penicillin-binding proteins (PBPs). The inhibition of these enzymes suspends peptidoglycan synthesis, and as a consequence the autolytic enzymes are triggered with a mechanism whose details are not completely understood (16).The purpose of this study was to report the results of preliminary investigations concerning the in vitro activity of BK-218 against a limited number of gram-positive and gramnegative bacteria. The MICs of BK-218 were compared with those of other parenteral (cefuroxime, cefamandole, and cefoxitin) and oral (cephalexin) antibiotics.The in vitro effect on the targets was measured by (i) affinity to PBPs, (ii) incorporation of labeled glucosamine into the cell wall of Escherichia coli, and (iii) release of labeled glucosamine-containing fragments from prelabeled cell wall of E. coli to assess the lysis capability of BK-218.

Background: Mechanisms of borderline resistance of Staphylococcus aureus to penicillinase-resistant penicillins (PRPs) may include hyperproduction of classical penicillinase and/or production of β-lactamase hydrolyzing also PRPs. Methods: β-Lactamase activity of whole cells and purified enzymes was estimated spectrophotometrically and in isolated cytoplasmic membranes by bioassay with Bacillus subtilis as test strain. Results: Out of 53 clinical isolates of S. aureus, 18 showed oxacillin MIC values from 0.5 to 2 µg/ml, which were reduced by sulbactam and/or clavulanic acid in the case of four isolates producing large quantities of inducible, type A β-lactamase. Cytoplasmic membranes isolated from these strains showed oxacillin-hydrolyzing activity. One of these strains was grown also in the presence of globomycin, an antibiotic known to interfere with the anchorage of membrane lipoproteins; this treatment eliminated the oxacillin-hydrolyzing activity. Conclusions: The resistance in these strains was due to a membrane-bound lipoprotein with oxacillin-hydrolyzing activity.