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Cladosporin was isolated from the cultures of three species of the genus Eurotium. Cladosporin inhibited the growth of several fungi and at very low concentrations the growth of Bacillus brevis and Clostridium pasteurianum. Bacillus subtilis and most other Gram-positive bacteria were not sensitive. Gram-negative bacteria and yeasts were not affected by concentrations up to 100 microgram/ml. Dimethyl cladosporin showed only week activity against Bacillus brevis with the minimal inhibitory concentrations being a 100 times higher than of cladosporin. The incorporation of leucine and uracil into acid insoluble material in Bacillus brevis cells was completely inhibited by concentration of 0.5 microgram/ml cladosporin. The incorporation of thymidine was not affected at this concentration.

On the basis of kinetic studies on glucosamine-6-phosphate synthetase (EC 5.3.1.19) from six bacteria sources it has been shown that the epoxyamino acid anticapsin, a glutamine analog, is a competitive inhibitor of the enzyme in regard to glutamine with Km value of 10(-4) M and Ki varying from 10(-7) to 10(-6) M. Unlike other glutamine analogs like 6-diazo-5-oxo-L-norleucine, chloropentanoic acid, L-alpha-amino-3-chloro-4,5-dihydro-5-isoxazole acetic acid or albizziin, anticapsin is not generally inhibitory to various amidotransferases. It does not inhibit xanthosine 5'-monophosphate amidotransferase, glutaminase or gamma-glutamyltranspeptidase.

The clavams valclavam and hydroxyethylclavam were both bacteriostatic and fungistatic. The molecular basis for growth inhibition of Escherichia coli was a non-competitive inhibition of homoserine-O-succinyltransferase (EC 2.3.1.46), thus blocking methionine biosynthesis. Eucaryotes such as Saccharomyces cerevisiae were inhibited by a different mode of action. Instead of interfering with methionine biosynthesis, the clavams inhibited the formation of RNA in living cells, although the RNA-polymerases of isolated yeast nuclei were not inhibited. The action of valclavam on E. coli was dependent on functional peptide transport systems.

The extreme chemical heterogeneity of antimicrobial inhibitors may be compared with the large heterogeneity of the sites of attack. From the host of questions regarding the mechanism of action three problems are selected at random for discussion: 1. Penetration or transport of inhibitors into the cell. At least some of the inhibitors must penetrate into the cell and find their way to very specific points of action; and it does not go without saying that the antibiotics reach their targets without previously reacting with other cell components or without being "trapped" by the cytoplasmic membrane. In some instances an active transport, i.e. a "misuse" by antibiotics of a transport system for a substrate can be demonstrated. 2. Distribution of the targets in the cell. Distribution of the inhibitors over the possible targets is not uniform. The question why this is so remains unanswered. 3. The membrane as the point of attack for inhibitors. The probability that an inhibitor has a bactericidal effect also on resting cells is greatest with substances that act on the membrane. The question as to the function of the antibiotics for the active cell arises and the "defence function" of the antibiotics is called in question.