Tyrothricin

Abstract: Tyrocidine is a cyclic decapeptide antibiotic which is produced and secreted by stationary-phase cells of the sporeforming bacterium Bacillus brevis. We identified the promoter for the B. brevis structural gene (tycA) for tyrocidine synthetase I, the enzyme catalyzing the first step in tyrocidine biosynthesis, and studied its regulation in cells of B. brevis and Bacillus subtilis. Transcription from the tycA promoter was induced at the end of the exponential phase of the growth cycle in B. brevis cells growing in sporulation medium. To study the regulation of tycA in B. subtilis, we constructed a derivative of the B. subtilis bacteriophage SP beta containing a transcriptional fusion of the tycA promoter to the lacZ gene of Escherichia coli and introduced the tycA-lacZ operon fusion by means of specialized transduction into sporulation mutants known to be blocked in sporulation-associated antibiotic production. Our principal finding was that tycA-directed lacZ expression was impaired in the stage-0 mutants with mutations spo0A, spo0B, and spo0E but not in spo0C, spo0F, spo0H, or spo+ bacteria. The dependence on the spo0A gene product could be entirely bypassed by an abrB suppressor mutation, which caused tycA-lacZ to be transcribed constitutively at all stages of growth. A simple model is proposed for the mechanism of tycA induction based on the Spo0A-dependent inactivation of Ab-B protein, which is proposed to be a negative regulator of tycA transcription.

Abstract: Tyrothricin specifically inhibits RNA synthesis in growing cultures of Bacillus brevis as well as purified RNA polymerase. This suggests that the peptide antibiotic may function in the regulation of gene transcription during the transition from vegetative growth to sporulation.

Abstract: Since Pasteur first demonstrated that certain micro6rganisms are able to exert antagonistic or antibiotic effects upon other organisms, an extensive literature has accumulated (Waksman, 1941). The presence of living organisms is often necessary for the phenomenon of antagonism to take place. In many cases, the antagonist was found to produce an active substance responsible for this action. The active agent has been isolated, purified, and crystallized only in very few instances. Pyocyanase was the first antagonistic substance to have thus been obtained (Emmerich and Low, 1899). Several others have been isolated recently. Certain facts have now become recognized concerning the nature of the phenomenon produced by antagonistic microorganisms: 1. The various active substances isolated from the different organisms vary considerably in their chemical nature; 2. these substances are selective in their action upon various organisms, showing variation even as regards specific types or strains of the different groups of bacteria acted upon; 3. the substances vary in the mechanism of their action, some being primarily bacteriostatic, and others bactericidal but not bacteriolytic, whereas still others are both bactericidal and bacteriolytic; 4. the antagonistic capacity is widely distributed among microorganisms and is not limited to any one group of bacteria or fungi. Active antibiotic agents have now been obtained from representative types of spore-forming bacteria, non-spore-forming bacteria, actinomycetes and fungi. Some of these agents have not yet been isolated in a pure state; however, they are well recognized, both chemically and biologically, and can be characterized by their specific properties. The following substances or preparations have received the greatest consideration: 1. pyocyanase, 2. pyocyanin, 3. gramicidin, 4. tyrocidine, 5. penicillin, 6. gliotoxin, 7. actinomycin, and 8. streptothricin. The first four are of bacterial origin, the next two are produced by fungi, and the last two by actinomycetes. To these may be added several other preparations, of which the exact chemical nature or mode of action is less known, namely, actinomycetin, prodigiosin, fluorescin, microbial-lysozyme, active substances obtained from species of Aspergillus and from various other fungi and bacteria. Among the antagonistic phenomena which are now well recognized but for which no active substance has as yet been demonstrated, one may men-

Abstract: 17 antibiotics, with potential for topical use, were tested for their activity against the human oral flora. Concentrations (mumol/l) required to inhibit 90% of test strains are presented and drug activities are compared. The total cultivable oral flora was susceptible to the tetracyclines including tetracycline itself, minocycline, doxycycline, and oxytetracycline and to erythromycin. On the other hand, actinobolin, kanamycin, neomycin, streptomycin, spiramycin, tyrothricin, vancomycin, clindamycin, and chloramphenicol were ineffective against many of the human oral anaerobic bacteria even at high concentration. Penicillin was effective at high concentrations but could not be recommended because organisms which are not inhibited by low concentrations are penicillinase producers. Carbenicillin was effective against all organisms except Actinobacillus actinomycetemcomitans. The gram-negative organisms involved in adult periodontitis were most susceptible to the tetracyclines, tyrothricin, carbenicillin and clindamycin, while those associated with localized juvenile periodontitis were susceptible to the tetracyclines or erythromycin. These data, combined with the previous findings that some tetracyclines exhibit marked substantivity and collagenase inhibition activity, indicate that tetracycline or minocycline are likely to be good choices in the treatment or prevention of oral diseases.