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Tyrothricin
Published in Anton C. de Groot, Monographs in Contact Allergy, 2021
Tyrothricin is an antibiotic peptide complex produced and extracted from the aerobic gram-positive bacterium Brevibacillus parabrevis, which was previously categorized as Bacillus brevis and Bacillus aneurinolyticus. This complex is a mixture comprised of 60% tyrocidine cationic cyclic decapeptides (consisting largely of the six predominant tyrocidines, TrcA/A1, TrcB/B1, TrcC/C1, and other more minor contributors) and 40% neutral linear gramicidins (where valine-gramicidin A is often the major gramicidin present). Tyrothricin possesses broad spectrum gram-positive antibacterial and antifungal activity. The antibiotic mixture is very toxic to blood, liver, kidneys, meninges, and the olfactory apparatus, but is sometimes used topically in sore throat medications and in agents for the healing of infected superficial and small-area wounds (1).
Bacitracin and Gramicidin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
The first clinically tested antibiotic was isolated from Bacillus brevis by Dubos in 1939 and named tyrothricin (Hotchkiss and Dubos, 1940; Dubos and Hotchkiss, 1941). Later it was shown that tyrothricin consisted of two antibiotics, gramicidin and tyrocidine. Gramicidin was the more active drug of the two and consists of a group of nonribosomally synthesized peptide antibiotics (gramicidin A, B, C, D, and S). Gramicidin S is the most active component; its molecular formula is C60H92N12O10 and its molecular weight is 1141.4 (Figure 83.2). It acts on the bacterial cell wall but is thought to exhibit multiple antimicrobial activities. Gramicidin is active against Gram-positive cocci, but also appears to be active against Gram-negative bacilli and fungi. Its therapeutic use is limited to topical application because it induces hemolysis.
History of cosmetic microbiology
Published in Philip A. Geis, Cosmetic Microbiology, 2006
Janet C. Curry, Daniel K. Brannan, Philip A. Geis
The 1930s also saw major microbiological advances in the medical field. The introduction of the sulfa drugs was the first advance in chemotherapy since Ehrlich’s arsenical treatment of syphilis 50 years earlier. Dubos also discovered tyrothricin, a mixture of two polypeptides — tyrocidine and gramicidin — from the Bacillus brevis soil microorganism. Tyrothricin was the first combination antibiotic produced commercially and employed clinically. Gramicidin proved to be the most useful. Dubos used it to cure his first patient, Elsie, the Borden cow, after she contracted mastitis at the 1939 World’s Fair in New York City. The 1930s represent the dawn of the antibiotic era.
Metabolomics in antimicrobial drug discovery
Published in Expert Opinion on Drug Discovery, 2022
Another strategy for reusing the known antimicrobials is to design constructs, which combine two or more pharmacophores, such as a rifamycin-quinolone hybrid drug [80], chimeric streptogramin-tyrocidine [81], a rifamycin-nitroimidazole conjugate [82], kanglemycin-fluoroquinolone hybrids [83], and a number of other hybrid constructs containing different antimicrobial pharmacophores [84]. The known antimicrobial peptides can also be improved through genetic engineering, high-throughput screening, and chemical modifications [85].
The antifungal activity of caspofungin in combination with antifungals or non-antifungals against Candida species in vitro and in clinical therapy
Published in Expert Review of Anti-infective Therapy, 2022
Shan Su, Haiying Yan, Li Min, Hongmei Wang, Xueqi Chen, Jinyi Shi, Shujuan Sun
Antimicrobial peptides (AMPs) have been investigated as a tremendous potential source of new anti-infective agents, and they are generally non toxic to mammalian cells. Polymyxins, which are produced by Paenibacillus polymyxa, are cationic cyclic heptapeptides. They can interact with the bacterial cytoplasmic membrane and therefore change its permeability and trigger cell death [78]. Caspofungin plus colistin (polymyxin E) was found to act synergistically against five caspofungin-susceptible C. albicans [79] isolates. The MIC of colistin was reduced from 50 µg/ml-250 µg/ml to 0.39 µg/ml −0.78 µg/ml, the MIC of caspofungin was reduced from 0.5–2.0 µg/ml to 0.125–0.5 µg/ml, and the FICI was 0.12–0.26. It was suggested that echinocandin-mediated alteration of the cell wall might facilitate colistin access to and perturbation of fungal membranes, which in turn would facilitate echinocandin activity [79]. The same result was found in mouse models that were infected with the wild-type strain, SC5314 [79]. Additionally, the in vitro activity of caspofungin plus polymyxin B against fluconazole-resistant C. glabrata (n = 7) was tested, and the study showed that this combination exhibited a synergistic effect against four of these strains [80]. Tyrocidine, which is produced by Bacillus aneurinolyticus, was also studied to develop antifungal drugs [81]. The tyrocidine complex exhibited a synergistic effect against biofilms with caspofungin at concentrations ranging from 1.8–6.2 µM, and the FICI was 0.10–0.35. This combination also exhibited antifungal activity in vivo; TrcA (3.0 µM) combined with CAS (0.19 µM) led to a 42 ± 3% survival rate of nematodes after five days, while CAS (0.19 µM) alone led to a 27 ± 3% survival rate [81]. The lipopeptide, PAL-Lys-Lys-NH2, in combination with CAS, showed 14 isolates with synergy and 2 indifferent isolates (87.5% and 12.5%, respectively) [82].
Acne vulgaris: new evidence in pathogenesis and future modalities of treatment
Published in Journal of Dermatological Treatment, 2021
Tyrothricin, produced by Bacillus brevis, is a polypeptide antibiotic substance consisting of two cyclic decapeptides, gramicidin S (22%) and tyrocidine A (78%). Both peptides have broad bactericidal activity against Gram-positive bacteria due to intercalation of the peptides into bacterial membranes. The efficacy and tolerability of topical tyrothricin 0.1% in acne are being evaluated (2013-001716-30) (56).