Antifungal membranolytic activity of the tyrocidines against filamentous plant fungi

Rautenbach, Marina; Troskie, Anscha Mari; Vosloo, J. Arnold; Dathe, Margitta

doi:10.1016/j.biochi.2016.06.008

Cited by 25 publications

(20 citation statements)

References 54 publications

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“…Because tyrocidines have been observed to interact with saccharides in the cell walls of fungal pathogens that are important in agriculture, and to provide potent antibiotic coverage for cellulose‐based dressings, our goal was to investigate the interactions of saccharides with these cyclic AMPs. Initial structures have already been obtained from the peptide dissolved in 50% ACN for NMR studies, or from crystals made from methanol solution .…”

Section: Discussionmentioning

confidence: 99%

“…The cell wall of fungi comprised predominantly of glycoproteins and polysaccharides of mainly glucan and chitin whose monomeric subunits are derived from glucose . The importance of the fungal cell wall on the antifungal activity of the tyrocidines has previously been demonstrated by Rautenbach et al Furthermore, Rautenbach and Van Rensburg have shown that the tyrocidines are readily adsorbed onto cellulose matrixes where they maintain potent antibacterial activity. The tyrocidines have been used as part of the tyrothricin complex in throat lozenges (eg, Tyrozets) containing sucrose and are safe for oral consumption .…”

Section: Introductionmentioning

confidence: 99%

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Tyrocidine A interactions with saccharides investigated by CD and NMR spectroscopies

Juhl

Rensburg

Bossis

et al. 2019

Journal of Peptide Science

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Tyrocidines are a family of cyclic decapeptides produced by the soil bacterium, Brevibacillus parabrevis. These antibiotic peptides can be used to prevent infections in agriculture and food industry but also to prepare antimicrobial lozenges, creams, and dressings for medical applications. It has been observed that the tyrocidines interact with saccharides such as cellulose from their soil environment, as well as sugars in culture media and glycans in fungal cell walls. Here, we investigated the interactions of tyrocidines with glucose, sucrose, and cellotetraose (as cellulose model) in a quantitative fashion utilising CD and NMR spectroscopy. The CD and NMR spectra of tyrocidine A (TrcA) were analysed as a function of solvent composition, and the spectral properties agree with the formation of oligomeric structures that are governed by β-sheet secondary structures once the acetonitrile content of the solvent is increased. Saccharides seem to also induce TrcA spectral changes reverting those induced by organic solvents. The CD spectral changes of TrcA in the presence of glucose agree with new ordered H-bonding, possibly β-sheet structures. The amides involved in intramolecular H-bonding remained largely unaffected by the environmental changes. In contrast, amides exposed to the exterior and/or involved in TrcA intermolecular association show the largest 1 H chemical shift changes. CD and NMR spectroscopic investigations correlated well with TrcAglucose interactions characterized by a dissociation constant around 200 μM. Interestingly, the association of cellotetraose corresponds closely to the additive effect from four glucose moieties, while a much higher dissociation constant was observed for sucrose. Similar trends to TrcA for binding to the three saccharides were observed for the analogous tyrocidines, tyrocidine B, and tyrocidine C. These results therefore indicate that the tyrocidine interactions with the glucose monosaccharide unit are fairly specific and reversible.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tyrocidine A interactions with saccharides investigated by CD and NMR spectroscopies

Juhl

Rensburg

Bossis

et al. 2019

Journal of Peptide Science

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“…How these effects are achieved and whether these observations are relevant for the in vivo situation are unknown. Studies with L. monocytogenes and the filamentous plant fungi Fusarium solani and Botrytis cinerea confirmed membrane permeabilization by tyrocidines ( 11 , 27 ). However, there is evidence that these peptides also target β-glucans in the fungal cell wall ( 27 ), suggesting that there is more to their antimicrobial activity than only membrane disruption.…”

Section: Introductionmentioning

confidence: 87%

The Multifaceted Antibacterial Mechanisms of the Pioneering Peptide Antibiotics Tyrocidine and Gramicidin S

Wenzel

Rautenbach

Vosloo

et al. 2018

mBio

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128

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Cyclic β-sheet decapeptides, such as tyrocidines and gramicidin S, were among the first antibiotics in clinical application. Although they have been used for such a long time, there is virtually no resistance to them, which has led to a renewed interest in this peptide class. Both tyrocidines and gramicidin S are thought to disrupt the bacterial membrane. However, this knowledge is mainly derived from in vitro studies, and there is surprisingly little knowledge about how these long-established antibiotics kill bacteria. Our results shed new light on the antibacterial mechanism of β-sheet peptide antibiotics and explain why they are still so effective and why there is so little resistance to them.

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“…The tyrocidines (Trc/s) are a group of cyclic decapeptides produced by Brevibacillus parabrevis in the late logarithmic growth phase (Dubos 1939;Dubos and Cattaneo 1939;Dubos and Hotchkiss 1941;Hotchkiss and Dubos 1941). The Trcs have activity against filamentous fungi (Troskie et al 2014a;Rautenbach et al 2016), yeasts (Troskie et al 2014b), Gram-positive bacteria (Spathelf and Rautenbach 2009;Leussa and Rautenbach 2014) as well as the human malaria parasite (Rautenbach et al 2007). Natural variation in the structure of these peptides results in target-specific antimicrobial activity of the different cyclodecapeptide (CDP) variants, with certain peptides being more active against fungi and others being more active against bacteria (Rautenbach et al 2007(Rautenbach et al , 2016Spathelf and Rautenbach 2009;Leussa and Rautenbach 2014;Troskie et al 2014a).…”

Section: Introductionmentioning

confidence: 99%

Modelling the variable incorporation of aromatic amino acids in the tyrocidines and analogous cyclodecapeptides

2019

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Aims A mathematical model of the nonribosomal synthesis of tyrocidines and analogues by Brevibacillus parabrevis was constructed using a competitive binding mechanism (CBM) for the incorporation of the three variable aromatic amino acid (Aaa) residues in their sequence. These antimicrobial peptides have a conserved structure (D‐Phe1‐Pro2‐Aaa3‐D‐Aaa4‐Asn5‐Gln6‐Aaa7‐Val8‐Orn9‐Leu10), apart from the Aaa in positions 3, 4 and 7 containing either Phe, Trp or Tyr. Methods and Results Ultra‐performance liquid chromatography linked mass spectrometry was used to profile peptides from extracts of cultures grown in media with various Phe : Trp ratios. The CBM model describes the production of peptides as a function of growth medium Aaa concentration. The model accounts for variable Aaa incorporation by simultaneously considering the influence of maximal incorporation rate and cooperativity, despite similar KM’s of synthetase modules. Conclusions Our CBM model can be utilized to predict the Aaa composition of produced peptides from the concentration of Aaas in the growth medium. Significance and Impact of the Study Subtly exploiting the inherent promiscuity of the nontemplate coded peptide synthesis allows for external control of peptide identity, without using genetic manipulation. Such versatility is exploitable in the production of targeted peptide complexes and rare peptides where production processes are reliant on nonribosomal synthesis.

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Antifungal membranolytic activity of the tyrocidines against filamentous plant fungi

Cited by 25 publications

References 54 publications

Tyrocidine A interactions with saccharides investigated by CD and NMR spectroscopies

Tyrocidine A interactions with saccharides investigated by CD and NMR spectroscopies

The Multifaceted Antibacterial Mechanisms of the Pioneering Peptide Antibiotics Tyrocidine and Gramicidin S

Modelling the variable incorporation of aromatic amino acids in the tyrocidines and analogous cyclodecapeptides

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