Pinensins: The First Antifungal Lantibiotics

Mohr, Kathrin I.; Volz, Carsten; Jansen, Rolf; Wray, Victor; Hoffmann, Judith; Bernecker, Steffen; Wink, Joachim; Gerth, Klaus; Stadler, Marc; Müller, Rolf

doi:10.1002/anie.201500927

Cited by 123 publications

(119 citation statements)

References 30 publications

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“…In this trend, the number of reports concerning bacteriocins as antiprotozoal agents (20)(21)(22)(23) is surprisingly lower than that of reports aiming at other eukaryotic targets such as fungi (24)(25)(26) or even tumoral cells (27)(28)(29).…”

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confidence: 92%

Enterocin AS-48 as Evidence for the Use of Bacteriocins as New Leishmanicidal Agents

Abengózar

Cebrián

Saugar

et al. 2017

Antimicrob Agents Chemother

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We report the feasibility of enterocin AS-48, a circular cationic peptide produced by Enterococcus faecalis, as a new leishmanicidal agent. AS-48 is lethal to Leishmania promastigotes as well as to axenic and intracellular amastigotes at low micromolar concentrations, with scarce cytotoxicity to macrophages. AS-48 induced a fast bioenergetic collapse of L. donovani promastigotes but only a partial permeation of their plasma membrane with limited entrance of vital dyes, even at concentrations beyond its full lethality. Fluoresceinated AS-48 was visualized inside parasites by confocal microscopy and seen to cause mitochondrial depolarization and reactive oxygen species production. Altogether, AS-48 appeared to have a mixed leishmanicidal mechanism that includes both plasma membrane permeabilization and additional intracellular targets, with mitochondrial dysfunctionality being of special relevance. This complex leishmanicidal mechanism of AS-48 persisted even for the killing of intracellular amastigotes, as evidenced by transmission electron microscopy. We demonstrated the potentiality of AS-48 as a new and safe leishmanicidal agent, expanding the growing repertoire of eukaryotic targets for bacteriocins, and our results provide a proof of mechanism for the search of new leishmanicidal bacteriocins, whose diversity constitutes an almost endless source for new structures at moderate production cost and whose safe use on food preservation is well established.

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confidence: 92%

Enterocin AS-48 as Evidence for the Use of Bacteriocins as New Leishmanicidal Agents

Abengózar

Cebrián

Saugar

et al. 2017

Antimicrob Agents Chemother

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“…This allows RiPPs to possess a wide variety of structural features (e.g. Figure 1B) endowing them with a range of activities such as antifungal, antibacterial, allelopathic, and antiviral (Essig et al, 2014, Férir et al, 2013, Mohr et al, 2015, Zheng et al, 2015). Collectively, RiPPs represent an untapped source of chemical moieties with a vast potential to benefit society.…”

Section: Introductionmentioning

confidence: 99%

New Insights into the Biosynthetic Logic of Ribosomally Synthesized and Post-translationally Modified Peptide Natural Products

Ortega

Donk

2016

Cell Chemical Biology

249

245

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Summary Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a large group of structurally diverse natural products. Their biological activities and unique biosynthetic pathways have sparked a growing interest in RiPPs. Furthermore, the relatively low genetic complexity associated with RiPP biosynthesis makes them excellent candidates for synthetic biology applications. This review highlights recent developments in the understanding of the biosynthesis of several bacterial RiPP family members, the use of the RiPP biosynthetic machinery for generating novel macrocyclic peptides, and the implementation of tools designed to guide the discovery and characterization of novel RiPPs.

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“…The focal bacterium is closely related to Chitinophaga pinensis (Supplementary Figure 7), which was isolated originally from soil and is known for its ability to degrade chitin (Sangkhobol and Skerman, 1981). Chitinophaga pinensis also produces antibiotics with activity against a diversity of filamentous fungi (Mohr et al, 2015). That species possesses multiple genes predicted to be involved in the metabolism of carbohydrates ( n = 330) and amino acids ( n = 301; Del Rio et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

An Endohyphal Bacterium (Chitinophaga, Bacteroidetes) Alters Carbon Source Use by Fusarium keratoplasticum (F. solani Species Complex, Nectriaceae)

et al. 2017

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Bacterial endosymbionts occur in diverse fungi, including members of many lineages of Ascomycota that inhabit living plants. These endosymbiotic bacteria (endohyphal bacteria, EHB) often can be removed from living fungi by antibiotic treatment, providing an opportunity to assess their effects on functional traits of their fungal hosts. We examined the effects of an endohyphal bacterium (Chitinophaga sp., Bacteroidetes) on substrate use by its host, a seed-associated strain of the fungus Fusarium keratoplasticum, by comparing growth between naturally infected and cured fungal strains across 95 carbon sources with a Biolog® phenotypic microarray. Across the majority of substrates (62%), the strain harboring the bacterium significantly outperformed the cured strain as measured by respiration and hyphal density. These substrates included many that are important for plant- and seed-fungus interactions, such as D-trehalose, myo-inositol, and sucrose, highlighting the potential influence of EHB on the breadth and efficiency of substrate use by an important Fusarium species. Cases in which the cured strain outperformed the strain harboring the bacterium were observed in only 5% of substrates. We propose that additive or synergistic substrate use by the fungus-bacterium pair enhances fungal growth in this association. More generally, alteration of the breadth or efficiency of substrate use by dispensable EHB may change fungal niches in short timeframes, potentially shaping fungal ecology and the outcomes of fungal-host interactions.

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Pinensins: The First Antifungal Lantibiotics

Cited by 123 publications

References 30 publications

Enterocin AS-48 as Evidence for the Use of Bacteriocins as New Leishmanicidal Agents

Enterocin AS-48 as Evidence for the Use of Bacteriocins as New Leishmanicidal Agents

New Insights into the Biosynthetic Logic of Ribosomally Synthesized and Post-translationally Modified Peptide Natural Products

An Endohyphal Bacterium (Chitinophaga, Bacteroidetes) Alters Carbon Source Use by Fusarium keratoplasticum (F. solani Species Complex, Nectriaceae)

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