Gliotoxin is Antibacterial to Drug-resistant Piscine Pathogens

Feng, Hao; Liu, Sen; Kim, Eun La; Hong, Jongki; Jung, Jee H.

doi:10.20307/nps.2018.24.4.225

Cited by 8 publications

(16 citation statements)

References 10 publications

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“…Two less fragmented BGCs, which contained 10 / 13 genes and 7 / 13 genes, were identified in P. expansum strains d1 and MD 8, respectively. Regardless of the number of less fragmented BGCs found, to our knowledge, none of the Penicillium species in question are known to produce gliotoxin, except P. decumbens (Feng et al . 2018), suggesting that the absence of clustering in this species may be due to strain heterogeneity and requires further exploration.…”

Section: Resultsmentioning

confidence: 99%

“…In contrast, there is extensive divergence in synteny conservation among mostly fragmented BGCs (Figure 2). To our knowledge, none of the Penicillium species examined are known to produce gliotoxin, except P. decumbens (Feng et al . 2018), suggesting that the absence of clustering in this species may be due to strain heterogeneity and requires further exploration.…”

Section: Resultsmentioning

confidence: 99%

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The evolution of the gliotoxin biosynthetic gene cluster inPenicilliumfungi

Balamurugan

Steenwyk

Goldman

et al. 2023

Preprint

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Fungi biosynthesize a diversity of secondary metabolites, small organic bioactive molecules that play diverse roles in fungal ecology. Fungal secondary metabolites are often encoded by physically clustered sets of genes known as biosynthetic gene clusters (BGCs). Fungi in the genusPenicilliumproduce diverse secondary metabolites that have been both useful (e.g., the antibiotic penicillin and the cholesterol-lowering drug mevastatin) and harmful (e.g., the mycotoxin patulin and the immunosuppressant gliotoxin) to human affairs. BGCs often also encode resistance genes that confer self-protection to the secondary metabolite-producing fungus. SomePenicilliumspecies, such asPenicillium lilacinoechinulatumandPenicillium decumbens, are known to produce gliotoxin, a secondary metabolite with known immunosuppressant activity; however, an evolutionary characterization of the BGC responsible for gliotoxin biosynthesis amongPenicilliumspecies is lacking. Here, we examine the conservation of genes involved in gliotoxin biosynthesis and resistance in 35Penicilliumgenomes from 23 species. We found homologous, less fragmented gliotoxin BGCs in 12 genomes, mostly fragmented remnants of the gliotoxin BGC in 21 genomes, whereas the remaining twoPenicilliumgenomes lacked the gliotoxin BGC altogether. In contrast, we observed broad conservation of homologs of resistance genes that reside outside the BGC acrossPenicilliumgenomes. Evolutionary rate analysis revealed that BGCs with higher numbers of genes evolve slower than BGCs with few genes. Even though the gliotoxin BGC is fragmented to varying degrees in nearly all genomes examined, ancestral state reconstruction suggests that the ancestor ofPenicilliumspecies possessed the gliotoxin BGC. Our analyses suggest that genes that are part of BGCs can be retained in genomes long after the loss of secondary metabolite biosynthesis.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The evolution of the gliotoxin biosynthetic gene cluster inPenicilliumfungi

Balamurugan

Steenwyk

Goldman

et al. 2023

Preprint

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“…To date, a lot of data has been accumulated on the effect of gliotoxin on various eukaryotic cells [15]. Data on gliotoxin antimicrobial properties are accumulating [19][20][21], which allows gliotoxin to be considered in antibiotic monotherapy or in combination [18] Existing studies had shown very quickly uptake rate of gliotoxin by various mammalian cells, most of the toxin becomes cell associated within 10 min [22]. In our work we have found significant decreasing in free gliotoxin during first 10 minutes, which is consistent with the data obtained on fungi [23].…”

Section: Discussionmentioning

confidence: 99%

“…To date, a lot of data has been accumulated on the effect of gliotoxin on various eukaryotic cells [15]. Data on gliotoxin antimicrobial properties are accumulating [19–21], which allows gliotoxin to be considered in antibiotic monotherapy or in combination [18]…”

Section: Discussionmentioning

confidence: 99%

Antibacterial Action of Gliotoxin Realized Through Interaction with Tiol-containing Proteins

Vasilchenko

Gurina

Drozdov

et al. 2022

Preprint

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Gliotoxin is a secondary metabolite of various fungi belonging to the class of epipolythiodioxopiperazines. The mechanism of gliotoxin cytotoxic activity on eukaryotes is established, while the precise interaction between gliotoxin and bacteria has not been clarified yet. The aim of this study was evaluating the gliotoxin action on model Gram-positive and Gram-negative bacteria. It was found that gliotoxin uptake rate was higher in S. epidermidis than E.coli. However, for Gram-negative bacteria, the bactericidal effect is achieved at higher doses of gliotoxin (10-100 g/l), compared to Gram-positive ones (0.75-6.25 mg/l). Bactericidal effect had developed in 4 hours, which was the same for both E. coli MG1655 and S. epidermidis. Novel chip-based bioluminescent sensor with gel-immobilized E.coli MG1655 pKatG-lux revealed oxidative stress. However, pre-incubation of bacteria with Trolox did not affect the bactericidal properties of gliotoxin, while 2-merkaptoethanol and reduced glutathione significantly reduced gliotoxin`s bactericidal property. Another bioluminescent sensor E.coli MG1655 pIbpA-lux revealed heat shock stress in bacteria treated with gliotoxin. At the cellular level, exposure bacteria with gliotoxin accompanied by disruption of bacterial membranes.

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“…[ 104 ] Gliotoxin ( 71 , MIC: 0.32–0.63 µg/ml), isolated as an antibacterial metabolite of the fungus Penicillium decumbens , which was derived from the jellyfish Nemopilema nomurai , was not only active against oxytetracycline‐resistant piscine pathogens, but also demonstrated an excellent activity against MRSA and multidrug‐resistant E. faecium , and the anti‐MRSA activity was equal to that of levofloxacin (MIC: 0.32 µg/ml). [ 105 ] Compound 72 (MIC: > 256 µg/ml), isolated from the ethyl acetate extract of the culture of Neosartorya takakii KUFC 7898, was devoid of activity against the tested pathogens including MRSA. [ 106,107 ] Neofiscalin A ( 73 , MIC: 8.0 µg/ml), obtained from the marine sponge‐associated fungus Neosartorya siamensis KUFA 0017, possessed a considerable activity against MRSA and VRE, and it had no cytotoxicity against the human brain capillary endothelial cell line hCMEC/D3.…”

Section: Indole Hybridsmentioning

confidence: 99%

Recent advances in indole dimers and hybrids with antibacterial activity against methicillin‐resistant Staphylococcus aureus

Meng

Hou

Shang

et al. 2020

Archiv der Pharmazie

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Methicillin‐resistant Staphylococcus aureus (MRSA), one of the major and most dangerous pathogens in humans, is a causative agent of severe pandemic of mainly skin and soft tissue and occasionally fatal infections. Therefore, it is imperative to develop potent and novel anti‐MRSA agents. Indole derivatives could act against diverse enzymes and receptors in bacteria, occupying a salient place in the development of novel antibacterial agents. Dimerization and hybridization are common strategies to discover new drugs, and a number of indole dimers and hybrids possess potential antibacterial activity against a panel of clinically important pathogens including MRSA. Accordingly, indole dimers and hybrids are privileged scaffolds for the discovery of novel anti‐MRSA agents. This review outlines the recent development of indole dimers and hybrids with a potential activity against MRSA, covering articles published between 2010 and 2020. The structure–activity relationship and the mechanism of action are also discussed to facilitate further rational design of more effective candidates.

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Gliotoxin is Antibacterial to Drug-resistant Piscine Pathogens

Cited by 8 publications

References 10 publications

The evolution of the gliotoxin biosynthetic gene cluster inPenicilliumfungi

The evolution of the gliotoxin biosynthetic gene cluster inPenicilliumfungi

Antibacterial Action of Gliotoxin Realized Through Interaction with Tiol-containing Proteins

Recent advances in indole dimers and hybrids with antibacterial activity against methicillin‐resistant Staphylococcus aureus

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