Actinobacteria and Myxobacteria—Important Resources for Novel Antibiotics 3.0

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Microbial Biotechnology".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 9623

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Working Group Microbial Strain Collection, Helmholtz Centre for Infection Research (HZI), Inhoffenstraße 7, D-38124 Braunschweig, Germany
Interests: polyphasic taxonomy; cultivation methods; isolation methods; taxonomy and secondary metabolites from Actinobacteria and Myxobacteria; morphology and fine structure of Actinobacteria and Myxobacteria
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Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of our previous Special Issues, "Actinobacteria and Myxobacteria—Important Resources for Novel Antibiotics"

https://0-www-mdpi-com.brum.beds.ac.uk/journal/microorganisms/special_issues/Actinobacteria_Myxobacteria_Antibiotics

https://0-www-mdpi-com.brum.beds.ac.uk/journal/microorganisms/special_issues/actinobacteria_myxobacteria_antibiotics_2

Bacterial infections cause millions of deaths globally, particularly in children and the elderly, and four of the 10 leading causes of death are infectious diseases in low- and middle-income countries. The continuous use of antibiotics has resulted in multiresistant bacterial strains all over the world, such as community-associated methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamases (ESBLs), and, as expected, hospitals have become breeding grounds for human-associated microorganisms, especially in critical care units.

Natural products are the bedrock and a valuable source for drug discovery programs. More than 60% of the drugs that are available on the market are derived from natural sources. Many antibiotics are made chemically via modification of natural products through a process called semisynthesis. Natural product structures have the characteristics of a high chemical diversity, biochemical specificity, and high binding affinities to their specific receptor and also interact with a wide variety of biological targets.

Microorganisms produce a wide range of natural products, which are used as lead components in the drug discovery era. Over 6000 compounds of microbial origin with antimicrobial activities have been isolated. The microbial world represents 90% of all biological diversity, and less than 1% has presently been explored (Molinari 2009). Mining microbial diversity is the key to obtaining high compound diversity, because a very large source for new natural products remains unexplored. To date, a few groups of microorganisms have been known to be high and potent producers of natural products: Actinomycetes, Bacillus, cyanobacteria, fungi, and myxobacteria.

Dr. Joachim Wink
Guest Editor

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Published Papers (3 papers)

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Research

12 pages, 1087 KiB  
Article
Miramides A–D: Identification of Detoxin-like Depsipeptides after Heterologous Expression of a Hybrid NRPS-PKS Gene Cluster from Streptomyces mirabilis Lu17588
by Constanze Paulus, Maksym Myronovskyi, Josef Zapp, Marta Rodríguez Estévez, Maria Lopatniuk, Birgit Rosenkränzer, Anja Palusczak and Andriy Luzhetskyy
Microorganisms 2022, 10(9), 1752; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10091752 - 30 Aug 2022
Cited by 2 | Viewed by 1551
Abstract
Natural products derived from plants, fungi or bacteria have been used for years in the medicine, agriculture and food industries as they exhibit a variety of beneficial properties, such as antibiotic, antifungal, anticancer, herbicidal and immunosuppressive activities. Compared to synthetic compounds, natural products [...] Read more.
Natural products derived from plants, fungi or bacteria have been used for years in the medicine, agriculture and food industries as they exhibit a variety of beneficial properties, such as antibiotic, antifungal, anticancer, herbicidal and immunosuppressive activities. Compared to synthetic compounds, natural products possess a greater chemical diversity, which is a reason why they are profitable templates for developing pharmaceutical drug candidates and ongoing research on them is inevitable. Performing heterologous expression with unknown gene clusters is the preferred method to activate gene clusters that are not expressed in the wild-type strain under laboratory conditions; thus, this method offers a way to discover new interesting metabolites. Here, we report the gene cluster assembly of a hybrid NRPS-PKS gene cluster from Streptomyces mirabilis Lu17588, which was heterologously expressed in Streptomyces albus Del14. Four new compounds were produced by the obtained strain, which were named miramides A–D. Isolation and structure elucidation revealed similarity of the isolated compounds to the known depsipeptides rimosamides/detoxins. Full article
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15 pages, 1821 KiB  
Article
Activation of a Cryptic Manumycin-Type Biosynthetic Gene Cluster of Saccharothrix espanaensis DSM44229 by Series of Genetic Manipulations
by Dominika Gorniaková, Miroslav Petříček, David Kahoun, Roman Grabic, Tomáš Zelenka, Alica Chroňáková and Kateřina Petříčková
Microorganisms 2021, 9(3), 559; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9030559 - 08 Mar 2021
Cited by 7 | Viewed by 2299
Abstract
(1) Background: Manumycins are small actinomycete polyketides with prominent cancerostatic and immunosuppressive activities via inhibition of various eukaryotic enzymes. Their overall activity towards human cells depends on the structural variability of both their polyketide chains, mainly the upper one. In our genetic screening [...] Read more.
(1) Background: Manumycins are small actinomycete polyketides with prominent cancerostatic and immunosuppressive activities via inhibition of various eukaryotic enzymes. Their overall activity towards human cells depends on the structural variability of both their polyketide chains, mainly the upper one. In our genetic screening project to find novel producers of anti-inflammatory manumycins, the strain Saccharothrix espanaensis DSM44229 was identified as containing a novel manumycin-type biosynthetic gene cluster (BGC). (2) Methods: The biosynthetic genes appeared to be silent under all assayed laboratory conditions. Several techniques were used to activate the BGC, including: (i) heterologous expression in various hosts, (ii) overexpression of putative pathway-specific regulatory genes, and (iii) overexpression of a bottleneck cyclizing aminolevulinate synthase gene in both natural and heterologous producers. (3) Results: Multiple novel manumycin-type compounds were produced at various levels by genetically-modified strains, sharing a tetraene lower chain structure with a colabomycin subgroup of manumycins, but possessing much shorter and saturated upper chains. (4) Conclusions: A cryptic manumycin-type BGC was successfully activated by genetic means to gain production of novel manumycin-type compounds for future comparative activity assays. Heterologously produced compounds were identical to those found after final activation of the BGC in the original strain, proving the intactness of the cloned BGC. Full article
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19 pages, 3559 KiB  
Article
Antimicrobial Activities of Marine Sponge-Associated Bacteria
by Yitayal S. Anteneh, Qi Yang, Melissa H. Brown and Christopher M. M. Franco
Microorganisms 2021, 9(1), 171; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9010171 - 14 Jan 2021
Cited by 21 | Viewed by 5108
Abstract
The misuse and overuse of antibiotics have led to the emergence of multidrug-resistant microorganisms, which decreases the chance of treating those infected with existing antibiotics. This resistance calls for the search of new antimicrobials from prolific producers of novel natural products including marine [...] Read more.
The misuse and overuse of antibiotics have led to the emergence of multidrug-resistant microorganisms, which decreases the chance of treating those infected with existing antibiotics. This resistance calls for the search of new antimicrobials from prolific producers of novel natural products including marine sponges. Many of the novel active compounds reported from sponges have originated from their microbial symbionts. Therefore, this study aims to screen for bioactive metabolites from bacteria isolated from sponges. Twelve sponge samples were collected from South Australian marine environments and grown on seven isolation media under four incubation conditions; a total of 1234 bacterial isolates were obtained. Of these, 169 bacteria were tested in media optimized for production of antimicrobial metabolites and screened against eleven human pathogens. Seventy bacteria were found to be active against at least one test bacterial or fungal pathogen, while 37% of the tested bacteria showed activity against Staphylococcus aureus including methicillin-resistant strains and antifungal activity was produced by 21% the isolates. A potential novel active compound was purified possessing inhibitory activity against S. aureus. Using 16S rRNA, the strain was identified as Streptomyces sp. Our study highlights that the marine sponges of South Australia are a rich source of abundant and diverse bacteria producing metabolites with antimicrobial activities against human pathogenic bacteria and fungi. Full article
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