Special Issue "Marine Antibiotics"
Quicklinks
A special issue of Marine Drugs (ISSN 1660-3397).
Deadline for manuscript submissions: closed (31 October 2012)
Special Issue Editor
Guest Editor
Prof. Dr. Sergey B. Zotchev
Department of Biotechnology, Norwegian University of Science and Technology, N-7491 Trondheim, Norway
E-Mail: sergey.zotchev@nt.ntnu.no
Phone: +47 73 59 86 79
Fax: +47 73 59 12 83
Interests: streptomycetes; rare actinomycetes; antibiotics; secondary metabolite biosynthesis; engineering of biosynthetic pathways
Special Issue Information
Dear Colleagues,
Since the official discovery of the first antibiotic (penicillin), by Alexander Fleming in 1928, thousands of structurally diverse antibiotics have been reported from a variety of natural sources. Today, antibiotics continue to play the most important role in fighting various types of infections and saving millions of lives every year. However, rapid development of antibiotic resistance by bacterial and fungal pathogens, very limited supply of antiviral and antihelminthic antibiotics, and Big Pharma’s focusing mainly on chronic diseases and cancer represent a formidable challenge for anti-infective therapy of the future.
The absolute majority of currently used antibiotics have been isolated from terrestrial sources, and numerous attempts on terrestrial bioprospecting in the recent years mainly resulted in re-discovery of known antibiotics or their close analogues. Recent data strongly suggest that marine environment represents an untapped source for new biologically active molecules, in particular antibiotics. In this respect, marine bacteria and fungi seem to be the most prominent sources for antibiotic discovery due to their diversity and ability to grow rapidly and sustainably in bioreactors. Other sources, like sponges, corals and other marine animals, can also supply very interesting scaffolds for antibiotic discovery, which can be reproduced through chemical synthesis. Finally, metagenome libraries prepared from diverse marine samples and giving access to the genetic material from unculturable species may also supply new antibiotics.
This special issue of Marine Drugs is dedicated to marine antibiotics, and will be assembled to emphasize the importance of new antibiotic discovery from marine sources by various techniques and from a variety of organisms. I am very happy and honored to serve as a Guest Editor for this special issue, and would like to invite scientists to report their findings or review the recent literature on various aspects of marine antibiotics. I hope that this special issue will encourage other scientists to work on the important topic of the marine antibiotic discovery, and to report their findings in the future issues of Marine Drugs.
Prof. Dr. Sergey B. Zotchev
Guest Editor
Submission
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs is an international peer-reviewed Open Access monthly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs).
Keywords
- antibiotic
- marine organisms
- biosynthesis
- chemical synthesis
- antibiotic resistance
- antibiotic modification
- metagenome
- antiviral
- antibacterial
- antifungal
- antihelminthic
Published Papers (11 papers)
|
Received: 12 August 2010; in revised form: 25 August 2010 / Accepted: 1 September 2010 / Published: 3 September 2010
Show/Hide Abstract
| Download PDF Full-text (316 KB) | Download XML Full-text | 
Abstract: Three myxobacterial strains, designated SWB004, SWB005 and SWB006, were obtained from beach sand samples from the Pacific Ocean and the North Sea. The strains were cultivated in salt water containing media and subjected to studies to determine their taxonomic status, the presence of genes for the biosynthesis of polyketides and antibiotic production. 16S rDNA sequence analysis revealed the type strain Enhygromyxa salina SHK-1T as their closest homolog, displaying between 98% (SWB005) and 99% (SWB004 and SWB006) sequence similarity. All isolates were rod-shaped cells showing gliding motility and fruiting body formation as is known for myxobacteria. They required NaCl for growth, with an optimum concentration of around 2% [w/v]. The G + C-content of genomic DNA ranged from 63.0 to 67.3 mol%. Further, the strains were analyzed for their potential to produce polyketide-type structures. PCR amplified ketosynthase-like gene fragments from all three isolates enhances the assumption that these bacteria produce polyketides. SWB005 was shown to produce metabolites with prominent antibacterial activity, including activity towards methicillin resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE).
|
|
Received: 4 November 2010; in revised form: 1 December 2010 / Accepted: 9 December 2010 / Published: 13 December 2010
Show/Hide Abstract
| Download PDF Full-text (330 KB) | Download XML Full-text
Abstract: On a global research expedition, over 500 bacterial strains inhibitory towards pathogenic bacteria were isolated. Three hundred of the antibacterial strains were assigned to the Vibrionaceae family. The purpose of the present study was to investigate the phylogeny and bioactivity of five Vibrionaceae strains with pronounced antibacterial activity. These were identified as Vibrio coralliilyticus (two strains), V. neptunius (two strains), and Photobacterium halotolerans (one strain) on the basis of housekeeping gene sequences. The two related V. coralliilyticus and V. neptunius strains were isolated from distant oceanic regions. Chemotyping by LC-UV/MS underlined genetic relationships by showing highly similar metabolite profiles for each of the two V. coralliilyticus and V. neptunius strains, respectively, but a unique profile for P. halotolerans. Bioassay-guided fractionation identified two known antibiotics as being responsible for the antibacterial activity; andrimid (from V. coralliilyticus) and holomycin (from P. halotolerans). Despite the isolation of already known antibiotics, our findings show that marine Vibrionaceae are a resource of antibacterial compounds and may have potential for future natural product discovery.
 |
|
Received: 7 February 2011; in revised form: 24 February 2011 / Accepted: 11 March 2011 / Published: 17 March 2011
Show/Hide Abstract
| Download PDF Full-text (584 KB) | Download XML Full-text
Abstract: Marine sponge Hymeniacidon sp. was collected from coastal waters of the East China Sea to isolate symbiotic microorganisms. The resulting sponge-associated actinomycete, Streptomyces carnosus strain AZS17, was cultivated in a 20 L volume of medium for production of bioactive secondary metabolites. Bioassay-guided isolation and purification by varied chromatographic methods yielded two new compounds of kijanimicin derivatives, AS7-2 and AS9-12. Their structures were elucidated by spectroscopy and comparison with literatures. Results showed these two compounds were structurally similar to the previously reported compounds lobophorin A and B, yet differed in specific bond forms, stereochemistry and optical activities. The two novel compounds were named lobophorin C and D. In vitro cytotoxicity investigation by MTT assay indicated their selective activities. Lobophorin C displayed potent cytotoxic activity against the human liver cancer cell line 7402, while lobophorin D showed significant inhibitory effect on human breast cancer cells MDA-MB 435.
 |
|
Received: 16 December 2010; in revised form: 15 February 2011 / Accepted: 13 April 2011 / Published: 21 April 2011
Show/Hide Abstract
| Download PDF Full-text (262 KB) | Download XML Full-text
Abstract: There is an urgent need for new antibiotics to treat hospital- and community-associated methicillin-resistant Staphylococcus aureus (MRSA) infections. Previous work has indicated that both terrestrial and marine-derived members of the napyradiomycin class possess potential anti-staphylococcal activities. These compounds are unique meroterpenoids with unusual levels of halogenation. In this paper we report the evaluation of two previously described napyradiomycin derivatives, A80915A (1) and A80915B (2) produced by the marine-derived actinomycete, Streptomyces sp. strain CNQ-525, for their specific activities against contemporary and clinically relevant MRSA. Reported are studies of the in vitro kinetics of these chemical scaffolds in time-kill MRSA assays. Both napyradiomycin derivatives demonstrate potent and rapid bactericidal activity against contemporary MRSA strains. These data may help guide future development and design of analogs of the napyradiomycins that could potentially serve as useful anti-MRSA therapeutics.
|
|
Received: 5 April 2012; in revised form: 21 May 2012 / Accepted: 28 May 2012 / Published: 4 June 2012
Show/Hide Abstract
| Download PDF Full-text (365 KB) | Download XML Full-text
Abstract: Gorgonian corals possess many novel natural products that could potentially mediate coral-bacterial interactions. Since many bacteria use quorum sensing (QS) signals to facilitate colonization of host organisms, regulation of prokaryotic cell-to-cell communication may represent an important bacterial control mechanism. In the present study, we examined extracts of twelve species of Caribbean gorgonian corals, for mechanisms that regulate microbial colonization, such as antibacterial activity and QS regulatory activity. Ethanol extracts of gorgonians collected from Puerto Rico and the Florida Keys showed a range of both antibacterial and QS activities using a specific Pseudomonas aeruginosa QS reporter, sensitive to long chain AHLs and a short chain N-acylhomoserine lactones (AHL) biosensor, Chromobacterium violaceium. Overall, the gorgonian corals had higher antimicrobial activity against non-marine strains when compared to marine strains. Pseudopterogorgia americana, Pseusopterogorgia acerosa, and Pseudoplexuara flexuosa had the highest QS inhibitory effect. Interestingly, Pseudoplexuara porosa extracts stimulated QS activity with a striking 17-fold increase in signal. The stimulation of QS by P. porosa or other elements of the holobiont may encourage colonization or recruitment of specific microbial species. Overall, these results suggest the presence of novel stimulatory QS, inhibitory QS and bactericidal compounds in gorgonian corals. A better understanding of these compounds may reveal insight into coral-microbial ecology and whether a therapeutic potential exists.
 |
|
Received: 12 June 2012; in revised form: 25 July 2012 / Accepted: 1 August 2012 / Published: 15 August 2012
Show/Hide Abstract
| Download PDF Full-text (327 KB) | Download XML Full-text |
Abstract: Pseudopterosins and pseudopteroxazole are intriguing marine natural products that possess notable antimicrobial activity with a commensurate lack of cytotoxicity. New semi-synthetic pseudopteroxazoles, pseudopteroquinoxalines and pseudopterosin congeners along with simple synthetic mimics of the terpene skeleton were synthesized. In order to build structure-activity relationships, a set of 29 new and previously reported compounds was assessed for in vitro antimicrobial and cytotoxic activities. A number of congeners exhibited antimicrobial activity against a range of Gram-positive bacteria including Mycobacterium tuberculosis H37Rv, with four displaying notable antitubercular activity against both replicating and non-replicating persistent forms of M. tuberculosis. One new semi-synthetic compound, 21-((1H-imidazol-5-yl)methyl)-pseudopteroxazole (7a), was more potent than the natural products pseudopterosin and pseudopteroxazole and exhibited equipotent activity against both replicating and non-replicating persistent forms of M. tuberculosis with a near absence of in vitro cytotoxicity. Pseudopteroxazole also exhibited activity against strains of M. tuberculosis H37Rv resistant to six clinically used antibiotics.
 |
|
Received: 28 June 2012; in revised form: 26 July 2012 / Accepted: 27 July 2012 / Published: 15 August 2012
Show/Hide Abstract
| Download PDF Full-text (384 KB) | Download XML Full-text
Abstract: Some microbial species are chemically homogenous, and the same secondary metabolites are found in all strains. In contrast, we previously found that five strains of P. luteoviolacea were closely related by 16S rRNA gene sequence but produced two different antibiotic profiles. The purpose of the present study was to determine whether such bioactivity differences could be linked to genotypes allowing methods from phylogenetic analysis to aid in selection of strains for biodiscovery. Thirteen P. luteoviolacea strains divided into three chemotypes based on production of known antibiotics and four antibacterial profiles based on inhibition assays against Vibrio anguillarum and Staphylococcus aureus. To determine whether chemotype and inhibition profile are reflected by phylogenetic clustering we sequenced 16S rRNA, gyrB and recA genes. Clustering based on 16S rRNA gene sequences alone showed little correlation to chemotypes and inhibition profiles, while clustering based on concatenated 16S rRNA, gyrB, and recA gene sequences resulted in three clusters, two of which uniformly consisted of strains of identical chemotype and inhibition profile. A major time sink in natural products discovery is the effort spent rediscovering known compounds, and this study indicates that phylogeny clustering of bioactive species has the potential to be a useful dereplication tool in biodiscovery efforts.
|
|
Received: 18 October 2012; in revised form: 13 November 2012 / Accepted: 12 December 2012 / Published: 27 December 2012
Show/Hide Abstract
| Download PDF Full-text (473 KB) | Download XML Full-text
Abstract: A common limitation for the identification of novel activities from functional (meta) genomic screens is the low number of active clones detected relative to the number of clones screened. Here we demonstrate that constructing libraries with strains known to produce bioactives can greatly enhance the screening efficiency, by increasing the “hit-rate” and unmasking multiple activities from the same bacterial source.
|
|
Received: 14 November 2012; in revised form: 4 December 2012 / Accepted: 25 December 2012 / Published: 10 January 2013
Show/Hide Abstract
| Download PDF Full-text (667 KB) | Download XML Full-text |
Abstract: Polyketide 13 [=2-hydroxy-5-((6-hydroxy-4-oxo-4H-pyran-2-yl)methyl)-2- propylchroman-4-one] and three related known compounds 7, 9 and 11 were obtained and structurally characterized from Streptomyces sundarbansensis strain, an endophytic actinomycete isolated from the Algerian marine brown algae Fucus sp. Compound 13 was obtained as the major metabolite from optimized culture conditions, by using Agar state fermentation. Due to tautomeric equilibrium, 13 in CD3OD solution was able to incorporate five deuterium atoms, as deduced by NMR and ESI-MS/MS analysis. The 2-hydroxy-γ-pyrone form was established for these metabolites based on the comparison of their experimental IR spectra with the DFT calculated ones, for both the corresponding 4-hydroxy-α-pyrone and 2-hydroxy-γ-pyrone forms. During antibacterial evaluation, compound 13 stood out as the most active of the series, showing a selective activity against the gram positive pathogenic methicillin-resistant S. aureus (MRSA, MIC = 6 μΜ), with a bacteriostatic effect.
 |
Lene E. Myhren, Gyrid Nygaard, Gro Gausdal, Håvard Sletta, Knut Teigen, Kristin F. Degnes, Kolbjørn Zahlsen, Anders Brunsvik, Øystein Bruserud, Stein Ove Døskeland, Frode Selheim and Lars Herfindal
Received: 25 October 2012; in revised form: 21 December 2012 / Accepted: 4 January 2013 / Published: 30 January 2013
Show/Hide Abstract
| Download PDF Full-text (1041 KB) | Download XML Full-text
Abstract: Despite recent improvement in therapy, acute myeloid leukemia (AML) is still associated with high lethality. In the presented study, we analyzed the bioactive compound iodinin (1,6-dihydroxyphenazine 5,10-dioxide) from a marine actinomycetes bacterium for the ability to induce cell death in a range of cell types. Iodinin showed selective toxicity to AML and acute promyelocytic (APL) leukemia cells, with EC50 values for cell death up to 40 times lower for leukemia cells when compared with normal cells. Iodinin also successfully induced cell death in patient-derived leukemia cells or cell lines with features associated with poor prognostic such as FLT3 internal tandem duplications or mutated/deficient p53. The cell death had typical apoptotic morphology, and activation of apoptotic signaling proteins like caspase-3. Molecular modeling suggested that iodinin could intercalate between bases in the DNA in a way similar to the anti-cancer drug daunorubicin (DNR), causing DNA-strand breaks. Iodinin induced apoptosis in several therapy-resistant AML-patient blasts, but to a low degree in peripheral blood leukocytes, and in contrast to DNR, not in rat cardiomyoblasts. The low activity towards normal cell types that are usually affected by anti-leukemia therapy suggests that iodinin and related compounds represent promising structures in the development of anti-cancer therapy.
|
|
Received: 19 December 2012; in revised form: 22 January 2013 / Accepted: 19 February 2013 / Published: 28 March 2013
Show/Hide Abstract
| Download PDF Full-text (360 KB) | Download XML Full-text |
Abstract: Forty four marine actinomycetes of the family Microccocaceae isolated from sponges collected primarily in Florida Keys (USA) were selected from our strain collection to be studied as new sources for the production of bioactive natural products. A 16S rRNA gene based phylogenetic analysis showed that the strains are members of the genera Kocuria and Micrococcus. To assess their biosynthetic potential, the strains were PCR screened for the presence of secondary metabolite genes encoding nonribosomal synthetase (NRPS) and polyketide synthases (PKS). A small extract collection of 528 crude extracts generated from nutritional microfermentation arrays was tested for the production of bioactive secondary metabolites against clinically relevant strains (Bacillus subtilis, methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii and Candida albicans). Three independent isolates were shown to produce a new anti-MRSA bioactive compound that was identified as kocurin, a new member of the thiazolyl peptide family of antibiotics emphasizing the role of this family as a prolific resource for novel drugs.
|
Last update: 10 October 2012
