scholarly journals Identification of Sibling Species of the Bryozoan Bugula neritina That Produce Different Anticancer Bryostatins and Harbor Distinct Strains of the Bacterial Symbiont "Candidatus Endobugula sertula"

1999 ◽  
Vol 196 (3) ◽  
pp. 273-280 ◽  
Author(s):  
S. K. Davidson ◽  
M. G. Haygood
Keyword(s):  
Sibling Species ◽  
Bacterial Symbiont ◽  
Bugula Neritina ◽  
Endobugula Sertula

scholarly journals Evidence for the Biosynthesis of Bryostatins by the Bacterial Symbiont “Candidatus Endobugula sertula” of the BryozoanBugula neritina

2001 ◽  
Vol 67 (10) ◽  
pp. 4531-4537 ◽  
Author(s):  
S. K. Davidson ◽  
S. W. Allen ◽  
G. E. Lim ◽  
C. M. Anderson ◽  
M. G. Haygood
Keyword(s):  
Bacterial Symbiont ◽  
Type I ◽  
Bacterial Symbionts ◽  
Macrocyclic Lactones ◽  
Bugula Neritina ◽  
Heterologous Host ◽  
Genetic Potential ◽  
Full Complement ◽  
Endobugula Sertula ◽  
I Gene

ABSTRACT The marine bryozoan, Bugula neritina, is the source of the bryostatins, a family of macrocyclic lactones with anticancer activity. Bryostatins have long been suspected to be bacterial products. B. neritina harbors the uncultivated gamma proteobacterial symbiont “Candidatus Endobugula sertula.” In this work several lines of evidence are presented that show that the symbiont is the most likely source of bryostatins. Bryostatins are complex polyketides similar to bacterial secondary metabolites synthesized by modular type I polyketide synthases (PKS-I). PKS-I gene fragments were cloned from DNA extracted from the B. neritina-“E. sertula”association, and then primers specific to one of these clones, KSa, were shown to amplify the KSa gene specifically and universally from total B. neritina DNA. In addition, a KSa RNA probe was shown to bind specifically to the symbiotic bacteria located in the pallial sinus of the larvae of B. neritina and not to B. neritina cells or to other bacteria. Finally,B. neritina colonies grown in the laboratory were treated with antibiotics to reduce the numbers of bacterial symbionts. Decreased symbiont levels resulted in the reduction of the KSa signal as well as the bryostatin content. These data provide evidence that the symbiont E. sertula has the genetic potential to make bryostatins and is necessary in full complement for the host bryozoan to produce normal levels of bryostatins. This study demonstrates that it may be possible to clone bryostatin genes from B. neritina directly and use these to produce bryostatins in heterologous host bacteria.

scholarly journals “Candidatus Endobugula glebosa,” a Specific Bacterial Symbiont of the Marine Bryozoan Bugula simplex

2004 ◽  
Vol 70 (8) ◽  
pp. 4921-4929 ◽  
Author(s):  
Grace E. Lim ◽  
Margo G. Haygood
Keyword(s):  
Polyketide Synthase ◽  
Human Cancer ◽  
Taxonomic Status ◽  
Bacterial Symbiont ◽  
Gene Fragment ◽  
Bugula Neritina ◽  
Cancer Treatments ◽  
Long Rod ◽  
Endobugula Sertula

ABSTRACT The bryozoans Bugula neritina and Bugula simplex harbor bacteria in the pallial sinuses of their larvae as seen by electron microscopy. In B. neritina, the bacterial symbiont has been characterized as a gamma-proteobacterium, “Candidatus Endobugula sertula.” “Candidatus E. sertula” has been implicated as the source of the bryostatins, polyketides that provide chemical defense to the host and are also being tested for use in human cancer treatments. In this study, the bacterial symbiont in B. simplex larvae was identified by 16S rRNA-targeted PCR and sequencing as a gamma-proteobacterium closely related to and forming a monophyletic group with “Candidatus E. sertula.” In a fluorescence in situ hybridization, a 16S ribosomal DNA probe specific to the B. simplex symbiont hybridized to long rod-shaped bacteria in the pallial sinus of a B. simplex larva. The taxonomic status “Candidatus Endobugula glebosa” is proposed for the B. simplex larval symbiont. Degenerate polyketide synthase (PKS) primers amplified a gene fragment from B. simplex that closely matched a PKS gene fragment from the bryostatin PKS cluster. PCR surveys show that the symbiont and this PKS gene fragment are consistently and uniquely associated with B. simplex. Bryostatin activity assays and chemical analyses of B. simplex extracts reveal the presence of compounds similar to bryostatins. Taken together, these findings demonstrate a symbiosis in B. simplex that is similar and evolutionarily related to that in B. neritina.

scholarly journals Isolation of Two Polyketide Synthase Gene Fragments from the Uncultured Microbial Symbiont of the Marine Bryozoan Bugula neritina

2006 ◽  
Vol 72 (12) ◽  
pp. 7941-7944 ◽  
Author(s):  
Nicole B. Lopanik ◽  
Nancy M. Targett ◽  
Niels Lindquist
Keyword(s):  
Polyketide Synthase ◽  
Bugula Neritina ◽  
Microbial Symbiont ◽  
Polyketide Synthase Gene ◽  
Marine Bryozoan ◽  
Endobugula Sertula

ABSTRACT “Candidatus Endobugula sertula,” the uncultured microbial symbiont of the bryozoan Bugula neritina, produces ecologically and biomedically important polyketide metabolites called bryostatins. We isolated two gene fragments from B. neritina larvae that have high levels of similarity to polyketide synthase genes. These gene fragments are clearly associated with the symbiont and not with the host.

scholarly journals  Biologically active substances from water invertebrates: a review

2012 ◽  
Vol 57 (No. 4) ◽  
pp. 177-184 ◽  
Author(s):  
J. Sinko ◽  
J. Rajchard ◽  
Z. Balounova ◽  
L. Fikotova
Keyword(s):  
Marine Invertebrates ◽  
Soft Tissue Sarcomas ◽  
Marine Sponges ◽  
Biologically Active ◽  
Bugula Neritina ◽  
Therapeutic Benefits ◽  
Cord Injury ◽  
Anti Cancer ◽  
Fish Predators ◽  
Endobugula Sertula

Some species of invertebrates especially bryozoans (Bryozoa syn. Ectoprocta) and marine sponges (Porifera) are very important sources of pharmacologically exploitable compounds. These substances are probably produced to protect themselves from fish predators and may be an advantage in competition. The real sources of compounds with these antipredatory effects are probably not marine invertebrates themselves, but microscopic symbionts or food which they feed on. Bryostatins from bryozoan species Bugula neritina are produced by a bacterial symbiont called Candidatus Endobugula sertula. They have significant anti-cancer effects, but also other therapeutic benefits. Compounds with the structure of bryostatins were also discovered in some other invertebrates. Sponges are a source of many compounds, e.g., ara-A (vidarabine), manzamine, lasonolides, spongistatins, peloruside and others with antimicrobial, anti-cancer, immunosuppressive and similar activities. Other important sources of compounds with medical effects are tunicates (Tunicata syn. Urochordata) and some snails (Mollusca). One drug was developed from tunicates – Yondelis against refractory soft-tissue sarcomas. Certain other drugs originate from snails: e.g., prialt, which acts against chronic pain in spinal cord injury.  

scholarly journals Lack of Overt Genome Reduction in the Bryostatin-Producing Bryozoan Symbiont “Candidatus Endobugula sertula”

2016 ◽  
Vol 82 (22) ◽  
pp. 6573-6583 ◽  
Author(s):  
Ian J. Miller ◽  
Niti Vanee ◽  
Stephen S. Fong ◽  
Grace E. Lim-Fong ◽  
Jason C. Kwan
Keyword(s):  
Bugula Neritina ◽  
Shotgun Metagenomics ◽  
Content Type ◽  
Medium Components ◽  
Kinase C ◽  
Protein Kinase C Activators ◽  
Cytotoxic Compounds ◽  
Endobugula Sertula ◽  
Shed Light ◽  
Genome Degradation

ABSTRACTThe uncultured bacterial symbiont “CandidatusEndobugula sertula” is known to produce cytotoxic compounds called bryostatins, which protect the larvae of its host,Bugula neritina. The symbiont has never been successfully cultured, and it was thought that its genome might be significantly reduced. Here, we took a shotgun metagenomics and metatranscriptomics approach to assemble and characterize the genome of “Ca. Endobugula sertula.” We found that it had specific metabolic deficiencies in the biosynthesis of certain amino acids but few other signs of genome degradation, such as small size, abundant pseudogenes, and low coding density. We also identified homologs to genes associated with insect pathogenesis in other gammaproteobacteria, and these genes may be involved in host-symbiont interactions and vertical transmission. Metatranscriptomics revealed that these genes were highly expressed in a reproductive host, along withbrygenes for the biosynthesis of bryostatins. We identified two new putativebrygenes fragmented from the mainbryoperon, accounting for previously missing enzymatic functions in the pathway. We also determined that a gene previously assigned to the pathway,bryS, is not expressed in reproductive tissue, suggesting that it is not involved in the production of bryostatins. Our findings suggest that “Ca. Endobugula sertula” may be able to live outside the host if its metabolic deficiencies are alleviated by medium components, which is consistent with recent findings that it may be possible for “Ca. Endobugula sertula” to be transmitted horizontally.IMPORTANCEThe bryostatins are potent protein kinase C activators that have been evaluated in clinical trials for a number of indications, including cancer and Alzheimer's disease. There is, therefore, considerable interest in securing a renewable supply of these compounds, which is currently only possible through aquaculture ofBugula neritinaand total chemical synthesis. However, these approaches are labor-intensive and low-yielding and thus preclude the use of bryostatins as a viable therapeutic agent. Our genome assembly and transcriptome analysis for “Ca. Endobugula sertula” shed light on the metabolism of this symbiont, potentially aiding isolation and culturing efforts. Our identification of additionalbrygenes may also facilitate efforts to express the complete pathway heterologously.

scholarly journals Latitudinal Variation of a Defensive Symbiosis in the Bugula neritina (Bryozoa) Sibling Species Complex

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e108783 ◽  
Author(s):  
Jonathan Linneman ◽  
Darcy Paulus ◽  
Grace Lim-Fong ◽  
Nicole B. Lopanik
Keyword(s):  
Sibling Species ◽  
Species Complex ◽  
Latitudinal Variation ◽  
Bugula Neritina ◽  
Defensive Symbiosis

A Simplified Placenta-Like Brooding System in Bulgula neritina (Bryozoa)

1972 ◽  
Vol 30 ◽  
pp. 130-131 ◽  
Author(s):  
Robert M. Woollacott ◽  
Russel L. Zimmer
Keyword(s):  
Bugula Neritina ◽  
Brood Chamber ◽  
Tissue Mass ◽  
Embryonic Nutrition

Embryos of many bryozoans are retained during development within a helmetshaped brood chamber that is composed of two parts: an outer, double-walled, calcified ooecial fold and an inner, membranous ooecial vesicle. The embryo is brooded “externally” between these two structures and, in Bugula neritina, increases 27 to 35 fold in volume during its embryogenesis. Since the blastocoelic space is obliterated early in development, this change represents an increase in tissue mass. Clearly, some form of extra-embryonic nutrition is implicated. Calvet first noted that the lining of the ooecial vesicle in regions adjacent to the embryo undergoes a pronounced hypertrophy, and Marcus later proposed that this epithelium provides nutrition to the young. Sileh, however, suggested that the hypertrophied layer functions only as a supportive cushion.

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