Marine Pharmaceuticals: Seaweed, Sinusitis, and the Stunning Biodiversity of our Oceans

by Mary Hall on February 28, 2013

Any three-year old can tell you what seaweed and boogers have in common.  But who could have imagined that the cure for sinusitis lay on seaweed’s slippery surface?

Apparently, not the scientists who discovered the cure.  They were marine scientists who were studying seaweed while looking for a way to safely remove barnacles from the surfaces of ships.  While marine scientists were focusing on barnacles, medical experts were resorting to surgery to remove chronic bacterial infections from the surfaces of our sinuses.

In hindsight, it seems obvious that their paths would cross.  But we’re getting ahead of our story.

How a group of marine scientists stumbled upon a cure for chronic sinusitis—using seaweed.

Illustration by Samuel Hall

 

Barnacles

Scientists at Newcastle University in the United Kingdom discovered something interesting in the slime covering the surface of seaweed.  It’s an enzyme, called NucB, from a common marine bacterium, Bacillus licheniformis.  An enzyme is a protein that starts or speeds up a specific chemical reaction.  The scientists were hoping this enzyme could attack the “cement” that barnacles use to cling to ships.  To understand how an enzyme might do this, you need to know a little about biofilms—a subject that is generating a lot of excitement in microbiology, medicine, and public health.

Biofilms

Try to visualize hundreds of those common marine bacteria, Bacillus licheniformi.  Now zoom in.  Do you visualize the individual bacteria moving about independently within the larger group?  If you do, you’re not alone.  The popular image of bacteria consists of free organisms or “loners.”   Nothing could be further from the truth.  Scientists now know that 99.9 percent of all bacteria live in a community and attach to surfaces as cohesive layers known as biofilms.

Why would a single bacterium join a biofilmThree words: strength in numbers.  A biofilm is a highly protective layer of bacteria. It begins from a single bacterial cell and comes together to form structures with three defining characteristics:  (1) an ability to bind strongly to a surface, (2) an extracellular protective matrix, and (3) communication between cells by “quorum sensing.”  That last characteristic is a form of decision-making that is communicated throughout the biofilm.  Scientists discovered “quorum sensing” while they were observing bioluminescence in the ocean. Under certain conditions, a critical number of biofilm bacteria sense –and then communicate to the wider group –that it is worth expending the energy to “light up” as a form of collective protection.

Copyright: Doug Perrine

Quorum sensing may also be used to maintain the biofilm’s protective matrix, which is like a community suit of armor that resists enemy invasion.   The matrix consists of polymers, small amounts of protein, and DNA, which plays a key role in binding the components together. Without this structure, the bacterial mass would merely be a loosely organized colony (not a protective biofilm) and, as such, be vulnerable to attack by things that go about killing innocent bacteria.

By now you may have guessed that a barnacle’s “cement” is a form of biofilm. 

Occasionally, a few brave bacteria decide to leave the security of the group.   Newcastle University scientists discovered that when the marine bacteria Bacillus licheniformis want to leave their slimy seaweed biofilm, they release the enzyme, NucB, which breaks down the external DNA, causing the biofilm to break apart and free the bacteria from the matrix.  The scientists isolated NucB from the seaweed slime, purified it, and tested it on other types of biofilms. One of the biofilms tested was the “cement” used by barnacles.  And, yes, NucB caused this cement to break apart. As a result, the stubborn barnacles finally lost their grip.

“80% of all infections in humans are related to biofilms.”

                                                U.S. National Institutes of Health

When the marine scientists presented a lecture on their NucB-barnacle success, a sinusitis patient happened to be in the audience.  He mentioned NucB to his doctor, a medical researcher specializing in chronic sinusitis (commonly known as a chronic sinus infection).   Normally, mucus collects in the sinuses and drains into the nasal passages. With sinusitis, the sinuses become inflamed, unable to drain, and then infected.  Sinusitis bacteria create a biofilm.  Compared to lone bacteria, bacteria within biofilms are up to 1,000 times more resistant to antibiotics.  As a result, once a biofilm forms, surgery is often the only effective treatment.

That is, until now.

Marine scientists and surgeons from Newcastle University are currently developing a nasal spray that uses the enzyme NucB to help clear chronic sinusitis.  When tested on biofilms from 24 different strains of sinusitis bacteria, NucB broke through and dispersed 58 percent of them.  Once these biofilms are dispersed, the released bacteria are helpless against the very antibiotics they once repelled as a group.

Finding Our Cures in the Ocean

Was this a fluke?  Finding a cure for sinusitis in seaweed?

Hardly.

In the past, more than half of our medical drugs have been either extracted from natural sources or synthesized using natural products.  According to the National Research Council (NRC), drug discovery research is now turning to the ocean because of its relatively unexplored biodiversity compared to land environments.  Considering microbes alone, most of the Earth’s microbial diversity is found in the ocean. The NRC suggests that ocean bacteria could constitute as much as 10% of the total living biomass carbon in the biosphere. A relatively small number of these species have been studied to date.  Still, from these few species, thousands of chemical compounds have been isolated.

REFERENCES

Hunter P. 2008. The mob response.  European Molecular Biology Organization (EMBO) Reports. 9(4): 314-317. doi:10.1038/embor.2008.43

National Institutes of Health (NIH) and Department of Health and Human Services. Immunology of biofilms. Program Announcement (PA) Number: PA-07-288.  http://grants.nih.gov/grants/guide/pa-files/PA-07-288.html

National Research Council. Marine derived pharmaceuticals and related bioactive ingredients. Chapter 4 in Monsoons to Microbes: Understanding the Ocean’s Role in Human Health. Washington, DC: The National Academies Press, 1999.  http://www.nap.edu/catalog.php?record_id=6368

Sanders R. 2012. Discovery opens door to attacking biofilms that cause chronic infections. Press Release. University of California at Berkeley.   http://newscenter.berkeley.edu/2012/07/12/discovery-opens-door-to-attacking-biofilms-that-cause-chronic-infections/

Shields RC, Mokhtar N, Ford M, Hall MJ, Burgess JG, et al. 2013. Efficacy of a marine bacterial nuclease against biofilm forming microorganisms isolated from chronic rhinosinusitis. PLoS ONE 8(2): e55339. doi:10.1371/journal.pone.0055339

Bidewell K. 2013. A solution to sinusitis from the sea. Press Release. University of Newcastle. http://www.ncl.ac.uk/press.office/press.release/item/a-solution-to-sinusitis-from-the-sea

 

David Reedy March 1, 2013 at 7:04 am

Fascinating and well written.

Mary Hall March 1, 2013 at 9:40 am

Thank you David!

Brian Zikmund-Fisher March 1, 2013 at 8:22 am

Agreed. Really interesting connection between biofilms (something few of us think about) and an everyday medical problem.

Nice job.
Brian

Mary Hall March 1, 2013 at 9:42 am

Thank you. You made my day!
Mary

Loon March 1, 2013 at 1:11 pm

Interesting and well written article. I was just thinking… if this enzyme breaks apart many biofilms, and 80% of our infections are related to biofilms, there might be more than the cure for chronic sinusitis around the corner…

Mary Hall March 1, 2013 at 5:02 pm

I had the same impression. This area of biofilms and enzymes seems really promising. One thing to remember though — it takes a very long time for pharmaceuticals to go through all the necessary trials and then obtain FDA approval. So NucB has a few more hurdles to clear before it can be marketed. We still have to find out if there are adverse effects . . .

Thank you for reading and contributing!

Virginia March 1, 2013 at 11:17 pm

I knew this would a good read when the first sentence was read. Truly a good attention hook. As you observe there are high hopes in discovering more medical”miracles” in the oceans. Extreme pollution taking place in our oceans will be a deterrent to the finds comparable to the destruction of the rainforest I fear.
Thank you for this exciting research.

Mary Hall March 2, 2013 at 11:00 am

Virginia,
Thank you for sharing your thoughts–especially your point about the health of our oceans being an important concern. Originally, I had planned to use the “seaweed research story” as a jumping off point to discuss the larger story of the oceans –how much they have to offer in terms of marine pharmaceuticals and how global warming and pollution are destroying so much of that potential.
As I researched my article and, in particular, read about “biofilms,” I realized that the news coming out of biofilms research is really exciting. I got a glimpse into the scientists’ joy of discovery and the wider sense of wonder that drives pure research. It was uplifting and I wanted to share this sense of excitement with everyone. For that reason, I decided to end my story on a positive note. Unfortunately, I sacrificed the bigger more poignant story of how we are losing research opportunities as we continue to destroy the oceans’ biodiversity.
I love your thoughtful comments. Thanks for reading!
Mary

billc108 March 27, 2013 at 11:04 pm

Mary, don’t stress too much about the change of focus from “save the oceans” to “hey, look at this, another cool thing we just learned about from studying the oceans”. You’re adding another good reason to our arsenal. Intelligent people can make the connections themselves, especially if you give them good information and a proper nudge in the right direction, both of which you did.

People are better able to grasp the significance of smaller, more human sized problems (lots of people can relate to sinusitis) than huge, daunting problems like “save the oceans” or climate change. Get enough of those human size solutions together and it’s easier to see how it’s all interconnected.

Mary Ellen Anderson March 2, 2013 at 6:08 pm

Fascinating article. Presently consuming antibiotics for a sinus infection, I look forward to a much better solution. Thanks for your report.

Mary Hall March 4, 2013 at 4:43 pm

I hope you feel better soon. Thanks for your comment!

Angela March 3, 2013 at 8:38 pm

Thanks for the post. The connection between the two research areas is fascinating! I feel like reading more about ocean based bacteria :)

Mary Hall March 4, 2013 at 4:44 pm

Thanks for reading my post!

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