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