Can sharks, algae help win the war against superbugs?
Can sharks, algae help win the war against superbugs?
There is mounting evidence that the ability of germs to resist antibiotic treatment is growing in the U.S., with certain "nightmare bacteria" on the rise. But two antibiotic strategies from nature that have been explored by a few companies may offer alternate approaches to the problem.
Of particular concern are the so-called gram-negative bacilli (GNB) bacteria, which include E. coli, salmonella and Shigella, as well as enterobacteriaceae bacteria. Enterobacteriaceae are a family of more than 70 bacteria including Klebsiella pneumoniae and E. coli that normally live in the digestive system. Over time, some of these bacteria have become resistant to a group of antibiotics known as carbapenems, often referred to as "last-resort" antibiotics.
In March, the Centers for Disease Control and Prevention warned against carbapenem-resistant enterobacteriaceae (CRE), which spread in healthcare facilities and kill up to half of patients who get bloodstream infections from them. They have the potential to kill perfectly healthy individuals and can transfer their resistance to other bacteria within their family.
Moreover, a subsequent report by the Infectious Diseases Society of America (IDSA), published in the journal Clinical Infectious Disease, warned that the seven antibiotic drugs currently in development do not address the entire spectrum of resistance to GNBs. "We're losing ground because we are not developing new drugs in pace with superbugs' ability to develop resistance to them," said Dr. Helen Boucher, lead author of the policy paper and a member of IDSA's board of directors.
Despite the warnings, drug companies seem to be reducing their research efforts for the less profitable antibiotics in favor of cancer and cholesterol treatments. Only four pharmaceutical companies currently are involved in antibiotic research and development. One, Astra Zeneca, has announced it will reduce future investments in antibiotics; another, PolyMedix, recently announced a filing for bankruptcy.
Antibiotic drugs remain the cornerstone of the medical solution strategy, despite that technology appears to be losing the "arms race" against resistant bacteria. The number of approved antibiotics has dropped eightfold since the mid-1980s, and prospects for achieving IDSA's goal of 10 by 2020 are remote.
It should not be so surprising that we're losing this war of numbers with an organism that can spread and mutate over many quickly produced generations. A single bacterium can divide every 20 minutes, becoming 8 million cells in 24 hours The overuse and misuse of antibiotic drugs, particularly in the livestock and poultry industries, has created a vast landscape of artificial selection. The strong have survived the onslaught of our drugs and they have gone on to breed ever-stronger scions, each generation being winnowed for resistance to the drugs.
Two antibiotic strategies from nature might offer an alternate approach to this conundrum. Both come from the sea and prevent the colonization of a surface by many bacteria, but each solution is markedly different in its approach to the problem. The first is employed by the shark and the second by a common algae.
Taking a cue from a shark
Sharks are famous for their sandpaper skin. Its roughness is caused by thousands of microstructures called dermal denticles ("tiny skin teeth"). To call them bumps is to miss the elegance of their forms, for they are shaped like so many ribbed delta-wings and overlap in a precise and beautiful geometry. These denticles maintain a smooth flow of water by creating micro-vortices at each placoid scale. The micro-votices are a turbulence management system, if you will, and obviate the creation of large swirls of liquid against the shark's skin by creating many smaller swirls. Less turbulence means less drag, and therefore faster and quieter movement.
This efficiency of fluid flow appears to have an added benefit: algae and bacteria can't anchor on its skin. The micro-roughness of the surface that reduces drag also makes it inhospitable to attachment by single algae or colonies. The energy required to form a biofilm with other algae is apparently too great and they seek other, easier surfaces.
Anthony Brennan, a materials science and engineering professor at the University of Florida, was touring the Pearl Harbor shipyard when he was asked by the U.S. Office of Naval Research (ONR) to come up with a solution to the fouling of ships' hulls, a major maintenance and operational problem for the world's fleets. Brennan searched for a swimming organism that did not acquire the algae film and found the shark, specifically the Galapagos Shark. After taking a cast of the shark's skin and examining it in a scanning electron microscope, he reproduced the dimensions and proportions of the surface topography and manufactured a material that reduced green algae growth by 86 percent. ONR has funded his research since 1999.
Brennan realized that the same surface geometry could work against bacteria as well as algae and began development in 2002. In 2007, he founded the privately held company Sharklet Technologies, the first commercial antibiotic strategy based on surface structure.
The company makes films based on a microtopographical surface. It is testing the surface on urinary catheters with plans to expand into medical devices and OEM (original equipment manufacturer) of consumer products. The films are applied to high-touch surfaces such as counters, doorknobs and restroom surfaces. Sharklet claims to reduce bacterial colonization of MRSA by 86 percent, Enterococcus faecalis by 99 percent and Pseudomonas aeruginosa by 100 percent after one hour of air exposure. Each Sharklet diamond measures nearly 25 microns across (about 1/5th the thickness of a human hair) and nearly three microns deep. Each diamond contains seven ribs of varying length.
Pathogenic bacteria by Lukiyanova Natalia / frenta via Shutterstock.
Algae's biofilm defense
The common alga, Delsea pulchra, has a different approach to avoiding being covered by biofilm. It releases chemicals called furanomes that interfere with the communication between different bacteria. This communication is called "quorum signaling" because of its initiation of the grouping that eventually forms the biofilm.
Furanomes are molecules that bind to the protein-covered receptor sites on bacteria and block the reception of signaling molecules from the neighboring bacteria (N-acyl homoserine lactone).
Professors Staffan Kjelleberg and Peter Steinberg of the University of New South Wales in Sydney began research in this area in the early 1990s, and started making synthetic furamones for antifouling applications. They formed BioSignal Ltd. of Australia to also solve the boat hull antifouling challenge in 1999.
The company, between 2004 and 2010, switched to medical applications, developing treatment for contact lenses, other medical devices and the membranes on animate surfaces such as lungs. Like the Sharklet surface patterning, BioSignal's technology is a no-kill solution and avoids contributing to the artificial selection of new generations of ever more resistant germs.
The applications for the technology potentially are wide. Its products were intended as drug candidates for the treatment of lung infections, as well as oil and gas pipeline coatings, marine anti-fouling paints, water treatment, oral care products, cleaners and deodorants. BioSignal Ltd. was acquired by RGM Entertainment Pte. Ltd., in a reverse merger transaction in July 2010, after selling its biofilm intellectual property to Commonwealth Biotechnology Inc.
These two nature-based technologies demonstrate that novel solutions can be found for seemingly intractable problems like our unintentional breeding of superbugs. Both prevent the forming of biofilms, rather than the killing of the bacteria making them. One solves the problem with a precise, scale-appropriate form while the other interrupts the communication amongst the germs. To be sure, neither can substitute for effective drug development and treatment for infected patients, but it seems that bio-inspired solutions like these should be strongly considered as part of the arsenal against the coming crisis.