by Tasha Phillips, M.S.
Back to Bacteria
Before we dive right into the complex world of bacterial biofilms, let’s talk about bacterial cells in general. Bacteria are free-living organisms consisting of one biological cell. They are found on every surface on the planet - including you!
There are about 30,000 varied species of bacteria that have been named and formally studied. These microscopic cells are essential to keep the life cycle moving smoothly. There are all kinds of “good” bacteria that we need! Some of those live in your gut and help with digestion and nutrient uptake.
There are also a variety of “bad” bacteria that cause illness and infection. While some bacterial species compete with one another for resources, others have learned to play nicely together to increase their chances for survival. You could think of it as sharing your cucumbers with your neighbor so they will share their tomatoes with you.
Where Do Biofilms Come From?
Among those species that have learned to live together, there are some that have learned to create biofilms. Bacterial biofilms are safe havens for cells to hide from the host immune system, antimicrobial products, and cleaning compounds.
Bacterial biofilms can consist of a single species of bacteria or several co-existing together. There are several species of bacteria that can be found in biofilms. These include Staphylococcus aureus, Proteus vulgaris, Escherichia coli, and many others. Of those types, many carry antibacterial resistance – more about that later.
Digitally colorized scanning electron microscopic image of an untreated water specimen, revealing bacteria, protozoa, and algae, within an amorphous, gelatinous biofilm mass; photo via the CDC.
How Do Biofilms Form?
Bacteria can attach themselves to biotic (alive) and abiotic (not alive) surfaces. These usually include things such as frequently-touched surfaces, surgical equipment, hospital equipment, skin wounds, and surgical sites.
There are 5 key steps in biofilm formation:
- Attachment: Bacteria encounter a surface they like.
- Cell-to-cell adhesion: Those bacteria begin to secrete substances outside of the cell (extracellular) that help them stick to one another, as well as create a ‘glue’ that adheres them to the surface.
- Proliferation: Bacterial cells begin to reproduce and grow their numbers.
- Maturation: The biofilm grows and forms inflows for nutrient intake and outflows for waste disposal. Secondary species may also enter the biofilm for nutrients and protection at this point.
- Release (Dispersion): The biofilm will release bacterial cells to find new places to attach and grow.
Escherichia coli (E. coli) biofilm, photo via the CDC
Mature biofilms are interesting in that they essentially create a little town for themselves – like Mayberry (big Andy Griffith Show fan, here). There are inflow tracts so fresh nutrients can come in and outflow tracts so waste and byproducts can be shipped out.
There is cell-to-cell signaling within the biofilm that tells others when nutrients are dense or low, what the oxygen levels are like, who can be fast growers, and who can be slow growers. The outside of the biofilm is negatively charged, allowing for positively charged bacterial cells to bind to the inside surface. The cells are then ready to be released and propagate to a new town.
Where Are Biofilms Commonly Found?
A significant percentage of the bacteria common to humans and animals can be found in the intestinal tracts. However, there is a substantial percentage that can be found on the skin (our biggest protective organ).
Most of these bacteria are harmless if the protective barrier remains intact, but we all get cuts, scrapes, abrasions, or (even more serious) surgical incisions. This is the perfect opportunity for bacteria to move in and set up shop in a moist environment with plenty of nutrients. These are called opportunistic infections.
Biofilms have been found and studied in a wide range of places, from the ocean floor to deserts to surgical equipment. They can form in extreme conditions to protect the cells inside and increase the chances for survival. We commonly find microbial biofilms in wound beds where the environment is warm and moist.
Once the protective barrier of our skin is disrupted, it creates a prime opportunity for bacterial species to take hold. While your immune system (the first line of defense against these foreign invaders) can handle most small breaks in protection, infections can and do still happen.
Unidentified bacterial biofilm on back of brown recluse spider (Loxosceles reclusa) seen at 3248x magnification and digitally colorized; photo via CDC
How Do Biofilms Contribute to Antibiotic Resistance?
This is where the fun begins! Once a bacterial species (or many) has created their own community inside this biofilm, they begin to “chat.” Just as you and I might share information about the weather, they share information about how to become resistant to antibiotics and other compounds.
Cool for them – not cool for us. There are several ways they communicate, but some of the most common are horizontal gene transfer and plasmids.
Horizontal gene transfer happens when one bacterial cell releases a small amount of genetic material containing the gene(s) for antibiotic resistance. Other bacteria in the area will suck up these floating telegrams and inject that code into their own genome. This sharing of information is crucial to cells who do not carry resistance to antibiotics.
Plasmids are much the same in that they also carry the gene(s) for antibiotic resistance. One cell can “package” these codes into a small circle of genetic material. They can then merge with a recipient cell to share this small package. The recipient cell can then, again, introduce that information into their own genome.
Once a bacterial cell has the capability to evade detection from the host, inhibit antibacterial activity, or withstand antibacterial compounds, they become much harder to eradicate from an area. This is why many times a bacterial culture (sample) is required to identify the source(s) of wound infection so that we can ensure that the correct and effective antibiotic treatment is being used. In some cases, the bacterial species have become so resistant to antibiotic treatment that curing the infection is nearly impossible.
Additionally, once a mature biofilm has been established, it can be difficult for topical antibiotics to penetrate and reach the bacterial cells - even if we do select the correct treatment. This protective layer is extremely thick, sticky, and (to be honest) smelly. So how can we treat topical infections when they have such secure armor preventing compounds from doing their job?
Staphylococcus aureus biofilm, photo via the CDC
How Does Lavengel Combat Bacteria?
First, let's talk about how antibiotics and antimicrobials typically function to eradicate infections. There are several pathways to accomplish this.
In some antibiotics, a reproductive mechanism inside the bacteria is disrupted to stop proliferation. This allows the immune system to get a handle on the infection before things get out of hand.
Others may alter nucleic acid synthesis (stop DNA rebuilding blocks), stop protein synthesis, or alter cellular membrane structures. Each of these are great ways to control bacterial replication, and therefore, stop infection from spreading. However, with each of these mechanisms, there have been sneaky bacterial species that have found a way around them.
One amazing thing about Lavengel is that it is believed to disrupt the bacterial membrane by “drilling” or “poking” into this outer membrane of the cell. This allows for Lavengel to enter in and for the things the cell needs to leak out into the surrounding area. As you can imagine, this severe stress on the membrane is more than the bacterial cell can handle, so it breaks open and dies.
The perfect analogy is getting a flat tire. The cell is the tire and the nail you just drove over is Lavengel. Once that hole is poked by Lavengel, everything the cell needs (the air) leaks out. Without the air, the tire can’t function.
Research conducted on Lavengel shows that it is not only inhibiting bacterial spread when applied before biofilms are established, but it can also penetrate pre-existing biofilms. As stated previously, these biofilms can be very thick and sticky. Without removing the biofilm prior to treatment, antibiotic drugs and compounds cannot even penetrate the surface of this glue-like armor.
This is yet another area where Lavengel can shine. Not only can it prevent infection when the wound occurs, but it can penetrate mature biofilms in untreated wounds. It is common in veterinary medicine for patients to come in with untreated skin infections - like that extra-fluffy dog that has been hiding his hot spot for who knows how long.
In the clinical setting, wounds will be cleaned thoroughly before application of any topical product. Lavengel can be applied pre-cleaning to begin working immediately as well as post-cleaning to continue clearing bacteria while also stimulating collagen formation and tissue regeneration and treating pain and inflammation in the area.
Let’s Recap
There are millions of bacteria on, in, and around us every single day. Humans and animals are subject to infection when our protective armor (our skin) is disrupted in some way. This can be scrapes, cuts, bites, surgical sites, burns – you name it.
Once the door is open, these bacteria can set up shop and start to reproduce. Many bacteria can live alongside other species underneath a protective layer called a biofilm. Once inside, they can share their own secrets (AKA genetic material) on how to fight antibiotics or the immune system.
These resistant strains can be incredibly difficult to treat both inside and outside the clinical setting. Therefore, it is important for scientists to come up with innovative ways to fight bacterial infections and stay ahead of the antibiotic resistance game.
Lavengel is a way for us to do this. Not only can it eradicate a large variety of bacterial strains before they create their own version of Mayberry, but it can also penetrate a pre-existing mature biofilm that has had the time to bulk up its sticky armor. Once applied to the area, Lavengel begins working to clear infection, stimulate new tissue growth, and lower pain and inflammation in the area.
The sooner Lavengel is applied to an area the better, but even if Fluffy hides his hot spot for a week - it’s okay, we got you!
Tasha Nelson Phillips is a veterinary assistant and researcher. She began her work in veterinary medicine in 2014 at a small practice in East Tennessee. She has a B.S. in Biology as well as a Master’s degree in Microbiology from East Tennessee State University. Her undergraduate and graduate research focused on Lavengel®, exploring its efficacy and mechanism of action against common bacterial species.
Tasha’s interests focus on natural antimicrobial options and exploring novel compounds to combat antibiotic resistance. She continues to work in small animal emergency and critical care medicine. She spends her free time with her husband and three furry babies in their East Tennessee home.