A biofilm is a very clever way a microorganism can protect itself and survive in humans and on surfaces. Using a unique communication system, called quorum sensing, microorganisms are able to adhere to a surface whether it is alive or non-living. They create architectural colonies and an environment where they expand in numbers, mature and release whist resisting detection from the human immune system and antimicrobials. Bioflims often occur in hospital-type setting and in cases of chronic non-resolving infections.
What is a biofilm?
A biofilm is a structural community of micro-organisms, such as fungi and bacteria, residing in an expansive, self-produced extracellular matrix. It is a molecular structure consisting mostly or entirely of similar units bonded together (a polymeric substance).
The Extracellular polymeric substance (EPS) produced by the collection of microorganisms forms during the attachment stage and can irreversible adhere to surfaces unless quickly removed. It is made mainly of protein, polysaccharides, DNA, RNA, ions, and water.
Water flows through voids created within the 3D structure of the EPS creating a circulatory system delivering nutrients and removing waste products from the micro communities residing within. Important minerals and nutrients are scavenged by the EPS from the surrounding environment.
An exopolysaccharide matrix provides strength to the interaction of the microorganisms. This matrix is a highly complex mix of fibrous proteins, glycoproteins and proteoglycans forming a non-cellular component.
Biofilm development
The development of a biofilm involves many complex steps which basically start with attachment and formation and end with detachment.
Attachment
Beginning with quorum signalling between cells, the microorganism attach to living or non-living surfaces using appendage which resemble pili or flagella, or through other physical means. Adherance is more likely to occur with hydrophobic (water-repelling) surfaces like Teflon and plastic as a opposed to hydrophilic (water-loving) surfaces such glass and metal.
Formation
Once the microbes have become securely attached the process of growth begins. Communicating using quorum sensing within the EPS, the next step is multiplication and division. The result is the formation of many types of micro communities which depend on and coordinate with one another for the utilization of substances for energy and survival.
- Quorum sensing refers to cell-to-cell communication and allows bacteria to coordinate their activities. Communication is dependent on the production and release of small signal molecules and, as the bacterial population increases, so does the concentration of signal molecules. This regulation allows bacteria to control gene expression in response to population density. Quorum sensing allows the bacterial population to work together to improve nutrition, its defences against rivals and its ability to survive conditions not necessarily conducive to its existence. Gram-negative, gram-positive bacteria and fungi use quorum sensing techniques.
Detachment
Once multiplication has occurred the microbial cells convert from being sessile (fixed in one place) to a motile form and detach into the environment to create new areas of colonizaton. They do this by their own force or from a physical stress with the help of different saccharolytic enzymes.
Detachment of microbial cells results in the spread of infection.
Infection associated with a biofilm
Surgical implants such as joint prothesis, breast implants, mechanical heart valves, ventricular shunts, pacemakers, ventricular-assisted devices and voice protheses; and devices like contact lenses and catheters are some examples of non-living surfaces which can host a biofilm.
In the body potential pathogenic infection using biofilms is wide-spread. Examples include:
- Periodontitis (infection of the gum). Halitosis may be due to a biofilm
- Osteomyelitis (bone disease)
- Otitis media (ear infections)
- Skin ulcers
- Chronic infections or non-resolving infections - such as rhinosinusitis and urinary tract infections (UTI's)
- Acne
- Ingrown toenails
Breaking through the biofilm
The formation of bacterial biofilm is a major concern in the treatment of disease as they are extremely resistant to antibiotic and antimicrobial therapies. Many chronic infections are due to a bacterial biofilm and in many cases, the only resolution is to surgically remove the biofilm, along with the implant, organ or tissue it has infected.
The EPS matrix of the biofilm plays a major role in resistant mechanisms to antibiotic therapy, preventing or delaying antimicrobials from interacting with microbes. In some instances, some components of antimicrobials may even support matrix synthesis.
Finding ways of breaking through the barrier to inhibit or interfere with the EPS matrix may take a combination of different strategies. Some important research has shown positive result using the following:
Antimicrobial peptides (AMPs). These are a diverse class of naturally occurring molecules which are produced as a first line of defence of the innate immune system. They offer a promising approach in the treatment of biofilm-associated infections. AMPs can kill (bactericidal effect) or at least cause interference with the lifestyle of the biofilm.
- Biofilm formation is not just a concern for the operating theatre and the human body, it can also present as a problem to our food production industry. One example is the dairy industry where colony-forming bacteria can adhere to the surfaces of equipment putting to risk the safety and quality of the milk and by-products. Using a peptide-based coating was found to modify the physical properties of the stainless-steel surface of equipment and reduced its availability for bacterial adhesion, without any adverse effect to the milk.
Acetyl acid. The nondissociated molecule of acetyl acid was shown to eradicate mature biofilms.
Manuka Honey
This is a specific honey produced by nectar obtained from the manuka tree Leptospermum scoparium. It offers a broad-spectrum antimicrobial activity with low antibacterial resistance. In studies manuka honey has shown an ability to prevent and eradicate biofilms produced by common wound pathogens.
Colloidal silver has shown in studies to have significant antibiofilm activity in vitro and in vivo against S. aureus, MRSA, and P. aeruginosa.
N-acetylcysteine is a mucolytic agent which may interfere with exopolysaccharide formation in biofilms and inhibit S. epidermidis biofilm formation.
Essential oils. Many medicinal essential oil have been shown to have an antibacterial and inhibitory action towards bioflim formation. Some examples include:
- Origanum majorana, Thymus zygis and Rosmarinus officinalis showed antibacterial and biofilm inhibitory action towards Escherichia coli in patients suffering from Urinary tract infections (UTIs).
- Oregano vulgaris as a nanoemulsion has been shown to be a potent and effective alternative for treating acne.
- Garlic oil can disrupt the quorum sensing pathways of the opportunistic pathogen Pseudomonas aeruginosa.
Herbal medicine
Chinese Skullcap (Scutellaria baicalensis) shown to inhibit the formation of Pseudomonas aeruginosa biofilms and enhance the bactericidal effects of various conventional antibiotics in vitro. It has also been shown to be effective against for Staphylococcus aureus and had activity against MSSA and MRSA
Licorice (Glycyrrhiza glabra) has shown activity against Streptococcus faecalis.
Many of these studies have been performed based on a specific disease or bacteria and may also be useful in the fight against biofilm formation of other microorgansms in other areas of the body.
Good hygiene conditions and practices. Preventing biofilm adhesion on common surfaces often depends on the material used and much research is being done in this area. Good hygiene practices of regularly wiping down surfaces with soap and water, including hands, is often the first step in reducing microbial load and reduce the ability of a biofilm to adhere.
References
- Bacterial biofilm and associated infections https://www.sciencedirect.com/science/article/pii/S1726490117302587
- https://www.sciencedirect.com/topics/medicine-and-dentistry/quorum-sensing
- https://www.sciencedirect.com/topics/medicine-and-dentistry/exopolysaccharide
- Antimicrobial peptides and their interaction with biofilms of medically relevant bacteria☆
- Antibiofilm Properties of Acetic Acid https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486441/#
- Antimicrobial peptides https://www.sciencedirect.com/science/article/pii/S0960982215014098
- Preventing Biofilm Formation by Dairy-Associated Bacteria Using Peptide-Coated Surfaces https://www.frontiersin.org/articles/10.3389/fmicb.2019.01405/full
- Honey can inhibit and eliminate biofilms produced by Pseudomonas aeruginosa https://pubmed.ncbi.nlm.nih.gov/31796774/
- Manuka honey sinus irrigation for the treatment of chronic rhinosinusitis: a randomized controlled trial https://pubmed.ncbi.nlm.nih.gov/27935259/
- Antimicrobial effects of Manuka honey on in vitro biofilm formation by Clostridium difficile https://pubmed.ncbi.nlm.nih.gov/28417271/
- Topical Colloidal Silver for the Treatment of Recalcitrant Chronic Rhinosinusitis https://pubmed.ncbi.nlm.nih.gov/29696011/
- Antibacterial and Biofilm Inhibitory Activity of Medicinal Plant Essential Oils Against Escherichia coli Isolated from UTI Patients https://pubmed.ncbi.nlm.nih.gov/30909573/
- Origanum vulgare L. Essential Oil as a Potential Anti-Acne Topical Nanoemulsion-In Vitro and In Vivo Study https://pubmed.ncbi.nlm.nih.gov/30154336/
- Diallyl disulfide from garlic oil inhibits Pseudomonas aeruginosa virulence factors by inactivating key quorum sensing genes https://pubmed.ncbi.nlm.nih.gov/29951860/
- Antimicrobial and Biofilm Effects of Herbs Used in Traditional Chinese Medicine https://journals.sagepub.com/doi/pdf/10.1177/1934578X1300801129#
- Baicalin inhibits biofilm formation, attenuates the quorum sensing-controlled virulence and enhances Pseudomonas aeruginosa clearance in a mouse peritoneal implant infection model https://pubmed.ncbi.nlm.nih.gov/28453568/
- Novel Strategies for the Prevention and Treatment of Biofilm Related Infections https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794791/
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