Bacteria, Biofilms, Antibiotic Resistance and Infections

Bacteria can exist as separate cells, but in nature most bacteria grow in colonies called biofilms. In a biofilm the bacteria are attached to each other and to a solid surface, and are surrounded by a protective material which they secrete. The bacteria in the film communicate and cooperate with each other. In fact, a biofilm acts almost like a multicellular organism instead of a colony of single cells.

Biofilms form in our bodies. Unfortunately, the bacteria in these films are often harder to attack with antibiotics than bacteria living outside the films, which makes some infections hard to treat.

Biofilms form in many places. They generally develop on a surface that is surrounded by liquid, such as our teeth and gums, where the film is known as dental plaque. Biofilms may also develop in other areas of the body, such as on mucosal membranes in sinuses and airways, and in wounds. In addition, they can form on metal, plastic and other artificial materials, and may develop on medical devices such as contact lenses, artificial heart valves, joint replacements, urinary catheters and dental implants. Showers and water pipes may contain biofilms, and so may drains and sewage treatment plants. Biofilms can also form on rocks in streams and aquariums.

A biofilm often has a slimy consistency and can be large enough for us to see without magnification. It may contain one species of bacteria, several bacterial species, or some mixture of bacteria, fungi, algae and other organisms.

The first step of biofilm production is the formation of a layer of material called a conditioning film on a surface. Body fluids and liquids such as pond, sewage and drain water contain polysaccharides, proteins and other substances that are quickly deposited on any new or freshly cleaned solid surface that is placed in the liquid, forming a coating. This coating, or conditioning film, provides a suitable habitat for bacteria.

Free-floating bacteria (also called planktonic bacteria) land on the conditioning film and stick to it. The bacteria have several means of adhesion. For example, some bacteria have many small projections called pilli on their cell wall, which help them stick to other bacteria and to surfaces.

The bacterial cells become surrounded by a protective material that they release, which is sticky and helps attach them to each other and to the solid surface. This material is known as EPS (Extracellular Polymeric Substance) and contains polymers such as polysaccharides, proteins and sometimes DNA. A “polymer” is a large molecule made of smaller molecules joined together. The extracellular matrix of the biofilm protects the bacteria from attack by the host’s immune system.

As new bacterial cells arrive or are made, they attach to the solid surface and/or to other bacteria, and the biofilm enlarges.

The bacteria in a biofilm release signaling molecules that affect other bacteria in a process called quorum sensing. In this process bacteria change their gene expression based on the presence of signaling molecules, also known as autoinducers, and the density of the bacterial population. "Gene expression" means that a gene becomes active, instructing the cell to make a specific substance. A signaling molecule released by one bacterium joins to a receptor on the surface of another bacterium, triggering the activity of specific genes.

When there are not many bacteria in the biofilm, there is a low level of signaling molecules in the extracellular material. As the population grows, however, the concentration of signaling molecules becomes more concentrated. There has to be a threshold level of signaling molecules present before the bacteria respond, and when they do respond, they all change their behavior at the same time and in the same way as specific genes are "turned on".

Quorum sensing is used by bacteria to coordinate activities which are more useful when done in a group rather than by a single bacterium. Examples of these activities include the production of substances which aid the attack on the host or that aid the production of the biofilm.

Numerous human diseases, especially chronic diseases, are known to be caused by bacterial biofilms. These diseases include sinusitis (inflammation of the sinus), endocarditis (inflammation of the inner layer of the heart muscle, especially around the heart valves), Legionnaire's disease, prostatitis (inflammation of the prostate gland), otitis media (inflammation of the middle ear) and a persistent lung infection by a bacterium called Pseudomonas aeruginosa that occurs in many cystic fibrosis patients.

Another problematic factor in biofilm infections is that the film has the ability to release a group of bacteria, which can then create another biofilm in a different area of the body.

The outer cells of a biofilm protect the inner cells from attack by disinfectants and antibiotics. The outer cells are more active than the inner cells. Antibiotics may be able to kill the active surface cells of the biofilm, but not the less active, non-dividing inner cells, which are often called persister cells. When the antibiotic treatment is finished, the persister cells can multiply and build up the biofilm again.

Antibiotics are effective at killing planktonic bacterial cells but are much less effective at killing biofilm bacteria. Scientists haven't known about biofilms for very long and need time to understand how the different bacteria in the film function and to create more effective medications to destroy them. The activities of bacteria in biofilms are different from those of their free-living counterparts.

Scientists are discovering that more and more bacteria form biofilms, and the list of human diseases caused by biofilm bacteria is increasing as well. Some researchers estimate that up to 80% of human microbial infections are caused by biofilms.

There is a great deal of research being done to find ways to stop the formation of biofilms or to remove them once they form. Silver compounds in bandages have shown some success in breaking up biofilms in wounds and making the bacteria inside the films more susceptible to antibiotic attack. Silver has long been known to kill planktonic bacteria. However, research is showing that a much higher concentration of silver is needed to affect biofilm bacteria. Silver coatings are sometimes applied to catheters and have reduced infections. There is some concern about the safety of high concentrations of silver inside the human body, however.

Although they can be a nuisance or dangerous to humans, researchers find bacterial biofilms very interesting to study. There is a lot to learn about the behavior of the bacteria, which is certainly more complex than we previously realized!