Draft:Antibiotic resistance in actinobacteria

Actinobacteria are a group of gram-positive bacteria that have a unique behavior associated with them: the creation of biofilms. Biofilms are communities of microorganisms that penetrate surfaces and produce a certain type of susbstance known as extracellular polymeric substances (EPS). Biofilms can be found in many different kinds of environments including soil, water, and the human body, where they can cause potentially severe infections and diseases. Certain types of actinobacteria have been shown to be resistant against antibiotics, creating health scares for certain groups of people.

Mycobacterium biofilms
One kind of actinobacteria that is well-known for its ability to form biofilms is Mycobacterium. Mycobacterium is a genus of acid-fast bacteria that includes several other species such as Mycobacterium tuberculosis and Mycobacterium leprae. As mentioned in the name, Mycobacterium tuberculosis can cause tuberculosis, a particularly violent and severe disease, and Mycobacterium leprae can cause leprosy.

The biofilms that are formed by these Mycobacterium are especially difficult to treat with antibiotics because they are highly resistant to penetration. This means that it is very difficult to breach the biofilms and therefore the antibiotics cannot have the desired effect to eliminate the bacteria. This resistance is due to a variety of factors including the EPS matrix that surrounds and protects the biofilm, the slow and progressive growth rate of bacteria within the biofilm itself, and the presence of persister cells.

EPS matrix
The first key element that leads to the resistance against the antibiotics is the presence of the EPS matrix. The EPS matrix provides structural support and protects the bacteria from any outside influences such as the antibiotics. The EPS matrix can be seen as a wall that is protecting and shielding the bacteria from any environmental and external dangers. This matrix is primarily made up of various polysaccharides, proteins, and lipids that act as the physical barrier preventing penetration of the biofilm. Furthermore, this matrix also has the ability to isolate the antibiotics and prevent them from having access to the bacteria within the biofilm. This matrix is an important aspect of the protection that the bacteria receives against the threat of antibiotics.

Slow growth rate
Another aspect of the resistance against the antibiotics targeting the bacteria is the fact that the bacteria within the biofilm have a slow growth rate. Antibiotics are usually designed to target actively growing cells or cells that create an immediate danger or threat. Slow-growing cells would not meet this criteria as they are in more of a dormant state and do not trigger any warning signs. This means that it is more likely for the bacteria to not be targeted by the antibiotics and be able to grow and replicate within the confines of the biofilm. In addition, antibiotics are designed to target specific cellular processes such as cell synthesis or cell division. These cellular processes are normally only active during sustained periods of rapid growth, criteria that the bacteria in Mycobacterium biofilms do not meet.

Persister cells
The final factor that contributes to the ability of Mycobacterium to resist antibiotics is the continued presence of persister cells. These cells are a population of bacteria within the biofilm that are highly tolerant to antibiotics and in a mostly dormant state. These cells can withstand antibiotic treatment and continue to penetrate surfaces and create more severe diseases and infections in some individuals. In general, persister cells have adapted to be sable to resist antibiotic treatment by entering a dormant state and pretending to not be active or in an active state of growth or use, therefore not triggering any warning signs in the antibiotic. These cells are the main catalyst for the continued presence of diseases and infections due to Mycobacterium as a result of the ineffectiveness of the antibiotics to eliminate them.

Clinical risks
The combination of these three factors make Mycobacterium biofilms extremely difficult to penetrate and very resistant to antibiotic treatment. This has many real clinical implications as Mycobacterium infections can be very serious and if left untreated, can grow more severe with time. These infections can potentially even lead to chronic disease. Treatment options are difficult to find as many of the common medical practices to treat bacterial infections and diseases, including using antibiotics or specifically targeting the infected area, do not work on Mycobacterium biofilms due to the acquired resistance to antibiotics and the presence of the EPS matrix, making the biofilm very difficult to penetrate.

New approaches and solutions
New approaches are being researched and developed to come up with a solution of how to treat these Mycobacterium biofilms. One promising idea is to directly target the EPS matrix that encloses and shields the biofilm. This strategy would use enzymes acting as catalysts to break down the matrix or use other chemical agents to change the physical shape of the matrix, making the matrix more permeable and easier to access.

Another potential strategy is to directly target the persister cells as they are the root of the problem and the reason why Mycobacterium is resistant to antibiotics. This would involve the development of drugs that would influence the state of the persister cells and prevent them from being dormant when in the presence of antibiotics. In addition, persister cells could be manipulated and tricked into being triggered and becoming active when in the presence of antibiotics through the use of outside agents and chemicals.