Applied Microbiology

Pharmaceutical Applications

Microbiology has been influential in the development of antibiotics, vaccines, and other critical medications.

Modern microbial biotechnology takes advantage of several characteristics of microorganisms. First, microorganisms have a high surface-area-to-volume ratio, which allows them to rapidly take up nutrients that are needed to support large quantities of biosynthesis, the production of complex molecules. Through genetic manipulation, the end products of microbial metabolic processes can be modified, and the productivity of processes can be increased. Microorganisms can also carry out a variety of enzymatic reactions. Microorganisms are able to adapt to and grow in varied environments, from the laboratory to the factory fermenter.

In 1928, Scottish scientist Alexander Fleming famously discovered the antibiotic properties of fungi, leading to the development of a wide range of modern antibiotics. An antibiotic is an antimicrobial agent used as a drug for the treatment of an infection. Since Fleming's discovery of penicillin, many other antibiotics have been discovered. After they are isolated and purified, antibiotics are refined depending on the final form that the drug will take. For example, for an antibiotic that will be part of an intravenous bag, the crystalline antibiotic is dissolved in a solution and placed in the bag, and then the bag is sealed. For topical preparations, the antibiotic is mixed with ointment. The discovery of antibiotics and the capability to produce them in large quantities have improved quality of life through the ability to successfully treat infectious disease. The capability to produce antibiotics in large quantities makes this treatment available to a wide array of people.

Microbes are a vital component in the creation of vaccines. A vaccine is a nonpathogenic substance that is used to generate a protective immune response against a particular disease. Vaccines can be attenuated or inactivated. Attenuated vaccines contain weakened forms of the pathogens that cause disease. Inactivated vaccines expose the immune system to dead or inactive antigens. The use of a vaccine triggers the synthesis, proliferation, and memory of the pathogen-fighting antibody. This process prepares the body for potential invasion by an antigen, a substance that is recognized by surface antibodies (B cells) or other immune cells to prompt an immune response. Examples of inactivated vaccines include those for pertussis and influenza, as well as the Salk vaccine for poliovirus.

Not only do vaccines protect organisms from diseases caused by microbes, but microbes can be engineered to produce vaccines. For example, the hepatitis B vaccine is produced by genetically modifying yeast cells to produce the hepatitis B surface protein that is recognized by the immune system.

Bacterial toxins can also be used in some cases to treat infection by another pathogenic microbe. One example of this includes the bacterium Serratia marcescens. S. marcescens produces a particular toxic secretory protein called type IV secretion system, or T6SS. The bacterium uses T6SS when invading host eukaryotic cells and to inhibit the growth of competing bacteria. However, recent studies have found that T6SS can be used to treat and kill invasive fungal Candida species.

Microbes are used in other pharmaceuticals beyond antibiotics and vaccines. Because bacteria have very simple genomes, they are easily manipulated to produce specific biological molecules. They also have regulatory mechanisms that can be controlled so that precise amounts of metabolites are made. A metabolite is a substance that is formed during metabolism or is required for metabolic processes. Metabolic processes in these bacteria can thus be harnessed to generate predictable quantities of substances humans need. Through the use of environmental and genetic manipulation, the production of small metabolites can be increased thousandfold. For example, the filamentous fungus Ashbya gossypii naturally overproduces the vitamin riboflavin. Scientists can further increase the amount of riboflavin produced by A. gossypii through bioengineering, which manipulates the genes responsible for making riboflavin to commercially produce even higher quantities of the substance for use in multivitamins. Bacteria can be genetically transformed to produce human metabolites in a safe and specific manner.

Before the advent of genetic engineering, pig insulin was used to treat human diabetes. This process required two tons of pig pancreas to produce eight ounces of insulin. In addition to being wasteful, there was a higher chance of an allergic reaction. Now, E. coli has been genetically engineered using recombinant DNA technology to produce human insulin. Because E. coli is small, has a doubling time of 20 minutes, and is easy to handle, the process has drastically reduced the carbon footprint, time, and expense of insulin production. Insulin is only one of dozens of pharmaceuticals approved for human use, including clotting factor, human growth hormone, and interleukin-2. In this way, bacteria are a source of important pharmaceutical products.

Production of Insulin

Human insulin can be artificially created using the bacterium Escherichia coli.