For the past few decades, a critical topic of discussion has been the growing public health crisis around bacterial resistance which continues to increase exponentially. This crisis has many health organizations launching national campaigns to target awareness and increase efforts to find a viable solution by educating physicians, healthcare providers, consumers, and employers about appropriate antibiotic usage.

While antibiotics are an essential part of modern medicine and with more than 150 different antibiotics available in the market today, the prevalent misuse of these drugs has led to serious problems, such as bacterial resistance to antibiotics. Physicians over-prescribing antibiotics, improper dosage, patient misuse of the drug, and mutations in bacteria can create antibiotic resistance that makes it increasingly difficult to treat potentially life-threatening illnesses. Long-term use of antibiotics can also result in the disruption of normal bodily functions and can make a person more susceptible to disease causing bacteria and infections. Proper infection prevention and control are essential factors that can assist in saving antibiotic strength.

The healthcare industry as a whole has a responsibility to change the attitude of physicians and consumers toward proper antibiotic utilization. A logical method of prevention would be to practice diligence with measuring the amount of antibiotics currently prescribed to patients. With this crisis on the rise, it has become imperative to save antibiotic strength to preserve its potency and effectively treat the conditions for which they were originally created.

In our pursuit to find solutions to address this concern, Heritage Medical Research Institute (HMRI) turns to California Institute of Technology’s (Caltech) scientists and engineers – our “HMRI Investigators” who specialize in multidisciplinary science and technology to discover new methods to fight diseases while progressively driving innovation forward to improve the human condition. One of HMRI’s Investigators at Caltech, Sarah E. Reisman, Ph.D., Professor of Chemistry and the Executive Officer for Chemistry at Caltech, is on the cutting-edge of studying antibiotic compounds to combat bacterial resistance.

Professor Reisman specializes in organic chemistry and the development and study of total synthesis found in natural products. Half of the chemicals used today are found in nature. The complexity of re-engineering the structure of compounds and their unique relationship and interaction to each other, to mitigate drug-resistant drugs, is key to identifying the process of making them modular; or as she explains, “creating the building blocks, or Lego-science” approach to find a more viable solution.

While engineers and scientists in their respective fields are conducting parallel studies, most are not working on the same class of the compound being studied at Caltech. Their novel approach is exclusive with respect to testing a particular molecule class. The idea is rather than trying to build up a synthetic and take a molecule that has been isolated from a compound that has combative properties, they must first figure out how to make that compound and change the way they can remodel that structure.

The average lifecycle from creating the molecular compounds, testing its viability to final verification takes approximately a year and a half – more or less. The most effective method is to test as many molecules at a given time; test them as they are being built. The modular approach is to make a few at a time so that they can swap out one for the other to avoid the step of having to start from the beginning if the particular molecule’s outcome is unsuccessful. This process requires setting up a screen of bacteria with known resistant properties to analyze them to determine each structure’s function. The goal is to be able to create compounds based on the existing structures to achieve remodeling compound products that convert good antibiotics to even better and more effective ones.

Professor Reisman is confident that they have reached a point where they can successfully remodel compounds. While the application of this “Lego” analogy to design cutting-edge molecules is one that the scientific community has yet to figure out, Professor Reisman and her team have made significant progress with this first step and have a solid plan in place to move forward in presenting solutions to preserve antibiotic strength. Their optimistic endeavors are to discover a significant breakthrough within the next few years.

She adds, “My hope is that if our findings follow the current pathway, we will be able to continue to make a series of compounds to map out the antibiotic properties. There is some interesting study on compound modification where you can make compounds that are effective against gram-positive bacteria as well as gram-negative bacteria. If we can figure out the structure of pleuromutilin and turn it into an antibiotic for gram-negative – which is a very challenging process given that far fewer antibiotics are effective against gram-negative than gram-positive, then we should be able to gather enough data to determine our position to move forward and eventually license out the technology.”