The Ocean as a Key Resource in the Antibiotics Arms Race

Shreya Kishore ’21 in the Whalen Lab at Haverford College.

Shreya Kishore is currently a senior Chemistry major with a biochemistry concentration and health studies minor at Haverford College. As a peer tutor and member of the Chemistry Student Group, Kishore is passionate about increasing the transparency of Haverford’s chemistry department. She plans on working toward her Chemistry PhD at Stanford University this fall.

One key solution to fighting antibiotic resistance is to discover new antibiotics. Shreya Kishore ’21 shares how she screens marine bacterial cultures in pursuit of discovering a novel antibiotic.

Almost 100 years ago, Sir Alexander Fleming accidentally discovered a fungus, Penicillium notatum, growing in a petri dish of Staphylococcus bacteria he had accidentally left uncovered by an open window. Penicillins, the antibiotic chemicals produced by P. notatum, are now the most highly used class of antibiotics in the world. Since Fleming’s discovery, antibiotics have saved millions of lives and transformed the field of medicine.

Antibiotics work by either killing bacteria or inhibiting bacterial cell growth and division. However, antibiotics also introduce an environmental pressure that allows resistant bacterial cells to survive, reproduce, and pass on this resistance. They can also transfer resistance to other bacterial cells, a process known as horizontal gene transfer. Increased administration of antibiotics exposes more bacteria to this environmental pressure, thus accelerating resistance-building to a given antibiotic.

CDC infographic on how antibiotic resistance occurs and spreads.

After penicillin became widely available in the 1940s, the world entered a “Golden Age” of antibiotic discovery until the last class of antibiotics was discovered in 1987. This marked the start of a “Discovery Void” in which no new classes of antibiotics have been discovered and scientists have observed a marked drop in antibiotic discovery. Due to the lack of economic incentive, most pharmaceutical companies have stopped investing in antibiotic development in recent years. The effects of this Discovery Void worsen by the year as infectious bacteria become more exposed to — and thus increasingly resistant to — our current drugs. 

The decline of new antibiotic discoveries and general overuse of antibiotics — through livestock feed, agriculture, and overprescription by doctors and healthcare providers — are simultaneously contributing to the problem. The CDC has repeatedly emphasized the severity of this trend, stating that “antibiotic resistance is one of the biggest public health challenges of our time.” 

Predicted distribution of deaths attributable to antimicrobial resistance (AMR) every year by 2050. Via the United Nations Foundation (2017).

Novel antibiotics can be developed from bacterial metabolites (natural metabolic byproducts) found in nature. In an environment with limited nutrients, bacteria produce antimicrobial compounds to kill or halt the growth of their microbial competitors. For decades, scientists have been looking to microbially rich sources such as soil, but more recently, researchers have started looking into marine natural products to harness the ocean’s distinct and vast biodiversity.

Shreya Kishore ’21 is currently examining marine natural products in order to discover a novel antibiotic. In the Whalen Lab, Kishore examines and grows marine bacterial culture samples, extracting each of its produced compounds. She searches for antimicrobial compounds within each culture that can be developed into antibiotics or act as efflux pump inhibitors.

Kishore explains that efflux pumps are located within bacterial membranes and pump antibiotics out of the cell. Since efflux pumps are non-specific — meaning that they can work on many different types of antibiotics — they are another way bacteria become multi-drug resistant. An efflux pump inhibitor (EPI) would block the function of efflux pumps, which can renew the effectiveness of an antibiotic for the bacteria. According to Kishore, finding either a novel antibiotic or an EPI “would have a broad clinical application.”

In the lab, Kishore screened about 500 marine cultures and found about 20 to be active, meaning that they indicated effectiveness against pathogenic bacteria. Kishore’s next step is to locate the exact compound within each culture that is responsible for the observed effect, and to find the mechanism by which these active compounds inhibit bacterial growth.

In addition to working toward discovering a novel antibiotic, Kishore and other researchers in the Whalen Lab are also screening a novel antibiotic identified in 2018 by Anna Schrecengost ’18, who used similar methods to analyze marine natural products. Kishore is currently testing the antibiotic against different human pathogenic bacteria.

Because bacteria are continually developing resistance to antibiotics, the world is currently in an arms race against pathogenic bacteria. Dr. Keiji Fukada, the Assistant Director-General for Health Security at the WHO, says that if action is not taken, “common infections and minor injuries which have been treatable for decades can once again kill.”

Kishore is well aware of the urgent need for novel antibiotics and is excited to be a part of the fight. “If we run out of effective antibiotics,” she notes, “even simple surgeries like appendectomies can become life threatening.”

This article was edited by Nora Reidy, Lucy Zhao, and Griffin Kaulbach.