Antimicrobial Resistance: Facing Tomorrow's Problems Today

Antimicrobial Resistance: Facing Tomorrow's Problems, Today

Worldwide, the threat of antimicrobial resistance (AMR) is already responsible for more than 1 million deaths every year, a total that is projected to rise to 10 million annual deaths by 2050. Amid these growing concerns, microbiologists are looking toward something new and something old—artificial intelligence (AI) and phage therapy—to help mitigate the effects of AMR, while ensuring therapeutics are delivered equitably to patients. Here, we explore some of the unique perspectives being taken by ASM members to identify and address current and future challenges.

Artificial Intelligence Tools for Developing Antimicrobials and Antifungals

Given the immediate threat posed by AMR, improving the efficiency of antibiotic discovery is imperative. Unfortunately, current efforts are not keeping pace. “Right now, we have 3 classes of drugs that are used to treat fungal infections that are life threatening,” said Damian Krysan, M.D., Ph.D., from the University of Iowa Carver College of Medicine. “Where is the next drug going to come from?”

That is where AI comes in. “Artificial intelligence is revolutionizing all fields, including antibiotic discovery,” said Silvia Cardona, Ph.D., from the University of Manitoba. Cardona has already started applying machine learning AI in her own work, which centers on developing chemogenetic profiles of essential gene knockdowns in order to better predict antibiotic activity. “How,” she asked, “can we make it smarter to find new molecules?”

Only a handful of novel antifungal agents are currently under investigation.
Only a handful of novel antifungal agents are currently under investigation.
Source: Fernandes et al. (2021) doi: 10.1128/AAC.01719-20

Such development is critical. In a 5-year span (2014-2019) only 14 new antibiotics were approved for use. However, research estimates suggest that 1030-1060 drug-like molecules potentially exist—orders of magnitude beyond what humans could possibly hope to investigate using traditional methods, but well within reach of AI systems.

As Krysan explained, AI technology “is not going to help make new data, but it can take existing data and find patterns that would take a person just sitting there looking at Excel spreadsheets forever.” Cardona also emphasized the benefits of AI compared to current techniques. “A high-throughput screen is expensive and takes lots of time and resources,” she explained. “If we can train computers to predict which molecules have a better chance to be converted into antibiotics, then we save time.”

Krysan and Cardona co-organized a session at ASM Microbe 2023 titled "Where Will We Find the Next Generation of Antimicrobials/Antifungals?” The session explored how researchers are using AI in different ways to identify new drug candidates, including through screening chemical compounds, analysis of microscopic images and exploration of metabolic pathways.

As interest in AI has exploded worldwide, Cardona feels that exploring and learning about the benefits and limitations of the technology are critical. “I think that what matters the most is not to be afraid of AI: learn about it, learn how to use it properly,” she emphasized. “If we don't educate ourselves about what it is and how to use it, then we will end up having a society that fears it. That's not how it should be.”

Use of Phage Therapy to Address Antimicrobial Resistance

Artist representation of phage viruses.Researchers are exploring the viability of phage therapy to combat AMR.
Source: iStock
In addition to the decidedly 21st century approach that is AI, researchers are also exploring a much more retro technique to counter AMR: phage therapy.

As Heidi B. Kaplan, Ph.D., from McGovern Medical School at the University of Texas Health Sciences Center at Houston explained, phage therapy “is a technology that we're re-visiting.” Initially developed in the early 1900s, the technique fell out of favor during the second half of the 20th century. However, recent research has suggested phage therapy as a potentially effective alternative to the use of antibiotics to combat AMR.

The key to phage therapy is that it can be used to target multidrug-resistant infections. In contrast to broad-spectrum antibiotics, phage are “very specific for the bacteria that they kill,” said Kaplan. What that means is that phage can be applied selectively and not interfere with the delicate balance that exists within established microbiomes.

Furthermore, whereas bacteria can develop permanent resistance to a static antibiotic, phage are able to keep up with an evolutionary arms race. “If bacteria develop resistance to the phage, you can evolve a related phage in the laboratory that can newly infect the resistant bacteria, or you can isolate a new phage from the environment,” Kaplan said.

However, widespread implementation of phage therapy will require large-scale clinical trials to study the safety and efficacy of appropriate candidates. Clinically, “I think we're years away from widespread use,” predicted Kaplan. “In addition to the FDA approval, physicians will need to feel comfortable with this new strategy.”

Kaplan convened several leaders in the field of phage therapy for a session at ASM Microbe 2023 that explored the current state of research, novel clinical approaches and recent commercial developments. The session was titled "New Perspectives on Phage Therapy to Treat Multidrug Resistant Infections.”

Equity, Social Justice and Antimicrobial Resistance

While addressing scientific and medical challenges related to combatting AMR is of paramount importance, if the solutions and interventions don’t end up reaching patients and susceptible groups, are they truly impactful?

That is an issue that Jacinda Abdul-Mutakabbir, Pharm.D., MPH, from the University of California San Diego is trying to address. “How is it,” Abdul-Mutakabbir asked, “that we ensure equitable stewardship measures and policies [related to AMR]?"

Such discussion is not just theoretical. The COVID-19 pandemic has laid bare significant racial and ethnic disparities in virus-associated mortality, along with vaccination rates. Hoping to prevent similar disparities from occurring in the looming AMR crisis, Abdul-Mutakabbir is working to establish “stewardship that really tries to ensure that everyone receives the most appropriate therapies, at the most appropriate time, for the most appropriate durations, and that we're making sure that all of these things are done equitably.”

Profile pictures of AMR session panelists.
Speakers at the "Antimicrobial Stewardship Programs: Beyond the Looking Glass" session at ASM Microbe explored how approaches addressing AMR can be delivered equitably. Pictured left to right: Sara Alosaimy (Wayne State University), Kierra M. Dotson (Chase Brexton Health Care), Anna Zhou (Loma Linda University), Jacinda Abdul-Mutakabbir (UCSD).
Source: American Society for Microbiology

Addressing these challenges relies on improving trust, access, diversity and inclusion. “The institution of science is led by senior investigators who are typically male and/or white. When you do have diversification, it still continues to lack the representation of minoritized professionals, especially those that are at the junior and mid-career levels,” said Abdul-Mutakabbir. “How is it that antimicrobial stewardship may be impacted when we don't have people at the table?” she asked.

One particular example of this problem focuses on sources of care. As Abdul-Mutakabbir explained, “People that go to federally qualified health centers (FQHCs) are more likely to be minoritized, and we don't really showcase what stewardship and antimicrobial resistance look like in these health centers.”

To help address these issues, Abdul-Mutakabbir organized a session at ASM Microbe 2023 that featured diverse panelists who encounter and explore these challenges from unique perspectives. The session was titled "Antimicrobial Stewardship Programs: Beyond the Looking Glass."

“I really wanted to see the different groups that you don't typically see having those opportunities to speak about their professions and their contributions,” she explained. “I really wanted to make sure that we saw traditionally marginalized groups represented amongst the speakers."

Having diverse viewpoints included in conversations about antimicrobial stewardship will, according to Abdul-Mutakabbir, help members of the scientific and medical communities broaden their perspectives and improve the impact of their own work. “It allows for us to be able to call out some of our own biases, to get outside of what we've been taught—what has traditionally been done—and really be innovative,” she said. “By calling these things out, the way that we provide care can look a lot different.”

Antimicrobial Resistance Experts Connected at ASM Microbe 2023

From tapping AI to predict antibiotic activity, to leveraging phage therapy to vanquish multi-drug resistant infections, scientists who gathered at ASM Microbe 2023 addressed AMR from every angle. The Antimicrobial Agents and Resistance track offered a hub to discuss multi-pronged strategies to tackle the grave challenge of AMR and ensure equitable health care practices are implemented.

Author: Geoff Hunt

Geoff Hunt
Geoff Hunt, Ph.D., is the Public Outreach Program Officer at the American Society for Microbiology. Geoff received his B.A. from Cornell University in 2003 with a degree in biochemistry, and got his Ph.D. in molecular biology from Princeton University.