How bacteria develop resistance to antibiotics

Researchers are examining how engineering biology can illuminate and help solve pressing challenges, including antimicrobial resistance. At Boston University’s Biological Design Center, Biomedical Engineering Professor Mary Dunlop studies how microbes sense and respond to their environments, according to Boston University. Her team investigates how bacteria adapt and use those insights to understand biological systems and engineer new interactions with cells.

Engineering Biology and Microbial Adaptation

A central insight from this research is that genetically identical bacteria can behave very differently. When exposed to the same antibiotic, some cells survive while others do not. To study this behavior, the Dunlop Lab introduces light-responsive components from other organisms into bacteria in a method known as optogenetics. This technique allows researchers to control cellular activity in real time and mimic processes that happen during the initial stages of drug resistance evolution.

Synthetic Biology and Artificial Intelligence Approaches

To address the growing global threat of antimicrobial resistance, James J. Collins, the Termeer Professor of Medical Engineering and Science at Massachusetts Institute of Technology, is leading a multidisciplinary research project applying synthetic biology and generative artificial intelligence. The initial three-year, $3 million research project is sponsored by Jameel Research and centers in MIT’s Department of Biological Engineering and Institute of Medical Engineering and Science.

The initiative focuses on developing and validating programmable antibacterials against key pathogens by using AI to design small proteins that disable specific bacterial functions. These designer molecules would be produced and delivered by engineered microbes. According to Collins, tackling antimicrobial resistance requires both bold scientific ideas and a pathway to real-world impact. Mohammed Abdul Latif Jameel ’78, chair of Abdul Latif Jameel, noted that antimicrobial resistance is one of the most urgent challenges facing global health.

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Gene-Modulating Platforms and Resistance Mechanisms

Other groups are also utilizing advanced genetic approaches to target bacterial resistance. Venus Remedies, through the Venus Medicine Research Centre in Panchkula, uses CRISPR-based and gene-modulating approaches to selectively disable high-impact bacterial resistance mechanisms, according to Biospectrumindia. Saransh Chaudhary, President of Global Critical Care at Venus Remedies and CEO of the research center, stated that cell and gene therapies offer a programmable way to overcome bacterial resistance.

Content cover image
Photo: Nature

CRISPR-Cas systems can be designed to selectively disable specific resistance genes in bacterial genomes to restore susceptibility to existing drugs. Despite this potential, significant translational challenges remain. Getting genetic payloads to reliably reach bacterial cells inside a living host remains an unsolved problem, as viral vectors used in mammalian gene therapy do not translate to bacteria. Phage-based delivery alternatives also face limitations such as narrow host ranges, immune clearance, manufacturing scaling difficulties, and the challenge of reaching bacteria embedded in biofilms or deep tissue infections.

Bacterial Biofilms and Historical Context

Antimicrobial resistance is exacerbated by the formation of biofilms, which are complex structures formed when bacterial colonies stick to a surface and encase themselves in extracellular polymeric compounds consisting of proteins, eDNA, and polysaccharides. According to Frontiersin, these biofilms exhibit strong antibiotic resistance that increases morbidity and death.

How bacteria develop resistance to antibiotics
Photo: MIT

Research into biofilms and bacterial resistance has a long history, dating back to Antonie van Leeuwenhoek observing animalcules on his teeth in the 17th century. Later milestones include Alexander Fleming discovering penicillin in 1928, which entered clinical usage in the 1940s. Within four years of penicillin usage, the first strains of resistant bacteria appeared, setting the stage for the modern challenge of antimicrobial resistance driven by continuous exposure and the indiscriminate use of antibiotics in clinical and farming environments.

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