Paper Clip: Resisting the resistance to antibiotics

Resistance to antibiotics is rising worldwide, including in India, and emerging as a powerful threat to public health, as the ability to fight infections such as tuberculosis is diminished.

By: Express News Service | Published: September 24, 2015 12:20 am

MEDICINE: BIOLOGICAL ENGINEERING

Nano Letters, published June 2015

Authors: James J Collins, Russell J Krom and Others

Resistance to antibiotics is rising worldwide, including in India, and emerging as a powerful threat to public health, as the ability to fight infections such as tuberculosis is diminished. Efforts to develop new antibiotics have not been able to keep pace with the growth in microbial resistance.

The researchers, from MIT, the Broad Institute of MIT and Harvard, and Harvard University, report that they have developed a new way to destroy harmful bacteria — by engineering particles, known as “phagemids”, that produce toxins that are deadly to targeted bacteria.

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Bacteriophages, that is, viruses that infect and kill bacteria, have for long been in a limited fashion to treat bacterial infections. However, this approach can result in the release of harmful endotoxins, leading to untoward side effects, the researchers have written.

“Bacteriophages kill bacteria by lysing the cell, or causing it to burst,” lead researcher James J Collins was quoted as saying in MIT News, a journal of research on campus. “But this is problematic, as it can lead to the release of nasty toxins from the cell.” These toxins can lead to sepsis and even death in some cases, Collins said.

Collins and his colleagues had earlier engineered bacteriophages to express proteins that did not actually burst the cells, but instead increased the effectiveness of antibiotics when delivered at the same time.

Building on this work, the researchers attempted to develop a related technology that would target and kill specific bacteria, without bursting the cells and releasing their contents. They used synthetic biology techniques to develop a platform of phagemids, which infect bacteria with small DNA molecules known as plasmids, which are able to replicate independently inside a host cell.

Once inside the cell, the plasmids are engineered to express different proteins or peptides — molecules made up of short chains of amino acids — that are toxic to the bacteria, Collins said.

The expressed toxins are designed to disrupt different cellular processes, such as bacterial replication, causing the cell to die without bursting open. The phagemids also only infect a specific species of bacteria, resulting in a highly targeted system, Collins said.

This work shows that targeted, engineered phagemid therapy can serve as a viable, non-antibiotic means to treat bacterial infections, while avoiding the health issues inherent to lytic and replicative bacteriophage use, the authors have written in the study.

— ADAPTED FROM MIT NEWS & STUDY ABSTRACT

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