Nav: Home

Boston College team reports technology to enable precision antibiotics

June 27, 2018

Chestnut Hill, Mass. (6/27/2018) - Scientists are searching for ways to develop antibiotics that can accurately target infectious bacteria. Increased specificity could help to combat antibiotic resistance and also spare "good" bacteria from being attacked by broad-spectrum antibiotics.

Efforts to develop targeted antibiotics have been constrained by the difficulty of quick diagnosis and the development of targeted killing mechanisms.

A collaborative effort of two Boston College professors - a chemist and a biologist - has led to a new platform to enable quick discovery of molecules that potentially recognize any strain of bacteria of interest, the team reported recently in the Journal of the American Chemical Society.

The new approach is based on phage display, a proven strategy used to create and screen peptide libraries containing billions of different composite members displayed on bacteriophage. While a powerful tool, phage display has been limited to use with the peptides of natural amino acids, the researchers noted.

Associate Professor of Chemistry Jianmin Gao and Associate Professor of Biology Tim van Opijnen set out to expand the "chemical space" of phage display by incorporating designer chemical warheads that dramatically enhance a peptide's potency to bind biological targets.

Screening of this chemical enhanced library against live bacteria produced powerful, highly-selective probes to target two deadly antibiotic-resistant bacterial pathogens: methicillin-resistant Staphylococcus aureus and colistin-resistant Acinetobacter baumannii, the team reported in an article titled "Phage Display of Dynamic Covalent Binding Motifs Enables Facile Development of Targeted Antibiotics."

Gao said the designer chemical warheads introduce into the phage library a "reversible covalent binding mechanism," which is absent in peptides of natural amino acids. The chemically enhanced peptide library allows potent and selective targeting of a bacterium of interest, overcoming biological conditions that interfere with bonding to pathogens and avoiding healthy human cells.

"The 'warhead' allows us to come up with molecules with enhanced potency and selectivity toward a bacterial strain of interest," said Gao, whose research is supported by the National Institutes of Health. "Now we have a much better library to use for screening and identifying the strains of these specific bacterial molecules."

In further experiments, Gao and van Opijnen successfully attached a generic toxin to these bacterium-targeting molecules, a significant step forward imparting specificity in the treatment of the two strains of bacterium.

"This new, modified phage library shows it can be a powerful, multipurpose tool," said Gao. "First, it can be used to generate imaging agents to confirm a suspected bacterial infection. These probes will go around and look for infected bacteria. Find them and attach to them. Second, we can attach an antibiotic and the probe will serve to deliver the toxin to the only that strain of bacteria. This gets us closer to narrow-spectrum antibiotics."

Gao and van Opijnen said the novel approach should be applicable to a wide range of bacterial pathogens, enabling the development of targeted antibiotics.

"This is a first step toward that long-term goal," said Gao. "We would like to expand this promising approach to develop targeted antibiotics that treat these specific strains of deadly and damaging pathogens."

Gao said advances in targeted antibiotics will improve patient care, and reduce the "strain" placed on necessary bacteria and their evolution of antibiotic resistance.

"With treatment from broad-spectrum antibiotics, all bacteria in the body feel the strain and they evolve to resist antibiotics," said Gao. "So our currently available antibiotics are forcing the fast acquisition of resistance, which is undesirable. Ideally we would like to come up with something that targets disease-causing bacteria selectively. Treat that strain and only that strain and that way we don't have to wipe out the good bacteria."

In addition to Gao and van Opijnen, the team included Boston College researchers Kelly A. McCarthy, Michael A. Kelly, Kaicheng Li, Samantha Cambray, and Azade S. Hosseini. Patrick Autissier, manager of BC's Cell Sorting Facility, provided flow cytometry analysis.
-end-


Boston College

Related Bacteria Articles:

Conducting shell for bacteria
Under anaerobic conditions, certain bacteria can produce electricity. This behavior can be exploited in microbial fuel cells, with a special focus on wastewater treatment schemes.
Controlling bacteria's necessary evil
Until now, scientists have only had a murky understanding of how these relationships arise.
Bacteria take a deadly risk to survive
Bacteria need mutations -- changes in their DNA code -- to survive under difficult circumstances.
How bacteria hunt other bacteria
A bacterial species that hunts other bacteria has attracted interest as a potential antibiotic, but exactly how this predator tracks down its prey has not been clear.
Chlamydia: How bacteria take over control
To survive in human cells, chlamydiae have a lot of tricks in store.
Stress may protect -- at least in bacteria
Antibiotics harm bacteria and stress them. Trimethoprim, an antibiotic, inhibits the growth of the bacterium Escherichia coli and induces a stress response.
'Pulling' bacteria out of blood
Magnets instead of antibiotics could provide a possible new treatment method for blood infection.
New findings detail how beneficial bacteria in the nose suppress pathogenic bacteria
Staphylococcus aureus is a common colonizer of the human body.
Understanding your bacteria
New insight into bacterial cell division could lead to advancements in the fight against harmful bacteria.
Bacteria are individualists
Cells respond differently to lack of nutrients.

Related Bacteria Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Bias And Perception
How does bias distort our thinking, our listening, our beliefs... and even our search results? How can we fight it? This hour, TED speakers explore ideas about the unconscious biases that shape us. Guests include writer and broadcaster Yassmin Abdel-Magied, climatologist J. Marshall Shepherd, journalist Andreas Ekström, and experimental psychologist Tony Salvador.
Now Playing: Science for the People

#513 Dinosaur Tails
This week: dinosaurs! We're discussing dinosaur tails, bipedalism, paleontology public outreach, dinosaur MOOCs, and other neat dinosaur related things with Dr. Scott Persons from the University of Alberta, who is also the author of the book "Dinosaurs of the Alberta Badlands".