MAR 16, 2015 11:06 AM PDT

'Warhead' Molecule to Hunt Down Deadly Bacteria

WRITTEN BY: Judy O'Rourke
Targeting deadly, drug-resistant bacteria poses a serious challenge to researchers looking for antibiotics that can kill pathogens without causing collateral damage in human cells. A team of Boston College chemists details a new approach using a "warhead" molecule to attack bacteria -- and spare healthy human cells -- by targeting a pair of lipids found on the surface of deadly germs, according to a report today in the journal Nature Communications.

The new strategy required the researchers to develop a novel type of "warhead molecule" capable of selectively targeting bacteria, overcoming biological conditions that interfere with bonding to pathogens and avoiding healthy human cells, says Jianmin Gao, PhD, associate professor of chemistry and the lead author of the report.
This is a colorized scanning electron micrograph of a white blood cell eating an antibiotic resistant strain of Staphylococcus aureus bacteria (MRSA).
The BC team found answers to those challenges in the covalent chemistry of lipids, Gao says.

"In contrast to other efforts focused on the charge-to-charge attraction between molecules, we are using a completely different mechanism to target bacterial cells," Gao says. "Our method exploits the covalent chemistry of lipids -- where the lipids react with synthetic molecules to form new chemical structures based on the formation of new covalent bonds."

Pathogenic bacteria that are resistant to conventional antibiotics pose increasingly serious threats to public health. Researchers in medicinal chemistry, particularly those who seek to develop new antibiotics, are constantly looking for new ways to identify and differentiate bacterial pathogens from host cells within the human body.

Gao says bacterial cells are known to display a different set of lipids in their membranes. Prior research has focused on the use of positively charged peptides to target negatively charged lipids on the surface of bacterial cells. The approach has seen limited success as the charge-charge attraction between the attacking molecules and bacteria is prone to weakening by the presence of salt and other molecules, said Gao.

The researchers developed a novel, unnatural amino acid that serves as a suitable molecular warhead to target bacterial pathogens. Gao and his group sent the warhead molecule after bacterial lipids known as amine-presenting lipids -- specifically phosphatidylethanolamine (PE) and lysyl phosphatidylglycerol (Lys-PG) -- which can be selectively derivatized to form iminoboronates, a covalent bond forming process that allows the selective recognition and labeling of bacterial cells.

In addition, because amine-presenting lipids are scarce on the surface of mammalian cells, they are able to seek out and label bacterial cells with a high degree of selectivity, Gao says. Furthermore, iminoboronate formation can be reversed under physiologic conditions, giving the new method a high degree of control and allowing the warhead molecules to self-correct if unintended targets are reached.

Gao says a large number of bacterial species present PE and Lys-PG on their surfaces, making the covalent labeling strategy applicable to many applications in the diagnosis of bacterial infections and the delivery of antibiotic therapies.

"For the short term, we hope this work will inspire other people to consider using covalent chemistry for interrogating biological systems," Gao says. "Going into the future, we are excited to explore the potential of our chemistry for imaging bacterial infections. We are also working hard to apply our current findings to facilitate the targeted delivery of potent antibiotics to bacterial cells only."

[Source: Boston College]
About the Author
  • Judy O'Rourke worked as a newspaper reporter before becoming chief editor of Clinical Lab Products magazine. As a freelance writer today, she is interested in finding the story behind the latest developments in medicine and science, and in learning what lies ahead.
You May Also Like
AUG 28, 2020
Microbiology
As Buildings Reopen After Lockdowns, They Find Legionella
AUG 28, 2020
As Buildings Reopen After Lockdowns, They Find Legionella
Several schools and even buildings at the Centers for Disease Control and Prevention (CDC) have identified Legionella ba ...
AUG 29, 2020
Cell & Molecular Biology
Together, Two Gut Microbes Have a Nasty Effect
AUG 29, 2020
Together, Two Gut Microbes Have a Nasty Effect
The microbes in the human gut play important roles in our physiology, and they can also contribute to disease. But they ...
SEP 22, 2020
Cardiology
Mosquito-Borne Illnesses are Linked to Stroke
SEP 22, 2020
Mosquito-Borne Illnesses are Linked to Stroke
Mosquitoes are major disease vectors; they are considered the world's deadliest animal because they kill so many people.
OCT 11, 2020
Microbiology
Getting Closer to a Vaccine for Flaviviruses
OCT 11, 2020
Getting Closer to a Vaccine for Flaviviruses
Flaviviruses like dengue, West Nile, Zika, Japanese Encephalitis, and yellow fever infect over 400 million people a year ...
OCT 15, 2020
Microbiology
WHO Data Suggests Remdesivir Has No Effect on COVID-19 Infections
OCT 15, 2020
WHO Data Suggests Remdesivir Has No Effect on COVID-19 Infections
While the study has not yet been peer-reviewed, an International consortium including researchers has come to the conclu ...
NOV 05, 2020
Clinical & Molecular DX
Digging DEEP into Metabolomic Space
NOV 05, 2020
Digging DEEP into Metabolomic Space
Metabolomics is an umbrella term encompassing lipidomics and the study of smaller polar metabolites.  As such, more ...
Loading Comments...