Navigation Links
Boston University Biomedical Engineers Find Chink in Bacteria's Armor
Date:9/6/2007

Find Could Lead to More Effective Antibiotics Against 'Superbugs'

BOSTON, Sept. 6 /PRNewswire-USNewswire/ -- Biomedical researchers at Boston University's College of Engineering may have discovered the path toward developing better drugs capable of defeating so-called "superbugs," bacteria that have developed resistance to common antibiotics. The researchers have discovered a previously unknown chain of events occurring in bacteria that opens to door to new avenues of research.

Currently, three classes of bactericidal antibiotics are used to target different bacterial functions: inhibiting DNA replication; blocking protein-building; or halting construction of cell walls. Research from the laboratory of Professor James Collins found the three classes more alike than anyone realized, and the commonalities may be the bugs' downfall.

Collins and colleagues' article, "A Common Mechanism of Cellular Death Induced by Bactericidal Antibiotics," appears in the September 7 issue of Cell.

The researchers discovered a common process, or pathway, that was triggered by all three types of antibiotics. "There's an underlying pathway beyond the drug interacting with the target," said graduate student and lead author Michael Kohanski, "and the endpoint of this pathway is excessive free radical production."

Free radicals - such as hydroxyl or superoxide radicals - are molecules that carry a free, or unpaired, electron like a weapon. "They'll damage DNA, proteins, lipids in the membrane, pretty much anything. They're equal opportunity damagers," said Kohanski.

This hidden pathway and resultant free radical overload appears to help current antibiotics do their job, but is not always enough to kill all bacteria by itself. Collins' group theorizes that if this effect can be amplified, or if the cell's genetic defense against it can be weakened, no bacteria could withstand its effect and the emergence of antibiotic-resistant bacteria could be limited.

"Importantly, we showed that if you can inhibit or block the bacterial defense mechanisms to hydroxyl radical damage, you can potentiate or enhance the lethality of bactericidal antibiotics. This highlights the value of taking a network biology approach to antibiotics and provides a framework for creating new classes of drugs," said Collins.

"What we think is happening is the cell is getting a signal that says, 'There's something wrong with our energy production system and we need to make more energy.' But, there's really nothing wrong. The cell becomes confused, turns on too many processes at once and it's overwhelmed," said Kohanski.

Previous work by Kohanski and co-lead author Dan Dwyer, a postdoctoral researcher in Collins' lab, revealed the first hints that this underlying pathway exists. In studying bacterial response to a quinolone, an antibiotic that inhibits DNA replication, they noted a surprising change in genes responsible for energy production and iron uptake.

In the current study, the researchers used DNA microarray studies to see if all three classes of bactericidal antibiotics triggered this process. Across the board, they noted increased gene activity along the intracellular assembly lines that make energy for the bacterial cell, just as in the earlier study. They began to deduce the details of the new pathway.

Cells produce free superoxide radicals naturally in oxygen-rich environments, but when they unnecessarily ramp up energy production to a frantic pace - such as when triggered by antibiotics - more radicals get churned out than the cell's safety measures can mop up. The superoxide radicals then pull iron from other components of the cell, and this iron rapidly stimulates production of toxic levels of hydroxyl radicals.

"It's really amazing that despite the diversity of targets, you have everything funneling into this common pathway, where there's a global meltdown occurring," said Dwyer. "There's almost no way for the cell to recover from this. It shows you how potent these molecules are to damaging and killing the cell."

In addition to potentially making bacteria more vulnerable to current drugs, this finding may revitalize development of antibiotic drugs sidelined because of narrow differences between therapeutic and toxic doses. Such drugs might re-enter the pipeline, if this free-radical producing pathway is exploited to lower the therapeutic dose, making formerly dangerous drugs safer.

AUTHOR CONTACT INFORMATION

Professor James Collins

Boston University College of Engineering

(617) 353-0390

jcollins@bu.edu

PHOTOS

High-resolution photos of the research team area available by e-mailing mseele@bu.edu.


'/>"/>
SOURCE Boston University College of Engineering
Copyright©2007 PR Newswire.
All rights reserved

Related medicine technology :

1. Boston Scientific Announces Schedule for EuroPcr 2007
2. Boston Life Sciences, Inc. Announces Presentation of Cethrin Phase I/IIa 6-Month Results at 75th Annual Meeting of the American Association of Neurological Surgeons
3. Bio-Matrix Scientifics Dr. ONeill Sees University of Pittsburghs Published Study on Culture Blood-Forming Stem Cells from Human Fat Tissue as Supporting Near Term Benefits of Banking Adipose (Fat) Derived Stem Cells
4. Prolexys Pharmaceuticals and Columbia University Researchers Publish Study on Anti-Tumor Properties of a Selective Small Molecule Anti-Tumor Agent With Novel Mechanism of Action
5. Statement by Philip Home Chairman of the RECORD Study Steering Committee and Professor of Diabetes Medicine at Newcastle University in England
6. World First Medical Treatment Announced by Researchers at Queen Mary University London and University of Leicester
7. Alnylam and Stanford University Scientists Discover New Role for microRNAs (miRNAs) in T Cell Biology and Immunity
8. Vaxiion Researchers Discover Novel Vaccine Delivery System in Collaboration with San Diego State University
9. Vical Interim Clinical Results Demonstrate Safety and Tolerability of Inovio Biomedicals Electroporation DNA Delivery Technology
10. Inovio Biomedical Highlights Enhanced DNA Vaccine Potency with Electroporation DNA Delivery Technology and New Devices at Gene Therapy Meeting
11. Inovio Biomedicals DNA Delivery Technology Shows Safety and Enhances Gene Expression & Tumor Responses in Interim Melanoma Clinical Study Results
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/12/2017)... AVACEN Medical , Inc. (AVACEN) announced that ... New Product Innovation Award for Its fibromyalgia pain management ... medical device market research by Frost & Sullivan,s industry experts. ... pain relief product, the AVACEN 100, offers a safe and ... pain. ...
(Date:10/11/2017)... 2017  True Health, a leader in integrated ... during National Breast Cancer Awareness month to educate ... Research recently published ... more than 10 million American women are at ... or BRCA2 and have not had testing. These mutations ...
(Date:10/5/2017)... , Oct. 5, 2017  In response ... of Oral and Maxillofacial Surgeons (AAOMS) released prescribing ... – to be used as a first-line therapy ... Recognizing the ... AAOMS White Paper "Opioid Prescribing: Acute and Postoperative ...
Breaking Medicine Technology:
(Date:10/13/2017)... ... October 13, 2017 , ... While it’s often important to take ... an inventor from Austin, Texas, has identified a solution. , She developed a prototype ... restricted lighting. As such, it eliminates the need to turn on a light when ...
(Date:10/13/2017)... ... October 13, 2017 , ... Southern ... and Jennifer Huggins, PharmD ’17, along with clinical associate professor Janice Frueh, ... cardiovascular diseases during the 15th Annual Women’s Health Conference. The SIU School ...
(Date:10/13/2017)... RIDGE, N.J. (PRWEB) , ... October 13, 2017 , ... ... annual Holly Day Market. Featuring a collection of specialty vendors and unique items from ... of personalized and quality-focused health and wellness services offered by the VNA. The ...
(Date:10/13/2017)... ... October 13, 2017 , ... Talented ... the lowdown on sciatica in a new episode of "Success Files," which is ... events and innovation and investigates each subject in-depth with passion and integrity. , ...
(Date:10/12/2017)... ... October 12, 2017 , ... First Healthcare Compliance (FHC), an ... showcase a range of technology and learning solutions at the 68th Annual American ... to be held October 14–18, 2017 at the Mandalay Bay Resort in Las ...
Breaking Medicine News(10 mins):