Navigation Links
Boston University biomedical engineers find chink in bacteria's armor
Date:9/6/2007

Biomedical researchers at Boston Universitys 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. Theres 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. Theyll damage DNA, proteins, lipids in the membrane, pretty much anything. Theyre 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 cells 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, Theres something wrong with our energy production system and we need to make more energy. But, theres really nothing wrong. The cell becomes confused, turns on too many processes at once and its 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 cells 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.

Its really amazing that despite the diversity of targets, you have everything funneling into this common pathway, where theres a global meltdown occurring, said Dwyer. Theres 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.


'/>"/>

Contact: Mike Seele
mseele@bu.edu
617-353-9766
Boston University
Source:Eurekalert

Related biology news :

1. Boston University biomedical engineers win major grant for pursuit of the $1,000 Genome
2. University of Manchester makes made-to-measure skin and bones a reality using inkjet printers
3. New protein discovered by Hebrew University researchers
4. Next Generation Body Scanner Launched By The University Of Manchester
5. Roundup®highly lethal to amphibians, finds University of Pittsburgh researcher
6. Green catalyst destroys pesticides and munitions toxins, finds Carnegie Mellon University
7. University of Nevada, Reno research team discovers hormone that causes malaria mosquito to urinate
8. Carnegie Mellon University research reveals how cells process large genes
9. University of Delaware researchers develop cancer nanobomb
10. University of Arizona plant scientists to unravel maize genome
11. Team led by Carnegie Mellon University scientist finds first evidence of a living memory trace
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/6/2016)... WARSAW, Ind. , Dec. 6, 2016  Zimmer Biomet ... that it has priced an offering of €500.0 million principal ... €500.0 million principal amount of its 2.425% senior unsecured notes ... is expected to occur on December 13, 2016, subject to the ... on an annual basis. ...
(Date:12/2/2016)... 2016 The report "Biometric Vehicle ... Technology (Iris Recognition System), Vehicle Type (Passenger Car, ... to 2021", published by MarketsandMarkets, the market is ... and is projected to grow to USD 854.8 ...      (Logo: http://photos.prnewswire.com/prnh/20160303/792302) ...
(Date:11/29/2016)... BOSTON , Nov. 29, 2016 BioDirection, ... rapid point-of-care products for the objective detection of concussion ... the company has successfully completed a meeting with the ... company,s Tbit™ blood test Pre-Submission Package. During the meeting ... Tbit™ system as a precursor to commencement of a ...
Breaking Biology News(10 mins):
(Date:12/7/2016)... report "Acrylic Processing Aid Market by Polymer Type (PVC), Fabrication Process (Extrusion, Injection Molding), End-Use ... published by MarketsandMarkets, the global market size was USD 645.4 Million in 2016, ... CAGR of 6.2% between 2016 and 2026. Continue ... ... , , ...
(Date:12/7/2016)... 2016  Genprex, Inc. a biopharmaceutical company focused ... today announced that it has retained ICR Healthcare, ... communications and advisory firm, to develop and implement ... combine investor relations, public relations and digital communications ... of Genprex and its lead candidate Oncoprex, which ...
(Date:12/7/2016)... and ANN ARBOR, Mich. , ... biopharmaceutical company developing breakthrough immune modulatory medicines, announced today ... the Company,s lead therapeutic candidate, LYC-30937- E nteric ... a debilitating skin disease that is estimated to affect ... United States , with approximately 1.5 - 3 ...
(Date:12/7/2016)... CA (PRWEB) , ... December 07, 2016 , ... ... wastewater treatment and resource recovery solutions for industrial facilities, today announced that one ... be the first to use Cambrian’s novel water-energy purchase agreement (WEPA). Under the ...
Breaking Biology Technology: