Navigation Links
Research could lead to new non-antibiotic drugs to counter hospital infections

Lack of an adequate amount of the mineral phosphate can turn a common bacterium into a killer, according to research to be published in the April 14, 2009, issue of the Proceedings of the National Academies of Science. The findings could lead to new drugs that would disarm the increasingly antibiotic-resistant pathogen rather than attempting to kill it.

Pseudomonas aeruginosa is one of the most serious hospital-acquired pathogens. A common cause of lung infections, it is also found in the intestinal tract of 20 percent of all Americans and 50 percent of hospitalized patients in the United States.

It is one of the hundreds of bacteria that colonize the human intestinal tract, usually causing no apparent harm. It might even be beneficial to its host. Once the host is weakened by an illness, surgical procedure or immunosuppressive drugs, however, P. aeruginosa can cause infection, inflammation, sepsis and death.

Why P. aeruginosa can suddenly turn on its host has eluded researchersuntil now. Scientists have long known that after an operation or organ surgery, levels of inorganic phosphate fall. The authors of the PNAS paper, led by scientists at the University of Chicago, hypothesized that phosphate depletion in the stressed intestinal tract signals P. aeruginosa to become lethal.

To test this theory, they let worms (Caenorhabditis elegans) feed on "lawns" of P. aeruginosa and Escherichia coli grown in both low-phosphate and high-phosphate media. Only the worms that ate P. aeruginosa with low levels of phosphate died. The researchers dubbed the phenomenon "Red Death" since unexpected large red spots appeared on the worms before they died.

"These findings provide novel insight into the mechanisms by which P. aeruginosa is able to shift from indolent colonizer to a lethal pathogen when present in the intestinal tract of a stressed host," said Alexander Zaborin, lead author of the study and a research professional at the University of Chicagos Department of Surgery.

"It's almost as if the bacterium sense when to strike," said John Alverdy, corresponding author of the study and professor of surgery at the University of Chicago Medical Center. "That should come as no surprise since the bacteria are smart, having been around for 2 billion years."

Bacteria seek phosphate as an important nutrient, Alverdy explained. And rather than try to look for it in the blood steam of critically ill patients, where they would encounter armies of antibiotics and disease-fighting white blood cells, they find it inside organ tissues. This process damages and sometimes even kills their host.

Experiments with mice showed that the harm caused when P. aeruginosa becomes activated to express lethal toxins inside the intestinal tract can be mitigated by providing excess phosphate.

The research findings could lead to a pharmaceutical product that would restore healthy phosphate levels in the intestines of such stressed and compromised patients, Alverdy said.

"Antibiotics attempt to kill harmful bacteria, but in the process they often kill beneficial bacteria," said Olga Zaborina, an associate professor at the University of Chicagos Department of Surgery and another key researcher in this study. "A more sensible approach to fighting infectious diseases may be to try to understand the circumstances that provoke a microbe to cause harm in the first place and then find ways to pacify them without destroying them."

Containment on a case-by-case basis might be a more effective and longer-lasting strategy than a scorched earth policy, Alverdy said. Midway Pharmaceuticals, which Alverdy founded in 2005, is developing a pipeline of non-antibiotic compounds that contain or disarm specific bacteria.

Appreciation of the subtle mechanisms in pathogens that colonize the intestinal tract of critically ill patients has important implications for the design of phosphate-based compounds that might prevent P. aeruginosa and other pathogens from turning lethal, the researchers concluded.

Despite the use of powerful antibiotics, P. aeruginosa remains a leading cause of sickness and death among hospitalized patients who have undergone surgery or have reduced immunity. If the bacterium attacks critical body organs such as the lungs, urinary tract and kidneys, it is likely to be fatal. P. aeruginosa thrives on moist surfaces, so it is often found on catheters, causing cross-hospital infections. It is also implicated in a common form of dermatitis associated with poor hygiene and inadequate maintenance of hot tubs.


Contact: Greg Borzo
University of Chicago Medical Center

Related biology news :

1. Research shows skeleton to be endocrine organ
2. Newly created cancer stem cells could aid breast cancer research
3. Dominant cholesterol-metabolism ideas challenged by new research
4. Researchers identify proteins involved in new neurodegenerative syndrome
5. Texas researchers and educators head for Antarctica
6. MGH researchers describe new way to identify, evolve novel enzymes
7. University of Pennsylvania researchers develop formula to gauge risk of disease clusters
8. University of Oregon researcher finds that on waters surface, nitric acid is not so tough
9. U of MN researchers discover noninvasive diagnostic tool for brain diseases
10. U of Minnesota researchers discover noninvasive diagnostic tool for brain diseases
11. Story ideas from the Journal of Lipid Research
Post Your Comments:
(Date:5/16/2016)... YORK , May 16, 2016   EyeLock ... solutions, today announced the opening of an IoT Center ... to strengthen and expand the development of embedded iris ... an unprecedented level of convenience and security with unmatched ... authenticate one,s identity aside from DNA. EyeLock,s platform uses ...
(Date:4/28/2016)... BANGALORE, India , April 28, 2016 /PRNewswire/ ... product subsidiary of Infosys (NYSE: INFY ), and ... global partnership that will provide end customers with ... banking and payment services.      (Logo: ... area for financial services, but it also plays a fundamental ...
(Date:4/19/2016)... 2016 The new GEZE SecuLogic ... web-based "all-in-one" system solution for all door components. It ... the door interface with integration authorization management system, and ... The minimal dimensions of the access control and the ... installations offer considerable freedom of design with regard to ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... NC (PRWEB) , ... June 27, 2016 , ... ... just published their findings on what they believe could be a new and ... of the new research. Click here to read it now. , ...
(Date:6/27/2016)... BOSTON , June 27, 2016   Ginkgo ... biology to industrial engineering, was today awarded as ... a selection of the world,s most innovative companies. ... at scale for the real world in the ... organism engineers work directly with customers including Fortune ...
(Date:6/23/2016)... , ... June 23, 2016 , ... ... release of its second eBook, “Clinical Trials Patient Recruitment and Retention Tips.” Partnering ... retention in this eBook by providing practical tips, tools, and strategies for clinical ...
(Date:6/23/2016)... , June 23, 2016 Houston ... with the Cy-Fair Sports Association to serve as ... the agreement, Houston Methodist Willowbrook will provide sponsorship ... and connectivity with association coaches, volunteers, athletes and ... with the Cy-Fair Sports Association and to bring ...
Breaking Biology Technology: