Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Glowing bacteria show researchers how an anti-flu-virus drug may prevent bacterial pneumonia

10.03.2003


Viral enzyme ’clear cuts’ forest of protective molecules on lung cells in mice; blocking that enzyme reduces illness and incidence of death from subsequent infection by Streptococcus pneumoniae



Investigators at St. Jude Children’s Research Hospital have shown in mice how the potentially deadly cooperation between influenza virus and bacterial pneumonia infections can be foiled, even if treatment is delayed and flu virus levels in the lung have peaked.

The St. Jude team showed that the flu virus enzyme neuraminidase (NA) strips lung cells of their protective forest of molecules called sialic acid. The unprotected cells are then vulnerable to subsequent infection with Streptococcus pneumoniae bacteria. But treatment of the mice with the NA-inhibitor drug ostelamivir blocked the activity of flu virus NA and offered significant protection against pneumonia. The study’s findings appear in the March 15 issue of the Journal of Infectious Diseases.


"We previously showed that when Streptococcus pneumoniae was given to mice seven days after they had been infected with flu virus, the mortality was extremely high," said Jonathan McCullers, MD, the lead author of the report. "Our current study using tissue in lab dishes, as well as live mice, showed that viral NA is the key to this deadly synergy between flu virus and pneumonia bacteria. The streptococcus bacteria also have NA," McCullers said, "but it is much less efficient than the viral enzyme in cutting away at the lung cell’s sialic acid barrier."

The St. Jude finding is important because a combined infection with influenza and pneumonia is the sixth leading cause of all deaths worldwide, and is the top cause of death due to an infection, according to McCullers assistant member in the Department of Infectious Diseases at St. Jude. Moreover, the overall death rate associated with pneumonia and influenza increased by 59% between 1979 and 1994, according to a 1996 report in the Journal of the American Medical Association.

"The flu virus targets the sialic acid molecules on the lung cell membrane surface so it can get inside the lung cell and reproduce," McCullers said. "After the virus multiplies inside the cell, the new viruses cut through the sialic acid on the way out."

"By blocking the virus NA we protect the sialic acid molecules covering the lung cells," says McCullers. "That leaves the pneumonia bacteria stranded outside the cells and gives the immune system time to destroy them before they can cause respiratory disease."

In the study, one group of mice received prophylactic (protective) doses of oseltamivir for five days, beginning four hours before being infected with flu virus. Another group got oseltamivir for five days starting 48 hours after being infected with flu.

Mice that received delayed treatment lost weight and had greatly increased levels of virus in their lungs by the time they received oseltamivir. However, these mice still had significant protection against subsequent infection by streptococcus bacteria compared to control mice that received no treatment.

"The key to significantly reducing the rate of death in these mice was not reducing virus levels or maintaining weight," McCullers explains. "What was important was blocking the virus NA enzyme with oseltamivir and preserving the protective sialic acid molecules."

The St. Jude team also studied the effect of oseltamivir on bacterial pneumonia using live mice infected with genetically modified streptococcus. These modified bacteria were engineered to carry on a light-producing chemical reaction--the same chemical reaction used by fireflies. The light, too faint for humans to see, passed through the skin of the mice and was picked up by a special camera.

In mice given flu virus and then the "glowing" streptococcus but no oseltamivir, the camera captured images of extensive bacterial infections throughout the thorax--the part of the body containing the lungs. In mice that also received oseltamivir as a delayed treatment after infection with flu virus, the light emitted from the lungs was less intense and not localized in specific areas. This suggested that the immune system of the infected mice was able to kill many of the bacteria that were "stranded" outside the cell membrane in oseltamivir-treated animals.

Untreated mice developed pneumonia earlier than treated mice and died. In treated mice, even when infection spread, the progression of the disease was slower than in untreated mice, and up to half of the treated animals survived.

When the researchers studied the effect of oseltamivir using human lung cells in a dish, they found that the drug blocked the binding of streptococcus to these cells by interfering with NA, similar to the findings in mice.

The article’s co-author is Rhodes College pre-med student Kimberly A. Bartmess, who works in Dr. McCullers’ lab as a part of the St. Jude – Rhodes Summer Plus Program.


###
This project was supported by the National Institute of Allergy and Infections Diseases at the National Institutes of Health, a Cancer Center Support Grant and ALSAC.

St. Jude Children’s Research Hospital
St. Jude Children’s Research Hospital, in Memphis, Tennessee, was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for catastrophic diseases of childhood. The hospital’s work is supported through funds raised by ALSAC. ALSAC covers all costs not covered by insurance for medical treatment rendered at St. Jude Children’s Research Hospital. Families without insurance are never asked to pay. For more information, please visit www.stjude.org.

Bonnie Cameron | EurekAlert!
Further information:
http://www.stjude.org/

More articles from Health and Medicine:

nachricht A whole-body approach to understanding chemosensory cells
13.12.2017 | Tokyo Institute of Technology

nachricht Research reveals how diabetes in pregnancy affects baby's heart
13.12.2017 | University of California - Los Angeles Health Sciences

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

A whole-body approach to understanding chemosensory cells

13.12.2017 | Health and Medicine

Water without windows: Capturing water vapor inside an electron microscope

13.12.2017 | Physics and Astronomy

Cellular Self-Digestion Process Triggers Autoimmune Disease

13.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>