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 promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital

nachricht Stem cell transplants: activating signal paths may protect from graft-versus-host disease
20.04.2017 | Technische Universität München

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: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

Im Focus: Quantum-physical Model System

Computer-assisted methods aid Heidelberg physicists in reproducing experiment with ultracold atoms

Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...

Im Focus: Glacier bacteria’s contribution to carbon cycling

Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.

A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

New quantum liquid crystals may play role in future of computers

21.04.2017 | Physics and Astronomy

A promising target for kidney fibrosis

21.04.2017 | Health and Medicine

Light rays from a supernova bent by the curvature of space-time around a galaxy

21.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>