Nav: Home

New study overturns orthodoxy on how macrophages kill bacteria

April 27, 2009

CHAMPAIGN, Ill. -- For decades, microbiologists assumed that macrophages, immune cells that can engulf and poison bacteria and other pathogens, killed microbes by damaging their DNA. A new study from the University of Illinois disproves that.

The study, published in the journal PLoS ONE, shows that macrophages focus their most potent poisons, known as reactive oxygen species (ROS), on targets outside the cytoplasm.

Macrophages are voracious eaters that "swallow" cellular debris and invading organisms. They kill microbes with ROS. All aerobic cells inadvertently produce ROS that can, if left unchecked, damage DNA and other cellular components and cause cell death.

Bacteria and animal cells contain special enzymes, called superoxide dismutases, which neutralize an important ROS, called superoxide.

Macrophages have harnessed these lethal compounds, dumping large quantities of superoxide onto engulfed bacteria to kill them.

Although macrophages direct ROS against invading bacteria, Salmonella typhimurium, the microbe used in the study, is adept at evading these defenses. The most virulent strains of S. typhimurium can survive and even propagate inside macrophages, eventually emerging to infect more cells.

"It's been assumed that reactive oxygen species kill the bacteria by going into the cytoplasm and causing DNA damage," said medical microbiology professor James Slauch, who led the study. "You can find this idea over and over again in review articles and many immunological textbooks, but with no real data to back it up."

To test this hypothesis, Slauch and graduate student Maureen Craig looked at the superoxide dismutases that are part of the bacterial defense against ROS. There are two such enzymes in the cytoplasm of S. typhimurium, called SodA and SodB, and another, SodC, in the periplasm, the space between the bacteria's inner and outer membranes.

One way to understand the role of an enzyme is to see what happens when it is absent, so the researchers looked at mutant S. typhimurium that had the genes for SodA, SodB, or both enzymes, deleted. Deleting the gene for SodA seemed to make no difference, but the SodB mutants were less able to survive and cause disease in a mouse. The double mutants were even more impaired. They were much, much less likely to survive in the mouse than bacteria with only the SodB gene missing. These findings "offer genetic proof" that both enzymes "are involved in the same process," Slauch said.

The fact that the bacterial mutants were less likely to survive in a mouse did not prove, however, that the missing enzymes were protecting the bacteria from ROS generated in the mouse macrophages, Slauch said.

"You get the same result if you grow these mutants in the laboratory in aerobic conditions," he said.

Furthermore, the SodA/SodB mutant bacteria were profoundly weakened - even in a mouse that was unable to produce the potent ROS superoxide in its macrophages. These results suggest that the superoxide dismutases in the bacterial cytoplasm are most likely protecting the bacterium from its own, naturally occurring ROS, Slauch said.

In contrast, deleting the gene encoding the periplasmic superoxide dismutase, SodC, conferred the same defect regardless of whether the cytoplasmic SodA/SodB were present or absent, showing that its function is independent of the cytoplasm.

Moreover, strains lacking SodC were impaired only in the presence of superoxide produced in macrophages; there was no impairment in laboratory media or in mice lacking the ability to make superoxide.

This suggests that the superoxide and other reactive oxygen species are not making it from the macrophage into the bacterial cytoplasm, Slauch said.

"We conclude from all this data that the most sensitive target of ROS in the macrophages lies outside the cytoplasm," Slauch said. "We don't know what that target is, but it's clearly not in the cytoplasm."
-end-
Editor's notes: To reach James Slauch, call: 217-244-1956; e-mail: slauch@illinois.edu.

To view or subscribe to the RSS feed for Science News at Illinois, go to: http://webtools.uiuc.edu/rssManager/608/rss.xml.

University of Illinois at Urbana-Champaign

Related Bacteria Articles:

Conducting shell for bacteria
Under anaerobic conditions, certain bacteria can produce electricity. This behavior can be exploited in microbial fuel cells, with a special focus on wastewater treatment schemes.
Controlling bacteria's necessary evil
Until now, scientists have only had a murky understanding of how these relationships arise.
Bacteria take a deadly risk to survive
Bacteria need mutations -- changes in their DNA code -- to survive under difficult circumstances.
How bacteria hunt other bacteria
A bacterial species that hunts other bacteria has attracted interest as a potential antibiotic, but exactly how this predator tracks down its prey has not been clear.
Chlamydia: How bacteria take over control
To survive in human cells, chlamydiae have a lot of tricks in store.
Stress may protect -- at least in bacteria
Antibiotics harm bacteria and stress them. Trimethoprim, an antibiotic, inhibits the growth of the bacterium Escherichia coli and induces a stress response.
'Pulling' bacteria out of blood
Magnets instead of antibiotics could provide a possible new treatment method for blood infection.
New findings detail how beneficial bacteria in the nose suppress pathogenic bacteria
Staphylococcus aureus is a common colonizer of the human body.
Understanding your bacteria
New insight into bacterial cell division could lead to advancements in the fight against harmful bacteria.
Bacteria are individualists
Cells respond differently to lack of nutrients.

Related Bacteria Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#529 Do You Really Want to Find Out Who's Your Daddy?
At least some of you by now have probably spit into a tube and mailed it off to find out who your closest relatives are, where you might be from, and what terrible diseases might await you. But what exactly did you find out? And what did you give away? In this live panel at Awesome Con we bring in science writer Tina Saey to talk about all her DNA testing, and bioethicist Debra Mathews, to determine whether Tina should have done it at all. Related links: What FamilyTreeDNA sharing genetic data with police means for you Crime solvers embraced...