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Trash disguise helps Listeria kill slowly
WASHINGTON (Reuters) -- By disguising one of its destructive proteins as "trash," the Listeria bacteria responsible for thousands of cases of food poisoning each year manages to infect its host without making it too sick, researchers said on Thursday.
The bacteria hijacks various mechanisms of the cells it infects to keep itself safe and to keep its own destructive proteins from going too far, a team at the University of California, Berkeley, reported.
"It really is quite amazing over millions of years how clever microorganisms are," Daniel Portnoy, a microbiologist who led the study, said in a telephone interview.
"A pathogen doesn't really need to have multitudes of genes. With relatively little genetic material, you can take advantage of your host."
Listeria bacteria, which cause an estimated 2,500 cases of serious illness and 500 deaths every year in the United States, are found in soft cheeses, hot dogs and other popular foods. They take hold in the body when immune cells called phagocytes do what they are supposed to do and eat them.
The phagocyte puts the bacteria into its "stomach," called a vacuole, where they usually are destroyed. But sometimes the Listeria can survive long enough to get out.
"They use this protein that actually causes the vacuole to rupture," said Portnoy, whose findings are reported in Friday's issue of the journal Science. "They then get into the guts of the cell. One bacterium becomes 2, 4, 8." Within five hours, the cell is bursting with Listeria bacteria.
"There's going to be more than 100 bacteria per cell and the cell is still happy," Portnoy said. "They are able to grow but without being toxic. That is their trick."
The mystery has been how this hole-punching protein, called listeriolysin O, avoids rupturing the outside cell wall, killing the cell and spilling the bacteria out where other immune cells can get them.
Portnoy and fellow researchers compared listeriolysin O to a similar pore-forming toxin called perfringolysin O, taken from the Clostridium perfringens bacteria that cause gangrene.
If they substituted perfringolysin O for listeriolysin O, the genetically engineered bacteria did indeed destroy their host cell and got mopped up by the immune system.
Looking at the genes of the proteins, the researchers found that listeriolysin O has a little tag, found in a range of organisms from yeast to humans, that marks its as trash.
"One interpretation is that it is saying 'I am trash -- cut me up'," Portnoy said.
So the hole-punching protein works just long enough to let the bacteria out of the vacuole, and is broken down before it can do any more damage. "They don't want to kill cells," Portnoy said.
If all goes well for the bacteria, it causes the cell to form a small fingerlike projection called a pseudopod, which can carry the bacteria into a neighboring cell.
The system works well for the bacteria and for the infected host, Portnoy said. "We all eat Listeria every day or certainly a few times a year, and yet there are only a few cases of listeriosis," he said.
Researchers are not sure why such microbes occasionally make people sick.
People who have weak immune systems -- pregnant women, the elderly and the very young -- are most likely to get sick when infected. Portnoy and others believe that perhaps an overreaction of the immune system's inflammatory processes may be responsible for illness.
But it is a serious problem. "One-third of the people on this planet who die are dying of intracellular pathogens, be it AIDS, tuberculosis or malaria," he said.
"There are no effective vaccines for any of these diseases," he added. Understanding Listeria may help scientists understand how to fight other microbes.
Signs of listeriosis include fever, muscle aches, and sometimes nausea or diarrhea. If infection spreads to the nervous system, it can cause headache, stiff neck, confusion, loss of balance, or convulsions.
Copyright 2000 Reuters. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.
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