A possible key to deadly pneumonia
A common cause of pneumonia can kill by causing bleeding in the lungs, researchers said Thursday in a finding that might explain why antibiotics fail to save many patients.
They found that the bacterium Streptococcus pneumoniae secretes a toxin that causes severe bleeding in the lungs in some patients, killing them within days.
The toxin is unaffected by antibiotics, which explains why the drugs often fail to save patients, the researchers reported in the journal Immunity. In fact, antibiotics kill bacteria by cutting them open -- releasing even more of the toxin.
“What we found is a possible mechanism and a possible solution for a very lethal pneumonia,” said Dr. Jian-Dong Li, a professor of microbiology and immunology at the University of Rochester Medical Center in New York who worked on the study.
“The power of understanding this mechanism is that it not only suggests how better to treat this disease, but also that we should think twice about whether standard drug treatments are doing more harm than good.”
S. pneumoniae infects the upper respiratory tract, causing pneumonia, meningitis and ear infections in the elderly and young children. Before a vaccine was introduced in 2000, there were 500,000 cases of pneumococcal pneumonia every year in the United States, with up to 40,000 of them serious.
Serious pneumonia killed up to 100 children every year and thousands of elderly people.
Many experts assumed that inflammation killed patients. As with any bacteria or virus, the body’s immune system activates to repel the invader, but in some patients this reaction becomes too strong and can be fatal.
“Many patients die at a very early time point -- 48 hours or so, but less than 72 hours. People noticed this but they didn’t know why,” Li said.
His team studied the bacteria, first in lab dishes and then in mice. They looked at a toxin known to be produced by the bacteria, called pneumolysin.
It was known to lyse, or break open cells; Li’s team found this also caused widespread bleeding in lung tissue. Tests on tissue from fatally stricken humans confirmed this.
“When you look at the pathology of the lung, we found bleeding everywhere in the lung. That is a key point,” Li said.
Li’s team found a possible antidote, a protein called plasminogen activator inhibitor 1 or PAI-1. The university has licensed its use to battle pneumococcal disease. Li thinks spraying it into the breathing passages of patients may counteract the action of pneumolysin.
“The next step will be to design a small molecule, a protein fragment, that can mimic PAI-1, which would be easier to deliver in the lungs, more effective and have fewer side effects,” Li said.
