New research shows that bacteria aggregate to form biofilms in both acute and chronic lung infections. The researchers say that the discovery is a paradigm shift and provides insight into improving treatment for people with such diseases as cystic fibrosis.
Pathogenic bacteria that colonise a person’s lungs form a biofilm that protects the bacteria against the immune response.
New research in Denmark shows for the first time that these bacteria in an acute lung infection largely act similarly to the bacteria in chronic lung infections, such as those among people with cystic fibrosis.
The research also shows the differences in bacterial architecture between acute and chronic lung infections and suggests possible ways of tackling chronic lung infections to make them more susceptible to antibiotics that can eradicate the bacteria.
“A basic paradigm of human infection has been that rapidly growing planktonic bacteria cause acute bacterial infections whereas slow-growing biofilms cause chronic infections. Instead, they primarily differ in metabolic rates and not bacterial architecture. This also requires action to obtain tools to treat the chronic and dangerous lung infections among people with cystic fibrosis,” explains the first author, Mette Kolpen, Postdoctoral Fellow, Department of Clinical Microbiology, Rigshospitalet, Copenhagen.
The research, which has been published in Thorax, was carried out in collaboration with researchers from Costerton Biofilm Center at the University of Copenhagen, Rigshospitalet, North Zealand Hospital Hillerød and Georgia Institute of Technology, Atlanta, Georgia, USA.
Lack of oxygen makes bacteria dormant
When bacteria form biofilms, they secrete many proteins and other substances that create a mucus layer the bacteria can colonise where they are protected against the immune cells and antibiotics. The bacteria are especially difficult to combat deep inside the mucus layer.
Researchers in Denmark discovered this property of bacteria 40 years ago, and later researchers discovered that it characterises the bacteria that colonise the lungs of people with cystic fibrosis.
In addition to protecting the bacteria in the mucus layer, the immune system uses oxygen in expending energy to attack the bacteria, which makes the environment around the biofilm extremely oxygen-poor. The bacteria become dormant and do not grow.
“This is a problem because many of the ways of killing bacteria target bacterial growth. If the bacteria do not grow, antibiotics will not kill them,” says Mette Kolpen.
Bacteria also create biofilm during acute infections
So far, researchers have assumed that only bacteria in chronic lung infections form biofilms, but this paradigm is about to be changed.
In the new study, the researchers compared sputum samples from 14 people with cystic fibrosis with those from 29 people with acute community-acquired pneumonia.
Surprisingly, the bacteria formed biofilms in both chronic and acute infections.
The difference between the two types of infections was not the presence or absence of biofilms but that the bacteria have higher metabolic activity in acute infections. Further, the bacteria created more biomass in acute infections than in chronic infections because they grew more rapidly.
“We examined all the scientific literature, and we could not any studies of biofilm formation in acute lung infections. The research assumed that acute lung infections comprise individual planktonic cells that do not aggregate into a biofilm, so showing that they actually do is completely new,” explains a main author, Thomas Bjarnsholt, Professor, Costerton Biofilm Center, University of Copenhagen.
Oxygen to kill bacteria
This discovery has great perspectives for treating people with either acute or chronic lung infections.
Acute pneumonia is still relatively easy to eliminate using antibiotics that target growing bacteria because they are still growing in acute lung infections.
Getting the bacteria in the biofilm to grow rapidly in chronic infections might make them vulnerable to antibiotics and thereby able to be killed.
With this in mind, the researchers see opportunities for a completely new approach to treating bacterial infections among people with such diseases as cystic fibrosis.
Since a lack of oxygen inhibits bacterial growth, the bacteria should be exposed to oxygen, because in theory it will make them grow again and thereby become susceptible to antibiotics.
The researchers have already carried out the initial experiments of exposing bacteria to oxygen in the biofilms present in chronic infections, and the results have been promising.
One option is to treat people with cystic fibrosis with hyperbaric oxygen in a special chamber. The same treatment approach is used for people infected with flesh-eating bacteria.
“Our experiments have shown that exposing the bacteria in the biofilm to considerable oxygen can make them sensitive to antibiotics again. This enabled us to kill bacteria that were otherwise very difficult to eliminate. The next step, of course, will be to test this on humans. So far, however, there are indications that combining oxygen and antibiotics may reduce chronic lung infections among people with cystic fibrosis,” concludes Mette Kolpen.