The Taming of the Pathogen

The drug AZM disrupts the information flow between Pseudomonas bacteria

The drug, azithromycin (AZM), has been found to curb pathogenic bacteria. AZM combats bacteria in the Pseudomonas aeruginosa family, which can be especially dangerous for people with respiratory ailments. Scientists at the German Research Centre for Biotechnology (GBF) in Braunschweig have discovered that AZM prevents these bacteria from becoming aggressive and destructive. AZM blocks the mechanism used by the bacteria to "measure" how many of them there are in a particular environment. Unaware of their numbers and how strong they've already become, the pathogens, as a result, delay their big attack.
Pseudomonas aeruginosa can trigger persistent and troublesome lung infections. The bacteria can even become a serious and frequently deadly threat for people suffering from cystic fibrosis (CF), a congenital disease that adversely affects respiratory functions, impeding, for example, the clearing of the lungs of particles and bacteria embedded within the bronchial mucous. For Pseudomonas aeruginosa, the viscous lung secretions of CF patients are an ideal habitat. "Many people with this disease become infected with Pseudomonas aeruginosa and never get rid of it," explains GBF researcher, Dr. Susanne Häussler. "Pseudomonas aeruginosa for them is the most common cause of death." For many, catching this pathogen means having to live with it. "Antibiotics don't help," says Dr. Häussler, "because Pseudomonas becomes virtually entrenched in the thick bronchial mucous of CF patients."
AZM, which belongs to the macrolide group of drugs, is incapable of killing Pseudomonas aeruginosa, but helps to keep the pathogen relatively benign, preventing it from moving into a more antagonistic phase where it would begin attacking and destroying large sections of lung tissues - a circumstance that usually is fatal for cystic fibrosis patients.
The mechanisms involved in this process have now been clarified by Susanne Häussler and her research colleagues and published in the most recent issue of the Journal of Antimicrobial Agents and Chemotherapy. "AZM disrupts the bacteria's so-called quorum sensing mechanism," explains Dr. Häussler, "a mechanism used by them to determine their population density." Only when the bacteria have reached a certain population density they become virulent. They no longer appear satisfied to grow unnoticed, but switch instead into a more aggressive mode, directly confronting the human immune system. Häussler is confident that understanding this mechanism could help in the long term to search for new agents that combat chronic infections with Pseudomonas aeruginosa. "In many cases," says the GBF researcher, "it is nearly impossible to eradicate all the Pseudomonas bacteria found in the lung of a cystic fibrosis patient." "But," she adds, "we can stabilize a patient's condition and improve the chances if we look specifically for substances that disrupt the pathogen's quorum sensing abilities. And, if the immune system is given enough time, it has a chance to combat these less virulent bacteria. can in some cases combat the bacteria."

Additional Information for the Media

Original article: Y. Nalca, L. Jänsch, F. Bredenbruch, R. Geffers, J. Buer, S. Häussler: "Quorum Sensing antagonistic activities of Azithromycin in Pseudomonas aeruginosa PAO1: a global approach." Journal of Antimicrobial Agents and Chemotherapy, May 2006, Volume 50, Issue 5.
Photo material on this subject is available at: www.gbf.de/presseinformationen

Photo legend

The most common cause of death among people suffering from cystic fibrosis: Pseudomonas aeruginosa
Photograph: GBF/Rohde

“Tracking the communication pathways of Pseudomonas bacteria: GBF scientists Dr. Yusuf Nalca and Dr. Susanne Haeussler.
Photograph: GBF/Gramann”

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