Pseudomonas aeruginosa —an environmental bacterium that can cause devastating multidrug-resistant infections, particularly in people with underlying lung diseases—evolved rapidly and then spread globally over the past 200 years, likely driven by changes in human behavior, according to a new study.
P. aeruginosa It is responsible for more than 500,000 deaths a year worldwide, of which more than 300,000 are associated with antimicrobial resistance (AMR). People with conditions such as COPD (smoking-related lung damage), cystic fibrosis (CF) and non-CF bronchiectasis are particularly susceptible.
As P. aeruginosa Until now, it was not known how the virus evolved from an environmental organism into a specialized human pathogen. To investigate, an international team led by scientists at the University of Cambridge examined DNA data from nearly 10,000 samples taken from infected individuals, animals and environments around the world. Their results are published today in Science
By mapping the data, the team was able to create phylogenetic trees (family trees) that show how the bacteria in the samples are related to each other. Remarkably, they found that nearly seven out of ten infections are caused by just 21 genetic clones, or “branches” of the family tree, which have evolved rapidly (by acquiring new genes from neighboring bacteria) and then spread globally over the past 200 years. This spread most likely occurred as a result of people starting to live in densely populated areas, where air pollution made our lungs more susceptible to infections and where there was more opportunity for infections to spread.
These epidemic clones have an intrinsic preference for infecting certain types of patients, with some preferring patients with cystic fibrosis and other individuals without cystic fibrosis. It turns out that the bacteria can exploit a previously unknown immune defect in people with cystic fibrosis, allowing them to survive inside macrophages. Macrophages are cells that “eat” invading organisms, breaking them down and preventing the infection from spreading. But a previously unknown defect in the immune systems of cystic fibrosis patients means that once the macrophage “swallows” P. aeruginosacan’t get rid of it.
Once they have infected the lungs, these bacteria evolve in different ways to further specialize in a particular lung environment. The result is that certain clones can be transmitted between patients with cystic fibrosis and other clones between patients without cystic fibrosis, but almost never between groups of patients with cystic fibrosis and patients without cystic fibrosis.
Professor Andrés Floto, Director of the Cystic Fibrosis UK Innovation Centre at the University of Cambridge and Royal Papworth Hospital NHS Foundation Trust, and senior author of the study, said: “Our research on Pseudomonas has taught us new things about the biology of cystic fibrosis and revealed important ways in which we could enhance immunity against invading bacteria in this and potentially other conditions.
“From a clinical perspective, this study has revealed important information about Pseudomonas. The focus has always been on how easily this infection can spread between patients with cystic fibrosis, but we have shown that it can also spread with worrying ease between other patients. This has very important implications for infection control in hospitals, where it is not uncommon for an infected person to be in an open ward with someone who is potentially very vulnerable.
“We are very lucky at Royal Papworth Hospital to have single rooms and have developed and tested a new air handling system to reduce the amount of airborne bacteria and protect all patients.”
Dr Aaron Weimann, from the Victor Phillip Dahdaleh Heart and Lung Research Institute at the University of Cambridge and first author of the study, said: “It’s amazing to see how quickly these bacteria evolve and can become epidemic, and how they can specialise for a particular lung environment. We really need systematic, proactive screening of all at-risk patient groups to detect and hopefully prevent further epidemic clones from emerging.”
The research was funded by Wellcome and the UK Cystic Fibrosis Trust.