Study reveals rapid evolution and global spread of Pseudomonas aeruginosa

Pseudomonas aeruginosa, an environmental bacterium that can cause devastating multi-drug-resistant infections, particularly in people with underlying lung conditions, has rapidly evolved and subsequently spread across the globe over the past 200 years, likely driven by changes in human behavior, a new study finds.

The work appears in the magazine Science.

P. aeruginosa is responsible for over 500,000 deaths per year worldwide, of which over 300,000 are associated with antimicrobial resistance (AMR). People with conditions such as COPD (smoking-related lung injury), cystic fibrosis (CF) and non-CF bronchiectasis are particularly susceptible.

How P. aeruginosa evolved from an environmental organism to a specialized human pathogen was previously unknown. To investigate, an international team led by scientists from the University of Cambridge examined DNA data from nearly 10,000 samples taken from infected individuals, animals, and environments around the world.

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 one another. Remarkably, they found that nearly seven out of 10 infections are caused by just 21 genetic clones, or “branches” of the family tree that have rapidly evolved (acquiring new genes from neighboring bacteria) and then spread globally over the past 200 years.

This spread probably occurred because people moved to densely populated areas, where air pollution made our lungs more susceptible to infection and there was a greater chance of infection spreading.

These epidemic clones have an intrinsic preference for infecting certain types of patients, with some favoring CF patients and others non-CF individuals. It turns out that the bacteria can exploit a previously unknown immune defect in people with CF that allows 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 system of CF patients means that once the macrophage has gobbled up P. aeruginosa, it can’t get rid of it.

After infecting the lungs, these bacteria evolve in different ways to become even more specialized for a particular lung environment. The result is that certain clones can be transmitted within CF patients and other clones within non-CF patients, but almost never between CF and non-CF patient groups.

Professor Andres Floto, Director of the UK Cystic Fibrosis Innovation Hub at the University of Cambridge and the Royal Papworth Hospital NHS Foundation Trust, and lead author of the study, said: “Our research into Pseudomonas has taught us new things about the biology of cystic fibrosis and revealed important ways in which we can improve 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 CF patients, 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 individual to be on an open ward with someone who is potentially very vulnerable.

“We are incredibly lucky at Royal Papworth Hospital. We have single rooms here and have developed and evaluated a new air handling system to reduce the amount of bacteria in the air and protect all patients.”

Dr Aaron Weimann from the Victor Phillip Dahdaleh Heart & Lung Research Institute at the University of Cambridge, and first author of the study, said: “It is remarkable how quickly these bacteria can evolve and become epidemic, and how they can specialise in a specific lung environment. We really need systematic, proactive screening of all at-risk patient groups to detect and hopefully prevent the emergence of more epidemic clones.”