Smoking can really clog up the lungs, even for people who’ve never been near a cigarette. Turns out that smoking habits from the early 1900s are still inflicting damage—not on tobacco users or their families, but on people with cystic fibrosis.
Cystic fibrosis (CF) is a hereditary condition that makes afflicted people’s mucus thick and sticky. Their lungs become breeding grounds for bacteria that healthy people’s immune systems easily defeat. People with CF often take antibiotics to prevent lung infections, but antibiotics don’t kill everything. A bacterium called Mycobacterium abscessus (M. abscessus) is resistant to many common drugs, and it has become a plague in the CF community over the last couple of decades.
A few years ago, scientists began investigating how the plague originated. By analyzing M. abscessus genomes collected from people around the world, the researchers traced the bacterium’s spread over the last century. They found that decades before the 1950s—before medical advances let people with CF survive past infancy—M. abscessus was already spreading around the globe, and an old public health enemy was to blame. Smokers’ lungs created a reservoir where the pathogen could live and reproduce, a reservoir that quickly spilled over when people with cystic fibrosis began living into adulthood.
Making this unexpected connection required sequencing the full genomes of thousands of M. abscessus strains from around the world, and scientists who weren’t involved in the research say that the hard work paid off.
“It’s pretty clear—this finding,” said Vegard Eldholm, an infectious disease researcher at the Norwegian Institute of Public Health.
“It’s a really cool paper,” said Verity Hill, a molecular epidemiologist from University of Edinburgh. “Really elegant and really well thought out.”
Scientists used to think M. abscessus spent most of its time in the environment and that people with damaged lungs contracted infections when they were exposed to contaminated soil or water. This dogma changed five years ago when a group led by infectious disease researchers Julian Parkhill and Andres Floto showed that M. abscessus can spread from one person with CF to another—and that CF treatment centers were hotbeds for transmission.
The results came as a surprise. At the time, researchers didn’t know much about the genetics of M. abscessus. Parkhill and Floto set out to sequence the genomes of M. abscessus strains found in people who received treatment at a single CF center to see how much variation they’d find and whether that genetic variation correlated with virulence. They assumed that each infected person had contracted the pathogen from the environment independently, so the genomes would vary substantially. Instead, many of the genomes were similar or even identical. “We were really surprised to find that there was really strong evidence that these patients had transmitted it to each other,” Parkhill said.
But not all of the M. abscessus infections could be explained by spread within the treatment center. Some of the genomes were too similar to have been picked up from the environment, but too different to have come directly from other people at the center. So where did they originate?
A bigger study
“The answer to any question is always more data,” Parkhill said. His group sequenced the genomes of M. abscessus strains isolated from over 1,000 people from around the world—some with CF, some with other types of lung damage—to understand how the pathogen spreads.
Armed with a boatload of genetic sequences, “you build what is essentially a family tree,” said Hill, who uses similar techniques to track the spread of viruses. Bacteria that were genetically similar grouped together, like how siblings occupy the same branch of a family tree. Knowing approximately how often the M. abscessus genome gains a new mutation let the researchers add dates to the tree.
Around the 1960s, the tree turned bushy. M. abscessus began to mutate rapidly, leading to a dense web of branches. The timing correlates with the establishment of centers for CF treatments, which allowed people with CF to live past infancy and interact with each other. “You’re creating a niche for bacteria to live in—this niche of the lungs of people with CF—and also a transmission route,” Parkhill said. What’s good for people with CF is good for M. abscessus, so it makes sense that the pathogen took off in the middle of the century.
But the roots of the tree lay farther back in time, leading the researchers to wonder what drove the spread of M. abscessus before modern CF treatment was available, when most afflicted people died very young?
Drawing on human genetics
Parkhill knew that tobacco smokers are also susceptible to M. abscessus infections, and, coincidentally, his colleagues had published a study showing that cells from tobacco-associated cancers have characteristic genetic mutations. Parkhill wondered if he could detect these same mutations in M. abscessus.
“I really didn’t believe it would work,” he said. Because the mutational signature associated with smoking is subtle, his lab had to analyze hundreds of genomes to be confident that the signatures they found were true evidence of tobacco exposure and not just flukes. Each genome contains more DNA bases than the number of characters in Moby Dick, so the computer program the researchers wrote took days to chug through all the data. But, in the end, the tobacco mutational signature shone through the genetic noise. The group felt it had compelling data that smokers carry M. abscessus.
This study marks the first time researchers have used mutational analysis to identify environments a pathogen has lived in. “I wasn’t immediately convinced that this was something they were going to be able to prove,” Eldholm said. “But this mutational spectrum analysis is actually pretty convincing.”
“That sets a precedent,” Hill said. She suspects the study will inspire other microbiologists to perform similar analyses.
When researchers realized M. abscessus can spread between people with CF, it changed the way health care providers thought about preventing the disease. The new study shows that the danger of transmission is even more widespread. But knowledge creates options. Parkhill said: “The more we can identify [routes of] transmission, the more it can be shut down.”
Saima is a freelance science writer based in Somerville, Massachusetts. When she’s not writing, she enjoys biking around the city, learning photography, and practicing taekwondo.