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Cystic Fibrosis Lung Infections Frequently Involve Bacteria Transmitted Between Humans

NEW YORK (GenomeWeb) – Many of the multidrug-resistant Mycobacterium abscessus bacteria that cause lung infections in individuals with cystic fibrosis seem to be acquired by direct or indirect person-to-person transmission rather than from the broader environment, a new study suggests.

An international team led by investigators in the UK sequenced almost 1,100 Mycobacterium isolates from 517 individuals with cystic fibrosis, using comparative genomics and phylogeny to trace the sources of the isolates and relationships between them. Results of the analysis, published online today in Science, indicate that M. abscessus spreads frequently between individuals with the help of aerosols or by hitching a ride on inanimate surfaces or objects such clothing, skin, and hair.

In their follow-up cell line and mouse model experiments, the researchers found evidence for enhanced virulence in M. abscessus. Based on these results, they have started searching for potential drug targets in these microbes and coming up with strategies to address gaps in infection control strategies.

"[N]ow that we know the extent of the problem and are beginning to understand how the infection spreads, we can start to respond," co-corresponding author Julian Parkhill, a researcher at the Wellcome Trust Sanger Institute, said in a statement. "Our work has already helped inform infection control policies and provides the means to monitor the effectiveness of these."

Unlike other microbes in the Mycobacterium genus, M. abscessus is not associated with tuberculosis infections, the team noted. Even so, the bug has been implicated in very serious lung infections in cystic fibrosis patients and other individuals with lung inflammation, leading to dangerous lung damage.

To get a glimpse at transmission and potential sources of infection for individuals with cystic fibrosis, the researchers did whole-genome sequencing on 1,080 M. abscessus isolates from 517 individuals treated at clinics in the UK.

From these data, they identified three M. abscessus sub-species: M. a. abscessus, present in 730 isolates; 256 isolates with the M. a. massiliense sub-species; 91 M. a. bolletii isolates; and three isolates with multiple M. abscessus sub-species.

Unlike the genetically diverse M. abscessus isolates described in individuals with cystic fibrosis in the 1990s or 2000s, which fit a pattern consistent with infection from microbe sources in soil or water, the newly sequenced isolates contained groups of M. abscessus that were genetically related to one another.

When the team analyzed the genomes alongside available sequences from sites around the world, for example, it did see some deeply divergent isolates that seemed to stem from environmental sources. But after removing isolates clustered at just one clinic that might have been contracted from the same environmental source, the researchers found that almost three-quarters of isolates clustered in ways that were consistent with person-to-person transmission.

Samples from 11 cystic fibrosis cases contained M. a. massiliense isolates that appeared to be related to one another, for example. Other clusters contained genetically similar M. a. abscessus isolates. 

The team noted that the types of shared genetic patterns detected in these clusters seemed to fit with known social interactions, epidemiological data, and known exposures in hospital. Rather than direct transmission, however, the results often appeared to fit with transfer via infected surfaces or aerosols.