# From colonisation to chronicity: adaptation of Mycobacterium abscessus in the cystic fibrosis lung environment

## TL;DR

This study shows how Mycobacterium abscessus adapts to the cystic fibrosis lung over time, making infections harder to treat.

## Contribution

The paper presents new evidence of pathoadaptation in M. abscessus through phenotypic and proteomic changes in clinical isolates.

## Key findings

- Late isolates showed increased host cell attachment and intracellular survival in macrophages.
- Proteomic changes in late isolates included proteins related to intracellular survival and antibiotic resistance.
- Adaptation was observed in isolates from three cystic fibrosis patients over 33 to 295 days.

## Abstract

M. abscessus isolates change in phenotype over time of colonisation. Upper panel highlights the timelines between the early isolate and the later isolate in each pair. Lower panel highlights changes observed between isolate pairs. Changes marked with green arrows were shown by phenotypic assays and proteomic data while changes marked with pink text were identified from proteomic data only. Changes in biofilm formation, colony morphology and sliding motility were not seen in this data set but have been identified previously in clinical isolates.

Chronic infection by opportunistic pathogens is a major contributor to mortality in people with cystic fibrosis (CF). These infections are caused by antimicrobial-resistant pathogens such as the emerging pathogen, Mycobacterium abscessus, a nontuberculous mycobacteria which causes recalcitrant infections with high resistance to antibiotics. M. abscessus adapts over time of colonisation to the conditions in the CF lung, hampering effective treatment. The mechanisms underlying this pathoadaptation are poorly understood and are critical for the development of future therapies. Sequential isolate pairs of M. abscessus from three people with CF were examined for adaptive changes over time of infection. These isolate pairs range in time span from 33 to 295 days. Genomic analysis confirmed that these isolate pairs were clonal. The late infection isolates showed increased host cell attachment to CF bronchial epithelial cells, and one late isolate showed increased intracellular survival in macrophages, indicative of potential adaptation to the CF lung environment. Late isolates also showed changes in their proteomes, including changes in abundance of proteins with roles in intracellular survival and antibiotic resistance. Overall, it is clear that M. abscessus can adapt to the CF lung environment and improve its ability to interact with host cells.