cronoclone
Intraindividual variation of M. abscessus
Introduction: M. abscessus is a multi-drug resistant rapid-growing mycobacterium that causes difficult to treat infections. Especially, patients with predisposing lung conditions, such as cystic fibrosis, are the ones most at risk. It has also been involved in nosocomial transmission during surgical procedures. However, the existence of so-called dominant circulating clones that exist globally and are associated with higher mortality and morbidity have lead to the assumption that inter-human transmission (direct or via fomites) takes place in these NTM. It has been stipulated that this NTM undergoes similar evolutional changes as M. tuberculosis complex before becoming a exclusively pathogenic mycobacterium.
Objectives: This study will implement state-of-the-art DNA sequencing and phenotyping technologies for operational research on NTM in CF to address the following hypotheses: i) Whole genome sequencing (WGS) of
sequential M. abscessus isolates from single patients can identify the occurrence of genomic polymorphisms in NTM associated with virulence and drug resistance, and provide comprehensive typing data to identify transmission. ii) Phenotypic drug susceptibility testing (pDST) can be used to validate genotype/phenotype relations for specific NTM strains and provide functional data on clinical drug susceptibility breakpoints. iii) Comprehensive analysis of sequential NTM isolates from single patients by WGS and pDST will improve prediction of clinical impact of NTM-positive cultures in individual patients.
Expected benefit for CF patients:
- New insights into patient-to-patient transmission, evolution of virulence and resistance over time and the correlation of genotype, phenotype and clinical outcome
- New evidence to design personalized treatment regimens for CF patients with NTM infections and new directions for future NTM research
Methods: Clinical and epidemiological data-analysis, whole genome sequencing, genotypic drug susceptibility testing.
Status: Data analysis currently ongoing
Image Credit: REM/SEM analysis, M. abscessus rough phenotype, F.V. Sotomayor, T. Gutsmann and S. Homolka.