Genetic diversification of persistent Mycobacterium abscessus within cystic fibrosis patients

Virulence

Claudia Grehn¹  Carsten Schwarz²  Patience Eschenhagen²  Jennifer Bender³  Astrid Lewin⁴  Elisabeth Kamal⁴  Hubert Schäfer⁴  Lei Mao⁵  Katja Winter⁶  Sandra Kaiser⁶  Torsten Semmler⁷ 

[1] Department of Pediatrics, Division of Pulmonology, Immunology and Intensive Care Medicine, Division of Cystic Fibrosis, Charité – Universitätsmedizin, Berlin, German;Klinikum Westbrandenburg, Campus Potsdam, Cystic Fibrosis Section, Potsdam, German;Pediatric Respiratory Medicine, Immunology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, German;Unit 13 Nosocomial Pathogens and Antibiotic Resistances, Robert Koch Institute, Wernigerode, German;ECDC Fellowship Programme, Public Health Microbiology Path (EUPHEM), European Centre for Disease Prevention and Control (ECDC), Solna, Swede;Unit 16 Mycotic and Parasitic Agents and Mycobacteria, Robert Koch Institute, Berlin, German;Unit 16 Mycotic and Parasitic Agents and Mycobacteria, Robert Koch Institute, Berlin, German;Unit 31 Infectious Disease Data Science Unit, Robert Koch Institute, Berlin, German;Unit MF1 Bioinformatics, Robert Koch Institute, Berlin, German;Unit NG 1 Microbial Genomics, Robert Koch Institute, Berlin, German;

关键词: Mycobacterium abscessus;    Mycobacteroides abscessus;    nontuberculous mycobacteria;    lung infection;    cystic fibrosis;    genomics;    population structure;    gene mutations;    evolution;    transmission;   

DOI  :  10.1080/21505594.2021.1959808

来源: Taylor & Francis

【 摘 要 】

Mycobacterium (M.) abscessus infections in Cystic Fibrosis (CF) patients cause a deterioration of lung function. Treatment of these multidrug-resistant pathogens is associated with severe side-effects, while frequently unsuccessful. Insight on M. abscessus genomic evolvement during chronic lung infection would be beneficial for improving treatment strategies. A longitudinal study enrolling 42 CF patients was performed at a CF center in Berlin, Germany, to elaborate phylogeny and genomic diversification of in-patient M. abscessus. Eleven of the 42 CF patients were infected with M. abscessus. Five of these 11 patients were infected with global human-transmissible M. abscessus cluster strains. Phylogenetic analysis of 88 genomes from isolates of the 11 patients excluded occurrence of M. abscessus transmission among members of the study group. Genome sequencing and variant analysis of 30 isolates from 11 serial respiratory samples collected over 4.5 years from a chronically infected patient demonstrated accumulation of gene mutations. In total, 53 genes exhibiting non-synonymous variations were identified. Enrichment analysis emphasized genes involved in synthesis of glycopeptidolipids, genes from the embABC (arabinosyltransferase) operon, betA (glucose-methanol-choline oxidoreductase) and choD (cholesterol oxidase). Genetic diversity evolved in a variety of virulence- and resistance-associated genes. The strategy of M. abscessus populations in chronic lung infection is not clonal expansion of dominant variants, but to sustain simultaneously a wide range of genetic variants facilitating adaptation of the population to changing living conditions in the lung. Genomic diversification during chronic infection requires increased attention when new control strategies against M. abscessus infections are explored.

【 授权许可】

CC BY