Antimicrobial Susceptibility and Phylogenetic Relations in a German Cohort Infected with Mycobacterium abscessus

Wetzstein, Nils; Kohl, Thomas A.; Schultze, Tilman; Andres, Sönke; Bellinghausen, Carla; Hügel, Christian; Kempf, Volkhard A. J.; Lehn, Annette; Hogardt, Michael; Vehreschild, Maria J. G. T.; Wolf, Timo; Niemann, Stefan; Maurer, Florian P.; Wichelhaus, Thomas A.

doi:10.1128/jcm.01813-20

Cited by 23 publications

(32 citation statements)

References 30 publications

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“…Comparison of accessory genomes for discrimination of closely related MABS isolates was also proposed by Davidson [ 54 ] and Doyle and colleagues [ 55 ]. There is meanwhile a greater number of publications (e.g [ 55 , 56 , 57 ]) reporting the presence of global cluster strains in patient cohorts without epidemiologic evidence for transmission among patients. The absence of patient-to-patient transmission endorses infection control measures in the CF center in Berlin which involve among others spatial and/or temporal separation of patients with NTM in respiratory tract and wearing a face mask during the entire clinical stay [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

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Genetic diversification of persistent Mycobacterium abscessus within cystic fibrosis patients

et al. 2021

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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 cho D (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.

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Section: Discussionmentioning

confidence: 99%

“…ChoD, a cholesterol oxidase, is needed in M. tuberculosis survival in macrophages [49]. A mutant deficient in the gamma-glutamyl-transpeptidase (GgtB) from M. tuberculosis, which is homologous to MAB_2788, was shown to be resistant to the toxic effects of Glutathione/ S-nitrosoglutathione and therefore better survived in macrophages [47].…”

Section: Discussionmentioning

confidence: 99%

Genetic diversification of persistent Mycobacterium abscessus within cystic fibrosis patients

et al. 2021

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“…Other studies (e.g. [52, 53]) had also reported the presence of global cluster strains in patient cohorts without evidence for transmission among patients. The absence of patient-to-patient transmission endorses infection control measures in the CF center in Berlin which involve among others spatial and/or temporal separation of patients with NTM in respiratory tract and a face mask wearing during the entire clinical stay [54].…”

Section: Discussionmentioning

confidence: 99%

Genetic diversification of persistentMycobacterium abscessuswithin Cystic Fibrosis patients

Lewin

Kamal

Semmler

et al. 2021

Preprint

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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. Global human-transmissible M. abscessus cluster strains were isolated from five of these 11 patients. 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 four 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.

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“…In particular, we calculated pairwise allele and SNP distances between 76 isolates (Additional file 1: Table S6) from three previously defined extra-pulmonary outbreaks and 12 putative intra-hospital transmission clusters: (i) an outbreak of post-surgical wound infections in Brazil 42 , (ii) an outbreak of post-tattooing skin infections in Quebeq 21 , (iii) an outbreak of otitis media in paediatric patients in Quebeq 21 , and (iv) isolates from CF patients attending clinics in Papworth, Seattle, Milan, Florence or Frankfurt. For some of these CF patients, indirect cross-infection within the hospital was proposed, while for the others, epidemiological investigations did not support this transmission mode 12,15,43,44 (Additional file 1: Table S6).…”

Section: Transmission and Outbreak Analysismentioning

confidence: 99%

“…. C. Pairwise distances between related isolates from cystic fibrosis (CF) patients for which epi data did not support nosocomial transmission 15,43 . For B and C, clusters were previously defined with a threshold of 30 SNPs.…”

Section: Transmission and Outbreak Analysismentioning

confidence: 99%

Delineating Mycobacterium abscessus population structure and transmission employing high-resolution core genome multilocus sequence typing

Diricks

Merker

Wetzstein

et al. 2022

Preprint

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Mycobacterium abscessus (Mab) is an emerging multidrug-resistant nontuberculous mycobacterium that causes a wide spectrum of infections and has caused several local outbreaks worldwide. To facilitate standardized prospective molecular surveillance, we established a novel core genome multilocus sequence typing (cgMLST) scheme. Over 2000 isolates of Mab, covering all subspecies and main dominant circulating clones as well as extra-pulmonary outbreak strains and sequential isolates of chronically infected cystic fibrosis patients, were used to validate the scheme and set genetic distance thresholds to delineate transmission events and global population structure. Most global clonal complexes previously classified using cgSNP were confirmed by our cgMLST approach, and also correlated well with traditional 7-loci MLST sequence types. 99% of pairwise comparisons between epidemiologically linked isolates were below 25 alleles and 90% below 10 alleles. These thresholds can be used for initial cluster analysis and to guide further epidemiological investigations. Overall, the scheme will help to unravel the apparent global spread of certain clonal complexes and as yet undiscovered transmission routes.

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Antimicrobial Susceptibility and Phylogenetic Relations in a German Cohort Infected with Mycobacterium abscessus

Cited by 23 publications

References 30 publications

Genetic diversification of persistent Mycobacterium abscessus within cystic fibrosis patients

Genetic diversification of persistent Mycobacterium abscessus within cystic fibrosis patients

Genetic diversification of persistentMycobacterium abscessuswithin Cystic Fibrosis patients

Delineating Mycobacterium abscessus population structure and transmission employing high-resolution core genome multilocus sequence typing

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