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Whole Genome Sequencing of Nontuberculous Mycobacterium (NTM) Isolates from Sputum Specimens of Co-Habiting Patients with NTM Pulmonary Disease and NTM Isolates from Their Environment
Jae-Joon Yim
Seoul National University College of Medicine
Corresponding Author
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This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Genomics.
Background: Nontuberculous mycobacterium (NTM) species are ubiquitous microorganisms. NTM pulmonary disease (NTM-PD) is thought to be caused not by human-to-human transmission but by independent environmental acquisition. However, recent studies using next-generation sequencing (NGS) have reported trans-continental spread of Mycobacterium abscessus among patients with cystic fibrosis.
Results: We investigated NTM genomes through NGS to examine transmission patterns in three pairs of co-habiting patients with NTM-PD who were suspected of patient-to-patient transmission. Three pairs of patients with NTM-PD co-habiting for at least 15 years were enrolled: a mother and a daughter with M. avium-PD, a couple with M. intracellulare-PD, and a second couple, one of whom was infected with M. intracellulare and the other of whom was infected with M. abscessus. Whole genome sequencing was performed using patients’ NTM isolates as well as environmental specimens. Genetic distances were estimated based on single nucleotide polymorphisms (SNPs). By comparison with the genetic distances among 78 publicly available NTM genomes, NTM isolates derived from the two pairs of patients infected with the same NTM species were not closely related to each other. In phylogenetic analysis, the NTM isolates from patients with M. avium-PD clustered with isolates from different environmental sources.
Conclusions: In conclusion, considering the genetic distances between NTM strains, the likelihood of patient-to-patient transmission in pairs of co-habiting NTM-PD patients without overt immune deficiency is minimal.
Keywords
Non-tuberculosis mycobacterium, whole genome sequencing, transmission, non-tuberculous mycobacterial pulmonary disease, phylogenomics
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Received 24 Mar, 2020
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On 22 Mar, 2020
Reviewers invited
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Reviewer #1 agreed
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Editor invited
On 21 Mar, 2020
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Review #3 received
Received 24 Dec, 2019
Editorial decision: Major revision
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Review #1 received
Received 15 Dec, 2019
Reviewer #3 agreed
On 04 Dec, 2019
Review #2 received
Received 02 Dec, 2019
Reviewer #2 agreed
On 27 Nov, 2019
Reviewers invited
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Reviewer #1 agreed
On 26 Nov, 2019
Editor invited
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This preprint is under consideration at BMC Genomics. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Whole Genome Sequencing of Nontuberculous Mycobacterium (NTM) Isolates from Sputum Specimens of Co-Habiting Patients with NTM Pulmonary Disease and NTM Isolates from Their Environment
Jae-Joon Yim
Seoul National University College of Medicine
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Published
On 23 Apr, 2020
No community comments so far
Editorial decision: Accept
On 15 Apr, 2020
Editor assigned
On 14 Apr, 2020
Submission checks complete
On 13 Apr, 2020
Editor invited
On 13 Apr, 2020
Version 3
Posted 14 Apr, 2020
No comments provided
Editorial decision: Minor revision
On 08 Apr, 2020
Editor assigned
On 07 Apr, 2020
Submission checks complete
On 06 Apr, 2020
Editor invited
On 06 Apr, 2020
No comments provided
Review #1 received
Received 02 Apr, 2020
Editorial decision: Minor revision
On 02 Apr, 2020
Reviewer #3 agreed
On 29 Mar, 2020
Review #3 received
Received 29 Mar, 2020
Review #2 received
Received 24 Mar, 2020
Reviewer #2 agreed
On 23 Mar, 2020
Editor assigned
On 22 Mar, 2020
Reviewers invited
Invitations sent on 22 Mar, 2020
Reviewer #1 agreed
On 22 Mar, 2020
Submission checks complete
On 21 Mar, 2020
Editor invited
On 21 Mar, 2020
No comments provided
Review #3 received
Received 24 Dec, 2019
Editorial decision: Major revision
On 24 Dec, 2019
Review #1 received
Received 15 Dec, 2019
Reviewer #3 agreed
On 04 Dec, 2019
Review #2 received
Received 02 Dec, 2019
Reviewer #2 agreed
On 27 Nov, 2019
Reviewers invited
Invitations sent on 26 Nov, 2019
Reviewer #1 agreed
On 26 Nov, 2019
Editor invited
On 21 Nov, 2019
Editor assigned
On 20 Nov, 2019
First submitted
On 19 Nov, 2019
Submission checks complete
On 19 Nov, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Genomics.
Background: Nontuberculous mycobacterium (NTM) species are ubiquitous microorganisms. NTM pulmonary disease (NTM-PD) is thought to be caused not by human-to-human transmission but by independent environmental acquisition. However, recent studies using next-generation sequencing (NGS) have reported trans-continental spread of Mycobacterium abscessus among patients with cystic fibrosis.
Results: We investigated NTM genomes through NGS to examine transmission patterns in three pairs of co-habiting patients with NTM-PD who were suspected of patient-to-patient transmission. Three pairs of patients with NTM-PD co-habiting for at least 15 years were enrolled: a mother and a daughter with M. avium-PD, a couple with M. intracellulare-PD, and a second couple, one of whom was infected with M. intracellulare and the other of whom was infected with M. abscessus. Whole genome sequencing was performed using patients’ NTM isolates as well as environmental specimens. Genetic distances were estimated based on single nucleotide polymorphisms (SNPs). By comparison with the genetic distances among 78 publicly available NTM genomes, NTM isolates derived from the two pairs of patients infected with the same NTM species were not closely related to each other. In phylogenetic analysis, the NTM isolates from patients with M. avium-PD clustered with isolates from different environmental sources.
Conclusions: In conclusion, considering the genetic distances between NTM strains, the likelihood of patient-to-patient transmission in pairs of co-habiting NTM-PD patients without overt immune deficiency is minimal.
Figure 1
Figure 2