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Research article
Genome sequencing of Mycobacterium pinnipedii strains: genetic characterization and evidence of superinfection in a South American sea lion (Otaria flavescens)
Ana M. S. Guimarães
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8261-5863
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View the published version at BMC Genomics.
Background: Mycobacterium pinnipedii , a member of the Mycobacterium tuberculosis Complex (MTBC), is capable of infecting several host species, including humans. Recently, ancient DNA from this organism was recovered from pre-Columbian mummies of Peru, sparking debate over the origin and frequency of tuberculosis in the Americas prior to European colonization.
Results: We present the first comparative genomic study of this bacterial species, starting from the genome sequencing of two M. pinnipedii isolates (MP1 and MP2) obtained from different organs of a stranded South American sea lion. Our results indicate that MP1 and MP2 differ by 113 SNPs (single nucleotide polymorphisms) and 46 indels, constituting the first report of a mixed-strain infection in a sea lion. SNP annotation analyses indicate that genes of the VapBC family, a toxin-antitoxin system, and genes related to cell wall remodeling are under evolutionary pressure for protein sequence change in these strains. OrthoMCL analysis with seven modern isolates of M. pinnipedii shows that these strains have highly similar proteomes. Gene variations were only marginally associated with hypothetical proteins and PE/PPE (proline-glutamate and proline-proline-glutamate, respectively) gene families. We also detected large deletions in ancient and modern M. pinnipedii strains, including a few occurring only in modern strains, indicating a process of genome reduction occurring over the past one thousand years. Our phylogenomic analyses suggest the existence of two modern clusters of M. pinnipedii associated with geographic location, and possibly host species, and one basal node associated with the ancient M. pinnipedii strains. Previously described MiD3 and MiD4 deletions may have occurred independently, twice, over the evolutionary course of the MTBC.
Conclusion: The presence of superinfection (i.e. mixed-strain infection) in this sea lion suggests that M. pinnipedii is highly endemic in this population. Mycobacterium pinnipedii proteomes of the studied isolates showed a high degree of conservation, despite being under genomic decay when compared to M. tuberculosis. This finding indicates that further genomes need to be sequenced and analyzed to increase the chances of finding variably present genes among strains or that M. pinnipedii genome remodeling occurred prior to bacterial speciation.
Keywords
Mycobacterium pinnipedii, genome, superinfection, comparative genomics, Mycobacterium tuberculosis Complex.
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Editorial decision: Minor revision
On 12 Dec, 2019
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On 09 Dec, 2019
Editor invited
On 09 Dec, 2019
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Editorial decision: Minor revision
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Received 27 Nov, 2019
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On 13 Nov, 2019
Reviewers invited
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On 12 Nov, 2019
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Received 12 Nov, 2019
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On 11 Nov, 2019
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On 10 Nov, 2019
Editor invited
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Editorial decision: Major revision
On 08 Oct, 2019
Review #2 received
Received 29 Sep, 2019
Reviewer #2 agreed
On 14 Sep, 2019
Review #1 received
Received 04 Jul, 2019
Reviewer #1 agreed
On 22 Jun, 2019
Reviewers invited
Invitations sent on 19 Jun, 2019
Editor assigned
On 29 May, 2019
Submission checks complete
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On 22 May, 2019
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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
Genome sequencing of Mycobacterium pinnipedii strains: genetic characterization and evidence of superinfection in a South American sea lion (Otaria flavescens)
Ana M. S. Guimarães
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8261-5863
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
Version 4
Posted 20 Dec, 2019
Published
On 30 Dec, 2019
No community comments so far
Submission checks complete
On 18 Dec, 2019
Editorial decision: Accept
On 16 Dec, 2019
No comments provided
Editorial decision: Minor revision
On 12 Dec, 2019
Editor assigned
On 10 Dec, 2019
Submission checks complete
On 09 Dec, 2019
Editor invited
On 09 Dec, 2019
No comments provided
Editorial decision: Minor revision
On 30 Nov, 2019
Review #2 received
Received 27 Nov, 2019
Reviewer #2 agreed
On 13 Nov, 2019
Reviewers invited
Invitations sent on 12 Nov, 2019
Reviewer #1 agreed
On 12 Nov, 2019
Review #1 received
Received 12 Nov, 2019
Editor assigned
On 11 Nov, 2019
Submission checks complete
On 10 Nov, 2019
Editor invited
On 10 Nov, 2019
No comments provided
Editorial decision: Major revision
On 08 Oct, 2019
Review #2 received
Received 29 Sep, 2019
Reviewer #2 agreed
On 14 Sep, 2019
Review #1 received
Received 04 Jul, 2019
Reviewer #1 agreed
On 22 Jun, 2019
Reviewers invited
Invitations sent on 19 Jun, 2019
Editor assigned
On 29 May, 2019
Submission checks complete
On 22 May, 2019
Editor invited
On 22 May, 2019
First submitted
On 11 May, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Epigenetics & Genomics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Genomics.
Background: Mycobacterium pinnipedii , a member of the Mycobacterium tuberculosis Complex (MTBC), is capable of infecting several host species, including humans. Recently, ancient DNA from this organism was recovered from pre-Columbian mummies of Peru, sparking debate over the origin and frequency of tuberculosis in the Americas prior to European colonization.
Results: We present the first comparative genomic study of this bacterial species, starting from the genome sequencing of two M. pinnipedii isolates (MP1 and MP2) obtained from different organs of a stranded South American sea lion. Our results indicate that MP1 and MP2 differ by 113 SNPs (single nucleotide polymorphisms) and 46 indels, constituting the first report of a mixed-strain infection in a sea lion. SNP annotation analyses indicate that genes of the VapBC family, a toxin-antitoxin system, and genes related to cell wall remodeling are under evolutionary pressure for protein sequence change in these strains. OrthoMCL analysis with seven modern isolates of M. pinnipedii shows that these strains have highly similar proteomes. Gene variations were only marginally associated with hypothetical proteins and PE/PPE (proline-glutamate and proline-proline-glutamate, respectively) gene families. We also detected large deletions in ancient and modern M. pinnipedii strains, including a few occurring only in modern strains, indicating a process of genome reduction occurring over the past one thousand years. Our phylogenomic analyses suggest the existence of two modern clusters of M. pinnipedii associated with geographic location, and possibly host species, and one basal node associated with the ancient M. pinnipedii strains. Previously described MiD3 and MiD4 deletions may have occurred independently, twice, over the evolutionary course of the MTBC.
Conclusion: The presence of superinfection (i.e. mixed-strain infection) in this sea lion suggests that M. pinnipedii is highly endemic in this population. Mycobacterium pinnipedii proteomes of the studied isolates showed a high degree of conservation, despite being under genomic decay when compared to M. tuberculosis. This finding indicates that further genomes need to be sequenced and analyzed to increase the chances of finding variably present genes among strains or that M. pinnipedii genome remodeling occurred prior to bacterial speciation.
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