Evolution of Mycobacterium abscessus in the human lung: Cumulative mutations and genomic rearrangement of porin genes in patient isolates
ABSTRACTBackground Mycobacterium abscessus subspecies massiliense (M. massiliense) is increasingly recognized as an emerging bacterial pathogen, particularly in cystic fibrosis (CF) patients and CF centres’ respiratory outbreaks. We characterized genomic and phenotypic changes in 15 serial isolates...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2023-12-01
|
| Series: | Virulence |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/21505594.2023.2215602 |
| _version_ | 1797367177209184256 |
|---|---|
| author | Shamira J. Shallom Hervé Tettelin Prabha Chandrasekaran In Kwon Park Sonia Agrawal Kriti Arora Lisa Sadzewicz Aaron M. Milstone Moira L. Aitken Barbara A. Brown-Elliott Richard J. Wallace Elizabeth P. Sampaio Michael Niederweis Kenneth N. Olivier Steven M. Holland Adrian M. Zelazny |
| author_facet | Shamira J. Shallom Hervé Tettelin Prabha Chandrasekaran In Kwon Park Sonia Agrawal Kriti Arora Lisa Sadzewicz Aaron M. Milstone Moira L. Aitken Barbara A. Brown-Elliott Richard J. Wallace Elizabeth P. Sampaio Michael Niederweis Kenneth N. Olivier Steven M. Holland Adrian M. Zelazny |
| author_sort | Shamira J. Shallom |
| collection | DOAJ |
| description | ABSTRACTBackground Mycobacterium abscessus subspecies massiliense (M. massiliense) is increasingly recognized as an emerging bacterial pathogen, particularly in cystic fibrosis (CF) patients and CF centres’ respiratory outbreaks. We characterized genomic and phenotypic changes in 15 serial isolates from two CF patients (1S and 2B) with chronic pulmonary M. massiliense infection leading to death, as well as four isolates from a CF centre outbreak in which patient 2B was the index case.Results Comparative genomic analysis revealed the mutations affecting growth rate, metabolism, transport, lipids (loss of glycopeptidolipids), antibiotic susceptibility (macrolides and aminoglycosides resistance), and virulence factors. Mutations in 23S rRNA, mmpL4, porin locus and tetR genes occurred in isolates from both CF patients. Interestingly, we identified two different spontaneous mutation events at the mycobacterial porin locus: a fusion of two tandem porin paralogs in patient 1S and a partial deletion of the first porin paralog in patient 2B. These genomic changes correlated with reduced porin protein expression, diminished 14C-glucose uptake, slower bacterial growth rates, and enhanced TNF-α induction in mycobacteria-infected THP-1 human cells. Porin gene complementation of porin mutants partly restored 14C-glucose uptake, growth rate and TNF-α levels to those of intact porin strains.Conclusions We hypothesize that specific mutations accumulated and maintained over time in M. massiliense, including mutations shared among transmissible strains, collectively lead to more virulent, host adapted lineages in CF patients and other susceptible hosts. |
| first_indexed | 2024-03-08T17:13:34Z |
| format | Article |
| id | doaj.art-1d3e83e79bc44125bc0ecce45076b372 |
| institution | Directory Open Access Journal |
| issn | 2150-5594 2150-5608 |
| language | English |
| last_indexed | 2024-03-08T17:13:34Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Virulence |
| spelling | doaj.art-1d3e83e79bc44125bc0ecce45076b3722024-01-03T17:26:57ZengTaylor & Francis GroupVirulence2150-55942150-56082023-12-0114110.1080/21505594.2023.2215602Evolution of Mycobacterium abscessus in the human lung: Cumulative mutations and genomic rearrangement of porin genes in patient isolatesShamira J. Shallom0Hervé Tettelin1Prabha Chandrasekaran2In Kwon Park3Sonia Agrawal4Kriti Arora5Lisa Sadzewicz6Aaron M. Milstone7Moira L. Aitken8Barbara A. Brown-Elliott9Richard J. Wallace10Elizabeth P. Sampaio11Michael Niederweis12Kenneth N. Olivier13Steven M. Holland14Adrian M. Zelazny15Microbiology Service, Department of Laboratory Medicine (DLM), Clinical Center, NIH, Bethesda, MD, USAInstitute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USALaboratory of Clinical Infectious Diseases (LCID), National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, USALaboratory of Clinical Infectious Diseases (LCID), National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, USAInstitute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USALaboratory of Clinical Infectious Diseases (LCID), National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, USAInstitute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USAPediatric Infectious Diseases, Johns Hopkins University, Baltimore, MD, USADivision of Pulmonary and Critical Care Medicine, University of Washington Medical Center, Seattle, WA, USAMycobacteria/Nocardia Laboratory, University of Texas Health Science Center, Tyler, TX, USAMycobacteria/Nocardia Laboratory, University of Texas Health Science Center, Tyler, TX, USALaboratory of Clinical Infectious Diseases (LCID), National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, USADepartment of Microbiology, University of Alabama, Birmingham, EnglandLaboratory of Chronic Airway Infection, Pulmonary Branch, National Heart Lung and Blood Institute (NHLBI), NIH, Bethesda, MD, USALaboratory of Clinical Infectious Diseases (LCID), National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, USAMicrobiology Service, Department of Laboratory Medicine (DLM), Clinical Center, NIH, Bethesda, MD, USAABSTRACTBackground Mycobacterium abscessus subspecies massiliense (M. massiliense) is increasingly recognized as an emerging bacterial pathogen, particularly in cystic fibrosis (CF) patients and CF centres’ respiratory outbreaks. We characterized genomic and phenotypic changes in 15 serial isolates from two CF patients (1S and 2B) with chronic pulmonary M. massiliense infection leading to death, as well as four isolates from a CF centre outbreak in which patient 2B was the index case.Results Comparative genomic analysis revealed the mutations affecting growth rate, metabolism, transport, lipids (loss of glycopeptidolipids), antibiotic susceptibility (macrolides and aminoglycosides resistance), and virulence factors. Mutations in 23S rRNA, mmpL4, porin locus and tetR genes occurred in isolates from both CF patients. Interestingly, we identified two different spontaneous mutation events at the mycobacterial porin locus: a fusion of two tandem porin paralogs in patient 1S and a partial deletion of the first porin paralog in patient 2B. These genomic changes correlated with reduced porin protein expression, diminished 14C-glucose uptake, slower bacterial growth rates, and enhanced TNF-α induction in mycobacteria-infected THP-1 human cells. Porin gene complementation of porin mutants partly restored 14C-glucose uptake, growth rate and TNF-α levels to those of intact porin strains.Conclusions We hypothesize that specific mutations accumulated and maintained over time in M. massiliense, including mutations shared among transmissible strains, collectively lead to more virulent, host adapted lineages in CF patients and other susceptible hosts.https://www.tandfonline.com/doi/10.1080/21505594.2023.2215602Mycobacterium massilienseMycobacterium abscessuscystic fibrosisPorinwhole genome sequencingimmune response |
| spellingShingle | Shamira J. Shallom Hervé Tettelin Prabha Chandrasekaran In Kwon Park Sonia Agrawal Kriti Arora Lisa Sadzewicz Aaron M. Milstone Moira L. Aitken Barbara A. Brown-Elliott Richard J. Wallace Elizabeth P. Sampaio Michael Niederweis Kenneth N. Olivier Steven M. Holland Adrian M. Zelazny Evolution of Mycobacterium abscessus in the human lung: Cumulative mutations and genomic rearrangement of porin genes in patient isolates Virulence Mycobacterium massiliense Mycobacterium abscessus cystic fibrosis Porin whole genome sequencing immune response |
| title | Evolution of Mycobacterium abscessus in the human lung: Cumulative mutations and genomic rearrangement of porin genes in patient isolates |
| title_full | Evolution of Mycobacterium abscessus in the human lung: Cumulative mutations and genomic rearrangement of porin genes in patient isolates |
| title_fullStr | Evolution of Mycobacterium abscessus in the human lung: Cumulative mutations and genomic rearrangement of porin genes in patient isolates |
| title_full_unstemmed | Evolution of Mycobacterium abscessus in the human lung: Cumulative mutations and genomic rearrangement of porin genes in patient isolates |
| title_short | Evolution of Mycobacterium abscessus in the human lung: Cumulative mutations and genomic rearrangement of porin genes in patient isolates |
| title_sort | evolution of mycobacterium abscessus in the human lung cumulative mutations and genomic rearrangement of porin genes in patient isolates |
| topic | Mycobacterium massiliense Mycobacterium abscessus cystic fibrosis Porin whole genome sequencing immune response |
| url | https://www.tandfonline.com/doi/10.1080/21505594.2023.2215602 |
| work_keys_str_mv | AT shamirajshallom evolutionofmycobacteriumabscessusinthehumanlungcumulativemutationsandgenomicrearrangementofporingenesinpatientisolates AT hervetettelin evolutionofmycobacteriumabscessusinthehumanlungcumulativemutationsandgenomicrearrangementofporingenesinpatientisolates AT prabhachandrasekaran evolutionofmycobacteriumabscessusinthehumanlungcumulativemutationsandgenomicrearrangementofporingenesinpatientisolates AT inkwonpark evolutionofmycobacteriumabscessusinthehumanlungcumulativemutationsandgenomicrearrangementofporingenesinpatientisolates AT soniaagrawal evolutionofmycobacteriumabscessusinthehumanlungcumulativemutationsandgenomicrearrangementofporingenesinpatientisolates AT kritiarora evolutionofmycobacteriumabscessusinthehumanlungcumulativemutationsandgenomicrearrangementofporingenesinpatientisolates AT lisasadzewicz evolutionofmycobacteriumabscessusinthehumanlungcumulativemutationsandgenomicrearrangementofporingenesinpatientisolates AT aaronmmilstone evolutionofmycobacteriumabscessusinthehumanlungcumulativemutationsandgenomicrearrangementofporingenesinpatientisolates AT moiralaitken evolutionofmycobacteriumabscessusinthehumanlungcumulativemutationsandgenomicrearrangementofporingenesinpatientisolates AT barbaraabrownelliott evolutionofmycobacteriumabscessusinthehumanlungcumulativemutationsandgenomicrearrangementofporingenesinpatientisolates AT richardjwallace evolutionofmycobacteriumabscessusinthehumanlungcumulativemutationsandgenomicrearrangementofporingenesinpatientisolates AT elizabethpsampaio evolutionofmycobacteriumabscessusinthehumanlungcumulativemutationsandgenomicrearrangementofporingenesinpatientisolates AT michaelniederweis evolutionofmycobacteriumabscessusinthehumanlungcumulativemutationsandgenomicrearrangementofporingenesinpatientisolates AT kennethnolivier evolutionofmycobacteriumabscessusinthehumanlungcumulativemutationsandgenomicrearrangementofporingenesinpatientisolates AT stevenmholland evolutionofmycobacteriumabscessusinthehumanlungcumulativemutationsandgenomicrearrangementofporingenesinpatientisolates AT adrianmzelazny evolutionofmycobacteriumabscessusinthehumanlungcumulativemutationsandgenomicrearrangementofporingenesinpatientisolates |