Beijing sublineages of Mycobacterium tuberculosis differ in pathogenicity in the guinea pig
The Beijing family of Mycobacterium tuberculosis strains is part of lineage 2 (also known as the East Asian lineage). In clinical studies, we have observed that isolates from the sublineage RD207 of lineage 2 were more readily transmitted among humans. To investigate the basis for this difference, w...
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| Veröffentlicht in: | Clinical and vaccine immunology Jg. 19; H. 8; S. 1227 |
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| Abstract | The Beijing family of Mycobacterium tuberculosis strains is part of lineage 2 (also known as the East Asian lineage). In clinical studies, we have observed that isolates from the sublineage RD207 of lineage 2 were more readily transmitted among humans. To investigate the basis for this difference, we tested representative strains with the characteristic Beijing spoligotype from four of the five sublineages of lineage 2 in the guinea pig model and subjected these strains to comparative whole-genome sequencing. The results of these studies showed that all of the clinical strains were capable of growing and causing lung pathology in guinea pigs after low-dose aerosol exposure. Differences between the abilities of the four sublineages to grow in the lungs of these animals were not overt, but members of RD207 were significantly more pathogenic, resulting in severe lung damage. The RD207 strains also induced much higher levels of markers associated with regulatory T cells and showed a significant loss of activated T cells in the lungs over the course of the infections. Whole-genome sequencing of the strains revealed mutations specific for RD207 which may explain this difference. Based on these data, we hypothesize that the sublineages of M. tuberculosis are associated with distinct pathological and clinical phenotypes and that these differences influence the transmissibility of particular M. tuberculosis strains in human populations. |
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| AbstractList | The Beijing family of Mycobacterium tuberculosis strains is part of lineage 2 (also known as the East Asian lineage). In clinical studies, we have observed that isolates from the sublineage RD207 of lineage 2 were more readily transmitted among humans. To investigate the basis for this difference, we tested representative strains with the characteristic Beijing spoligotype from four of the five sublineages of lineage 2 in the guinea pig model and subjected these strains to comparative whole-genome sequencing. The results of these studies showed that all of the clinical strains were capable of growing and causing lung pathology in guinea pigs after low-dose aerosol exposure. Differences between the abilities of the four sublineages to grow in the lungs of these animals were not overt, but members of RD207 were significantly more pathogenic, resulting in severe lung damage. The RD207 strains also induced much higher levels of markers associated with regulatory T cells and showed a significant loss of activated T cells in the lungs over the course of the infections. Whole-genome sequencing of the strains revealed mutations specific for RD207 which may explain this difference. Based on these data, we hypothesize that the sublineages of M. tuberculosis are associated with distinct pathological and clinical phenotypes and that these differences influence the transmissibility of particular M. tuberculosis strains in human populations.The Beijing family of Mycobacterium tuberculosis strains is part of lineage 2 (also known as the East Asian lineage). In clinical studies, we have observed that isolates from the sublineage RD207 of lineage 2 were more readily transmitted among humans. To investigate the basis for this difference, we tested representative strains with the characteristic Beijing spoligotype from four of the five sublineages of lineage 2 in the guinea pig model and subjected these strains to comparative whole-genome sequencing. The results of these studies showed that all of the clinical strains were capable of growing and causing lung pathology in guinea pigs after low-dose aerosol exposure. Differences between the abilities of the four sublineages to grow in the lungs of these animals were not overt, but members of RD207 were significantly more pathogenic, resulting in severe lung damage. The RD207 strains also induced much higher levels of markers associated with regulatory T cells and showed a significant loss of activated T cells in the lungs over the course of the infections. Whole-genome sequencing of the strains revealed mutations specific for RD207 which may explain this difference. Based on these data, we hypothesize that the sublineages of M. tuberculosis are associated with distinct pathological and clinical phenotypes and that these differences influence the transmissibility of particular M. tuberculosis strains in human populations. The Beijing family of Mycobacterium tuberculosis strains is part of lineage 2 (also known as the East Asian lineage). In clinical studies, we have observed that isolates from the sublineage RD207 of lineage 2 were more readily transmitted among humans. To investigate the basis for this difference, we tested representative strains with the characteristic Beijing spoligotype from four of the five sublineages of lineage 2 in the guinea pig model and subjected these strains to comparative whole-genome sequencing. The results of these studies showed that all of the clinical strains were capable of growing and causing lung pathology in guinea pigs after low-dose aerosol exposure. Differences between the abilities of the four sublineages to grow in the lungs of these animals were not overt, but members of RD207 were significantly more pathogenic, resulting in severe lung damage. The RD207 strains also induced much higher levels of markers associated with regulatory T cells and showed a significant loss of activated T cells in the lungs over the course of the infections. Whole-genome sequencing of the strains revealed mutations specific for RD207 which may explain this difference. Based on these data, we hypothesize that the sublineages of M. tuberculosis are associated with distinct pathological and clinical phenotypes and that these differences influence the transmissibility of particular M. tuberculosis strains in human populations. |
| Author | Henao-Tamayo, Marcela Basaraba, Randall J Fofanov, Viacheslav Y Shanley, Crystal A Obregon-Henao, Andres Rose, Jordan Hopewell, Philip C Gagneux, Sebastien Barrozo, Joyce C Coscolla, Mireia Koshinsky, Heather Orme, Ian M Jarlsberg, Leah G Kawamura, L Masae Ordway, Diane J Ackart, David Harton, Marisabel Kato-Maeda, Midori Shang, Shaobin |
| Author_xml | – sequence: 1 givenname: Midori surname: Kato-Maeda fullname: Kato-Maeda, Midori email: midori.kato-maeda@ucsf.edu organization: Curry International Tuberculosis Center, Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, California, USA. midori.kato-maeda@ucsf.edu – sequence: 2 givenname: Crystal A surname: Shanley fullname: Shanley, Crystal A – sequence: 3 givenname: David surname: Ackart fullname: Ackart, David – sequence: 4 givenname: Leah G surname: Jarlsberg fullname: Jarlsberg, Leah G – sequence: 5 givenname: Shaobin surname: Shang fullname: Shang, Shaobin – sequence: 6 givenname: Andres surname: Obregon-Henao fullname: Obregon-Henao, Andres – sequence: 7 givenname: Marisabel surname: Harton fullname: Harton, Marisabel – sequence: 8 givenname: Randall J surname: Basaraba fullname: Basaraba, Randall J – sequence: 9 givenname: Marcela surname: Henao-Tamayo fullname: Henao-Tamayo, Marcela – sequence: 10 givenname: Joyce C surname: Barrozo fullname: Barrozo, Joyce C – sequence: 11 givenname: Jordan surname: Rose fullname: Rose, Jordan – sequence: 12 givenname: L Masae surname: Kawamura fullname: Kawamura, L Masae – sequence: 13 givenname: Mireia surname: Coscolla fullname: Coscolla, Mireia – sequence: 14 givenname: Viacheslav Y surname: Fofanov fullname: Fofanov, Viacheslav Y – sequence: 15 givenname: Heather surname: Koshinsky fullname: Koshinsky, Heather – sequence: 16 givenname: Sebastien surname: Gagneux fullname: Gagneux, Sebastien – sequence: 17 givenname: Philip C surname: Hopewell fullname: Hopewell, Philip C – sequence: 18 givenname: Diane J surname: Ordway fullname: Ordway, Diane J – sequence: 19 givenname: Ian M surname: Orme fullname: Orme, Ian M |
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| SubjectTerms | Animals Disease Models, Animal Female Genome, Bacterial Genotype Guinea Pigs Histocytochemistry Humans Lung - microbiology Lung - pathology Molecular Typing Mycobacterium tuberculosis - classification Mycobacterium tuberculosis - genetics Mycobacterium tuberculosis - isolation & purification Mycobacterium tuberculosis - pathogenicity Sequence Analysis, DNA Tuberculosis - microbiology Tuberculosis - pathology Virulence |
| Title | Beijing sublineages of Mycobacterium tuberculosis differ in pathogenicity in the guinea pig |
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