Variation in pre-therapy levels of selected Mycobacterium tuberculosis transcripts insputumand their relationship with 2-month culture conversion
File(s)
Author(s)
Rockwood, Neesha
Lai, Rachel PJ
Seldon, Ronnett
Young, Douglas
Wilkinson, Robert
Type
Journal Article
Abstract
Background: The abundance of transcripts arising from Mycobacterium tuberculosis (MTB) in sputum pre-chemotherapy may enhance our understanding of factors influencing treatment response. We hypothesized that differences in the prevalence of pre-existing slowly metabolizing MTB in sputum may be partially responsible for differences in the rate of sputum clearance during treatment. Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to characterize a selected limited transcription profile of MTB in sputum pre-chemotherapy and assess inter-individual variation. The difference in cycle threshold (Ct) per gene, normalized to 16S, between exponential/stationary phase culture and sputum was calculated and stratified by 2-month culture converter status. Results: HIV-1 uninfected patients with rifampicin-susceptible tuberculosis provided sputum pre-chemotherapy; 11 patients were negative for MTB culture after two months of therapy and 8 remained culture-positive. Increased icl1 and prpD and rpsN2:rpsN1 in sputum relative to culture suggested cholesterol utilization and a low-zinc environment respectively. Increased hspX and decreased atpA and nuoG relative to exponential culture suggested a slowly metabolizing subpopulation of MTB. While the the hspX hi atpA lo nuoG lo signal varied, we did not observe statistically significant enrichment of this phenotype in the non-converter population nor an association with MTB-lineage. Conclusion: Differential abundance of selected informative transcripts suggested a metabolically less-active subpopulation with a prevalence that varied between individual untreated patients.
Date Issued
2019-07-05
Date Acceptance
2019-07-01
Citation
Wellcome Open Research, 2019, 106 (4), pp.1-9
ISSN
2398-502X
Publisher
F1000Research
Start Page
1
End Page
9
Journal / Book Title
Wellcome Open Research
Volume
106
Issue
4
Copyright Statement
© 2019 Rockwood N et al. This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Identifier
https://wellcomeopenresearch.org/articles/4-106/v1
Publication Status
Published
Date Publish Online
2019-07-05