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bioRxiv · 10.1101/2020.03.09.983163

Transcriptomic characterization of tuberculous sputum reveals a host Warburg effect and microbial cholesterol catabolism

Lai, R. P.·Cortes, T.·Marais, S.·Rockwood, N.·Burke, M. L.·Garza-Garcia, A.·Horswell, S.·O'Garra, A.·Young, D. B.·Wilkinson, R. J.
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Abstract

The crucial transmission phase of tuberculosis (TB) relies on infectious sputum yet cannot easily be modeled. We applied one-step RNA-Sequencing to sputum from infectious TB patients to investigate the host and microbial environments underlying transmission of Mycobacterium tuberculosis (Mtb). In such TB sputa, compared to non-TB controls, transcriptional upregulation of inflammatory responses and a metabolic shift towards glycolysis was observed in the host. Amongst all bacterial sequences in the sputum, only less than 1.5% originated from Mtb and its abundance is associated with HIV-1 coinfection status. The transcriptome of sputum Mtb more closely resembled aerobic replication and was characterized by evidence of cholesterol utilization, zinc deprivation and reduced expression of the virulence-associated PhoP regulon. Our study provides a comprehensive analysis of the transcriptional landscape associated with infectious sputum and demonstrates the feasibility of applying advanced sequencing technology to readily accessible pathological specimens in the study of host-pathogen adaptation.

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Lai, R. P., Cortes, T., Marais, S., Rockwood, N., Burke, M. L., Garza-Garcia, A., Horswell, S., O'Garra, A., Young, D. B., Wilkinson, R. J.. 2020-03-09. Transcriptomic characterization of tuberculous sputum reveals a host Warburg effect and microbial cholesterol catabolism. https://doi.org/10.1101/2020.03.09.983163

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