The lysine acetyltransferase Rv0998 coordinates transcriptional and metabolic adaptation of Mycobacterium tuberculosis to acidic pH
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Mycobacterium tuberculosis (Mtb) survives host defences by adapting to host conditions, including acid stress, during infection. A critical survival strategy involves pH homeostasis, mediated by complex signalling systems that regulate metabolic reprogramming and stress responses. While the lysine acetyltransferase Rv0998 is known to support Mtb hypoxia adaptation and metabolic flexibility, its role in acid stress remains unexplored. Here, we investigated the consequences of rv0998 deletion in 7H9 with glucose as the major carbon source. RNA-seq analysis showed that loss of Rv0998 altered the transcriptional response to acidic pH, including changes in the DosR regulon and pfkB/Rv2029c. Stable isotope tracing with [U-13C6]-glucose also showed reduced fractional 13C labelling across central carbon metabolites in the rv0998 mutant, with the largest decrease at acidic pH observed in upper glycolytic and connected hexose-phosphate intermediates. Growth and glucose-labelling phenotypes of dosR and pfkB mutants provided focused examples of stress-responsive and carbon-metabolic processes associated with the broader Rv0998 response. These findings indicate that Rv0998 contributes to coordinated transcriptional and metabolic adaptation of Mtb to acidic pH and support further investigation of how stress-responsive regulatory programmes are coupled to carbon metabolism during acid adaptation.
Date Acceptance
2026-09-03
Citation
Journal of Bacteriology
ISSN
0021-9193
Publisher
American Society for Microbiology
Journal / Book Title
Journal of Bacteriology
Copyright Statement
Copyright © 2026 Journal of Bacteriology. This is the author’s accepted manuscript made available under a CC-BY licence in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy)
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Publication Status
Accepted