The lysine acetyltransferase Rv0998 coordinates transcriptional and metabolic adaptation of Mycobacterium tuberculosis to acidic pH.

Loss of the lysine acetyltransferase Rv0998 impairs Mycobacterium tuberculosis growth at acidic pH and alters its transcriptional and metabolic responses.

• Why it matters: Understanding how Mtb adapts to host-induced acid stress is crucial for developing strategies to combat tuberculosis, as the regulatory links between stress responses and metabolism are not fully known.
• What they did: Researchers deleted rv0998 in Mtb and used RNA-seq and stable isotope tracing with [U-13C6]-glucose to analyze changes in gene expression and carbon metabolism under acidic conditions, focusing on central carbon metabolites.
• The result: The rv0998 mutant showed reduced growth at acidic pH with glucose, broad transcriptional changes including in the DosR regulon and pfkB, and decreased incorporation of glucose-derived carbon into central metabolites, highlighting Rv0998’s role in coordinating acid stress adaptation and metabolism.