A Pilot Proteomics Analysis of Mycobacterium tuberculosis Lacking a Putative Short-Chain Dehydrogenase Rv0148

Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that survives in host cells by resisting hostile antimicrobial defenses. However, the molecules and mechanisms that contribute to Mtb's intracellular survival are not fully understood. We have previously reported that Rv0148, a putative short-chain dehydrogenase/reductase, plays a significant role in Mtb stress response and virulence in in vitro and in vivo models. To further understand the role of Rv0148 in regulating global functions of Mtb, we performed comparative pilot proteomic analysis between Δrv0148 mutant, and wild-type (WT) strains grown in axenic cultures. Mass spectrometry-based proteomics analysis identified 586 and 626 statistically significant differentially abundant proteins (SSDAP) in the WT and Δrv0148 mutant, respectively. Ontology analysis revealed that proteins involved in biological processes, including bacterial adaptation to host responses and protein homeostasis, were significantly more abundant, while peptidoglycan biosynthesis was less abundant in the mutant than the WT. Further network analysis revealed dysregulation of proteins involved in bacterial stress response, cell wall components, ribosomal and secretory proteins, suggesting impaired cell wall and translation machinery in Δrv0148. Functional categorization of differentially regulated proteins in Δrv0148 showed broad reprogramming in intermediary metabolism and stress adaptation. These findings suggest that Rv0148 may influence remodeling of cell wall components and bacterial physiology, potentially balancing Mtb survival and stress adaptation.