Panb Over-Representation as Part of Pyrazinamide Action: A Proteomic Insight

Abstract

Background: Pyrazinamide (PZA) represents a milestone as a first-line antituberculosis drug due to its sterilizing activity against Mycobacterium tuberculosis. Materials & Methods: The protein changes induced by subinhibitory PZA exposure of M. tuberculosis in acidic pH were evaluated by a proteomic approach. Results: Among the 1059 M. tuberculosis proteins identified, the specific acidification in the culture medium induced the over-representation of MurF (Rv2157c), and its under-representation was induced by 12 h of PZA exposure. PanB (Rv2225) was over-represented at 24 h of PZA exposure. Conclusion: The authors highlight the over-representation of PanB in M. tuberculosis correlates of PZA action in acidic pH, reinforcing the role of the pantothenate pathway as a bacillus drug target to be explored.

Keywords::

• drug targets
• Mycobacterium tuberculosis
• proteomics
• pyrazinamide
• tuberculosis

Author contributions

RF Cardoso, PAZ Campanerut-Sá and LD Ghiraldi-Lopes worked on the design/concept of this work, drafting and final approval of the version to be published; ILE Barros, JE Meneguello, GS Arita, JV de Oliveira Silva and EJ Pilau implemented this study and data analysis; KRC Ferracioli, RB de Lima Scodro and VLD Siqueira worked on the critical revision of the manuscript. All authors have read and agreed to the final version of the manuscript.

Data are available via ProteomeXchange with identifier PXD025831.

Financial & competing interests disclosure

The authors thank the Brazilian Coordination for the Improvement of Higher Education Personnel (CAPES) and the Laboratory for Teaching and Research in Clinical Analysis (LEPAC-UEM) for academically supporting this study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The authors thank the Brazilian Coordination for the Improvement of Higher Education Personnel (CAPES) and the Laboratory for Teaching and Research in Clinical Analysis (LEPAC-UEM) for academically supporting this study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.