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In vitro Investigation of the MexAB Efflux Pump From Pseudomonas aeruginosa
Published on: February 17, 2014
Protonation Based Molecular Mechanism Behind Rv0191 Efflux Transporter Conferring Pyrazinamide Resistance in
Deepti Dhusia1, Garima Singh1, Dinesh Raj Modi1
1Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, India.
Proteins
|August 12, 2026
Summary
Multidrug-resistant TB (MDR TB) efflux pumps, like Rv0191, contribute to antibiotic resistance by exporting drugs such as pyrazinamide (PZA). Understanding these efflux mechanisms is key to developing new MDR TB treatments.
Area of Science:
- Molecular Biology
- Biochemistry
- Structural Biology
Background:
- Multidrug-resistant tuberculosis (MDR TB) is a major global health threat, driven by complex drug resistance mechanisms.
- Major Facilitator Superfamily (MFS) transporters are implicated in mediating antibiotic resistance in Mycobacterium tuberculosis (Mtb).
- The Rv0191 efflux transporter is a potential key player in MDR TB, specifically involved in pyrazinamide (PZA) efflux.
Purpose of the Study:
- To elucidate the detailed molecular mechanism of Rv0191-mediated drug efflux.
- To investigate the role of Rv0191 in pyrazinamide (PZA) resistance in Mtb.
- To explore the structural dynamics and protonation-driven efflux pathway of Rv0191.
Main Methods:
- Molecular dynamics (MD) simulations of Rv0191 in both outward-open and inward-open conformations.
- Simulations were conducted in a lipid bilayer environment for 500 ns in triplicate.
- Analysis of structural dynamics, binding interactions, and substrate translocation pathways.
Main Results:
- Rv0191 possesses a central tunnel with a distinct binding pocket for PZA.
- MD simulations revealed a protonation-driven efflux mechanism, highlighting functional differences between conformational states.
- Structural analyses indicated specific PZA-Rv0191 interactions and conformational changes facilitating PZA translocation.
Conclusions:
- Rv0191 mediates PZA efflux through a protonation-driven mechanism via a central tunnel.
- The findings suggest a plausible pathway for MFS-mediated drug resistance in Mtb.
- Rv0191 represents a potential therapeutic target for combating MDR TB.
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