A multidrug ABC transporter with a taste for GTP

Area of Science:

• Biochemistry
• Molecular Biology
• Microbiology

Background:

• Cellular bioenergetics involves protein families adapted to energy supply.
• Adenosine triphosphate (ATP)-Binding Cassette (ABC) transporters are typically powered by ATP hydrolysis.
• Many medically relevant proteins utilize ATP or guanosine triphosphate (GTP) for function.

Purpose of the Study:

• To investigate the energy source utilized by the Streptococcus pneumoniae ABC transporter, PatA/PatB.
• To determine if PatA/PatB challenges the conventional understanding of ABC transporter energy supply.

Main Methods:

• Reconstitution of the PatA/PatB transporter in proteoliposomes and nanodiscs.
• Assays to measure the hydrolysis of ATP and GTP by the reconstituted transporter.
• Analysis of intracellular ATP and GTP concentrations in Streptococcus pneumoniae.

Main Results:

• The PatA/PatB transporter from Streptococcus pneumoniae preferentially utilizes GTP over ATP for drug expulsion.
• PatA/PatB exhibits higher efficiency in hydrolyzing GTP compared to ATP.
• Intracellular concentrations of ATP and GTP are comparable in S. pneumoniae, supporting GTP's physiological relevance for this transporter.

Conclusions:

• The PatA/PatB transporter represents a significant exception to the rule of ATP-dependent ABC transporters.
• GTP can serve as a primary energy source for bacterial ABC transporters, particularly in Streptococcus pneumoniae.
• This finding has implications for understanding bacterial resistance mechanisms and developing novel antimicrobial strategies.