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OpuC--an ABC transporter that is associated with Staphylococcus aureus pathogenesis
Madanahally D Kiran1, Donna E Akiyoshi, Andrea Giacometti
1Department of Biological Sciences, Tufts University, Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
The International Journal of Artificial Organs
|October 27, 2009
Summary
The novel antibiotic RIP targets staphylococci by inhibiting TRAP phosphorylation and agr expression. Researchers found OpuC, a transporter, is crucial for TRAP function and Staphylococcus aureus pathogenesis.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Staphylococcus aureus virulence is regulated by the accessory gene regulator (agr) quorum sensing system.
- The function of the highly conserved, membrane-associated TRAP protein in staphylococci, involved in DNA protection, is not well understood.
- The novel antibiotic RIP targets staphylococci by downregulating TRAP histidine phosphorylation and accessory gene regulator (agr) expression.
Purpose of the Study:
- To identify proteins that interact with TRAP.
- To investigate the role of TRAP-interacting proteins in Staphylococcus aureus pathogenesis.
Main Methods:
- Bacterial two-hybrid system for protein-protein interaction studies.
- Construction and characterization of a Staphylococcus aureus OpuC- mutant strain.
- Assessment of salt tolerance, choline uptake, TRAP phosphorylation, agr activity, and biofilm formation.
Main Results:
- OpuCA, an ATP binding-cytoplasmic (ABC) domain of the OpuC transporter, was identified as a TRAP-binding protein.
- OpuC- mutant strains exhibited reduced salt tolerance and defective choline uptake.
- OpuC- mutants displayed decreased pathogenicity, reduced TRAP phosphorylation and agr activity, impaired response to RNAIII activating protein (RAP), and defective biofilm formation in vitro and in vivo.
Conclusions:
- OpuC functions as a transporter and plays a significant role in Staphylococcus aureus pathogenesis.
- OpuC interacts with TRAP, influencing TRAP phosphorylation and downstream virulence pathways.
- Targeting the OpuC transporter or its interaction with TRAP may represent a novel therapeutic strategy against staphylococcal infections.
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