OpuC--an ABC transporter that is associated with Staphylococcus aureus pathogenesis.
RIP is a novel antibiotic against staphylococci. It acts at least in part by competing with RNAIII activating protein (RAP) by downregulating TRAP histidine phosphorylation, and by downregulating the expression of the acessory gene regulator (agr). While much is known about the function of the agr as a quorum sensing system that regulates virulence, not much is known about TRAP. TRAP is a 167-kDa protein that is highly conserved among staphylococci and is involved in DNA protection from stress. TRAP is membrane-associated but does not have a transmembrane domain, and thus it may be bound to the membrane through other proteins. To search for these proteins, protein-protein interaction studies were carried out using a bacterial two-hybrid system, and OpuCA was discovered as a TRAP-binding protein. OpuCA is an ATP binding-cytoplasmic (ABC) domain of an OpuC ABC transporter. S. aureus OpuC- mutant strain was constructed and shown to be less tolerant to salt stress, and was defective in choline uptake. OpuC- cells were less pathogenic and showed reduced TRAP phosphorylation and agr activity, did not respond to RAP, and were defective in biofilm formation in vitro and in vivo. These results suggest that OpuC acts as a transporter and also plays a role in S. aureus pathogenesis.
Kiran
Madanahally D
MD
Department of Biological Sciences, Tufts University, Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
Akiyoshi
Donna E
DE
Giacometti
Andrea
A
Cirioni
Oscar
O
Scalise
Giorgio
G
Balaban
Naomi
N
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018441:Biofilms; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D015964:Gene Expression Regulation, Bacterial; D008297:Male; D009154:Mutation; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D016459:Prosthesis-Related Infections / Q000382:microbiology*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D055049:Salt Tolerance; D013211:Staphylococcus aureus / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*; D014882:Water-Electrolyte Balance
D018528:ATP-Binding Cassette Transporters; D048868:Adaptor Proteins, Signal Transducing; C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D002352:Carrier Proteins; C119750:OpuC protein, bacteria; D010750:Phosphoproteins; C428447:RAP protein, Staphylococcus aureus; C428446:TRAP protein, Staphylococcus; D015534:Trans-Activators; D037521:Virulence Factors; D002794:Choline