title: Lipoprotein PsaA in virulence of Streptococcus pneumoniae: surface accessibility and role in protection from superoxide.
abstract: PsaA of Streptococcus pneumoniae, originally believed to be an adhesin, is the lipoprotein component of an Mn2+ transporter. Mutations in psaA cause deficiencies in growth, virulence, adherence, and the oxidative stress response. Immunofluorescence microscopy shows that PsaA is hidden beneath the cell wall and the polysaccharide capsule and only exposed to antibodies upon cell wall removal. A psaBC deletion mutant, expressing PsaA normally, was as deficient in adherence to Detroit 562 cells as were strains lacking PsaA. Thus, PsaA does not appear to act directly as an adhesin, but rather, psaA mutations indirectly affect this process through the disruption of Mn2+ transport. The deficiency in Mn2+ transport also causes hypersensitivity to oxidative stress from H2O2 and superoxide. In a chemically defined medium, growth of the wild-type strain was possible in the absence of Fe2+ and Mn2+ cations after a lag of about 15 h. Addition of Mn2+ alone or together with Fe2+ allowed prompt and rapid growth. In the absence of Mn2+, the addition of Fe2+ alone extended the 15-h lag phase to 25 h. Thus, while Fe2+ adversely affects the transition from lag phase to log phase, perhaps through increasing oxidative stress, this effect is relieved by the presence of Mn2+. A scavenger specific for superoxides but not those specific for hydroxyl radicals or H2O2 was able to eliminate the inhibition of growth caused by iron supplementation in the absence of Mn2+. This implies that superoxides are a key player in oxidative stress generated in the presence of iron.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Johnston
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Myers
authors.forename: Martina M
authors.initials: MM
authors.lastname: Ochs
authors.forename: William H
authors.initials: WH
authors.lastname: Benjamin
authors.forename: David E
authors.initials: DE
authors.lastname: Briles
authors.forename: Susan K
authors.initials: SK
authors.lastname: Hollingshead
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D018829:Adhesins, Bacterial; D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D008808:Mice, Inbred CBA; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D011008:Pneumococcal Infections / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity*; D013481:Superoxides / Q000378:metabolism*; D014774:Virulence / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; C045076:Fenton's reagent; D008074:Lipoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C085000:PsaA protein, Streptococcus; C115936:psaB protein, Streptococcus; C115937:psaC protein, Streptococcus; D013481:Superoxides; D008345:Manganese; D006861:Hydrogen Peroxide; D007501:Iron