title: Streptococcus pneumoniae surface protein PcpA elicits protection against lung infection and fatal sepsis.
abstract: Previous studies have suggested that pneumococcal choline binding protein A (PcpA) is important for the full virulence of Streptococcus pneumoniae, and its amino acid sequence suggests that it may play a role in cellular adherence. PcpA is under the control of a manganese-dependent regulator and is only expressed at low manganese concentrations, similar to those found in the blood and lungs. PcpA expression is repressed under high manganese concentrations, similar to those found in secretions. In this study, we have demonstrated that PcpA elicits statistically significant protection in murine models of pneumonia and sepsis. In the model of pneumonia with each of four challenge strains, statistically fewer S. pneumoniae cells were recovered from the lungs of mice immunized with PcpA and alum versus mice immunized with alum only. The immunizations reduced the median CFU by 4- to 400-fold (average of 28-fold). In the model of sepsis using strain TIGR4, PcpA expression resulted in shorter times to become moribund and subcutaneous immunization with PcpA increased survival times of mice infected with wild-type PcpA-expressing pneumococci.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Glover
authors.forename: Susan K
authors.initials: SK
authors.lastname: Hollingshead
authors.forename: David E
authors.initials: DE
authors.lastname: Briles
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism; D001428:Bacterial Vaccines; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism; D002353:Carrier State / Q000517:prevention & control; D015964:Gene Expression Regulation, Bacterial; D047908:Intracellular Signaling Peptides and Proteins; D008345:Manganese; D051379:Mice; D008808:Mice, Inbred CBA; D009305:Nasopharynx / Q000382:microbiology; D011018:Pneumonia, Pneumococcal / Q000517:prevention & control*; D018805:Sepsis / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000378:metabolism*
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C113653:PcpA protein, Streptococcus; D008345:Manganese