Pneumolysin as a vaccine and drug target in the prevention and treatment of invasive pneumococcal disease.
Streptococcus pneumoniae (the pneumococcus) remains one of the major human pathogens and one of the most common causes of community-acquired pneumonia, otitis media, sinusitis, and meningitis. Aside from the threats posed by emerging antibiotic resistance and infection with the human immunodeficiency virus, the mortality rate among those patients with severe pneumococcal disease who receive seemingly appropriate antimicrobial chemotherapy remains unacceptably high. Because of its involvement in the pathogenesis of invasive disease, pneumolysin, one of the best-characterized virulence factors of the pneumococcus, represents not only a potential vaccine target, but also a target for adjunctive therapy to antibiotics in patients with acute pneumococcal disease. In this paper we review the cytolytic and pro-inflammatory properties of pneumolysin and their involvement in subversion of host defenses and extra-pulmonary dissemination of the pneumococcus, as well as strategies, both immunological and pharmacological, which may counter these harmful activities of the toxin.
Cockeran
Riana
R
Department of Immunology, Faculty of Health Sciences, University of Pretoria and Tshwane Academic Division of the National Health Laboratory Service, Pretoria, South Africa. rcockera@medic.up.ac.za
Anderson
Ronald
R
Feldman
Charles
C
D000890:Anti-Infective Agents / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D011008:Pneumococcal Infections / Q000188:drug therapy* / Q000382:microbiology / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000494:pharmacology; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000382:microbiology / Q000517:prevention & control; D012307:Risk Factors; D013296:Streptococcus pneumoniae / Q000472:pathogenicity*; D013301:Streptolysins / Q000494:pharmacology*; D018074:Vaccines, Conjugate / Q000494:pharmacology
D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D001426:Bacterial Proteins; D022242:Pneumococcal Vaccines; D013301:Streptolysins; D018074:Vaccines, Conjugate; C032290:plY protein, Streptococcus pneumoniae