Pathogenesis of pneumococcal pneumonia.
Pneumococcal pneumonia is the most severe of the common community-acquired pulmonary infections. The recent release of the complete DNA sequence reveals the entire capability of the bacteria and the current challenge is to map gene products to the mechanics of disease. This process will reveal antibiotic targets and protein vaccine candidates crossing serotype boundaries. Choline is a major constituent of surfactant and it is also a required nutrient for the pneumococcus. It appears that choline incorporated into the cell wall can bind the bacteria to the receptor for platelet activating factor, the gateway to invasion. The choline also serves as an antenna to which multifunctional proteins dock, thereby decorating the bacterial surface. This set of 12 choline binding proteins is subject to phase variation of expression resulting in display of different combinations of proteins that adapt the bacteria to survival on the mucosa versus the blood stream. These changes affect protective antigens, adhesions, and lytic proteins tying together the major elements of pneumococcal physiology: natural DNA transformation, adherence and invasion of host cells, and autolysis. Taking these components and building an understanding of disease is challenging. Clearly, the toxin pneumolysin is a major mediator of cell damage in the lung. Inflammation is also incited by cell wall components. The signal transduction pathways that explain pneumococcal inflammation are more complex than those for gram-negative endotoxin.
Novak
R
R
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Tuomanen
E
E
D000818:Animals; D017714:Community-Acquired Infections / Q000453:epidemiology / Q000382:microbiology; D006094:Gram-Positive Bacteria / Q000378:metabolism; D006801:Humans; D007964:Leukocytosis / Q000276:immunology; D009305:Nasopharynx / Q000382:microbiology; D011018:Pneumonia, Pneumococcal / Q000453:epidemiology / Q000382:microbiology* / Q000503:physiopathology*; D011379:Prognosis; D011650:Pulmonary Alveoli / Q000276:immunology / Q000382:microbiology; D018570:Risk Assessment; D012720:Severity of Illness Index