Unveiling molecular mechanisms of pneumococcal surface protein A interactions with antibodies and lactoferrin.
BACKGROUND
Streptococcus pneumoniae is a Gram-positive bacterium and a major human pathogen. The organism displays on its surface a variety of molecules that are involved in many essential processes including interactions with the tissues and molecules of its human host. A number of such surface molecules are essential virulence factors in disease processes and pathogenesis during all stages of bacterial life.


OBJECTIVE
Here we introduce one such surface protein, pneumococcal surface protein A (PspA), and show its molecular and structural aspects, and underlying mechanism of function at the atomic level as currently understood. The basis of its anti-complementary properties and functional interactions with its ligand, lactoferrin, is discussed. The PspA antigen binding to lactoferrin prevents the bactericidal effect of this human molecule of many functions. This review is focused on new function characterization studies performed during this century (year 2001 and later). Earlier studies on PspA were reviewed by this author in 2001 and 2004 [Jedrzejas MJ. Pneumococcal virulence factors: structure and function. Microbiol Mol Biol Rev, 2001;65:187-207; Jedrzejas MJ. Extracellular virulence factors of Streptococcus pneumoniae. Front Biosci 2004;9:891-914].


CONCLUSIONS
The discovery and understanding of the molecular mechanisms of individual virulence factors, including PspA, are essential to the appreciation of S. pneumoniae function and mechanisms responsible for colonization and invasion of human tissues by this organism. The utilization of a microscopic view at the atomic level provided by structural biology is essential to this process of discovery. The development of new and better cures for the disease might follow as a result of such awareness.
Jedrzejas
Mark J
MJ
Children's Hospital Oakland Research Institute, 5700 Martin Luther King, Jr. Way, Oakland, CA 94609, USA. mjedrzejas@chori.org
D000818:Animals; D000906:Antibodies / Q000737:chemistry* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007781:Lactoferrin / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D013296:Streptococcus pneumoniae / Q000737:chemistry / Q000378:metabolism
D000906:Antibodies; D001426:Bacterial Proteins; C051592:pneumococcal surface protein A; D007781:Lactoferrin