Interaction of Gram-Positive Microorganisms with Complement

Gram-positive bacteria present a remarkable contrast in many ways to the gramnegative organisms that are the subject of the other papers in this volume. The complex outer membrane of the gram-negative organisms, which is the focus of complement attack, does not exist for those that are gram positive. Rather, the peptidoglycan layer, which underlies the outer membrane in gramnegative organisms, is very often the outermost structure of the gram-positive bacteria. In general, this peptidoglycan is very hypertrophied in gram-positive bacteria — its thickness in Streptococcus pneumoniae, for example, can reach 160 nm as opposed to an average thickness of perhaps only 3 nm in enteric gram-negative organisms. It is this very thick cell wall, which is responsible for the retention of gentian violet by these organisms during gram staining, that defines them as gram positive. This cell wall can act as a barrier to attack by the lytic components of complement. In general, therefore, gram-positive organisms are not directly killed by complement and are defined as serum resistant. The mechanism of serum resistance, however, differs for gram-positive and gram-negative bacteria, and the serum resistance of the gram-positive bacteria is critically dependent on their thick peptidoglycan layer. For example, although a C5b-9 membrane attack complex forms normally on the pneumococcal surface and apparently inserts normally into the cell wall, the peptidoglycan layer is too thick for the C5b-9 to reach the plasma membrane of gram-positive organisms (Joiner et al. 1983).