Casadevall A, et al. 1994. has also become familiar with the practice of passive immunization for the treatment of a variety of infections that include tetanus and rabies. The downside of antibody therapy, a form of Rabbit polyclonal to EIF4E hypersensitivity known as serum sickness that develops after exposure to heterologous immunoglobulins (i.e., from other species), is also well-known. Antibodies have been used in a diagnostic capacity for many diseases and for identifying serotypes within single species of pathogens (including distinguishing between the multiple capsular polysaccharide serotypes of (3, 4), and direct antimicrobial effects on gene expression in fungi (5), among others. As mentioned above, antibodies are used to identify the serotypes of that are critical for the formulation of the current pneumococcal vaccines. The most effective type of host response to is centered on antibody binding to the pneumococcal capsular polysaccharide followed by Fc receptor-mediated phagocytosis. Moreover, this traditional mechanism of opsonization-phagocytosis is Trimebutine maleate also thought to be essential for the response to active immunization with both the 7- and 23-valent pneumococcal capsular polysaccharide vaccines (6). In contrast to the traditional understanding that opsonization-phagocytosis is necessary for pneumococcal clearance, we now know that there are a number of nonopsonic antibodies to the capsular polysaccharides that have the capacity to protect both experimentally and clinically. A number of these nonopsonic antibodies have been identified and are both polyclonal and monoclonal, can be derived from humans and mice, and protect against pneumonia and sepsis in experimental models. So, how do these nonopsonic antibodies work? The study by Yano and coworkers in the laboratory of Liise-anne Pirofski published in (7) identifies one mechanism that was heretofore unappreciated: the Trimebutine maleate nonopsonic antibodies enhance the transformation competence of two serotypes, which leads to an overall increase in genetic exchange and bacterial variability and sharply lowers the number of organisms. While the bactericidal end result has obvious therapeutic relevance, the road taken to elucidate this mechanism is also of much biological interest and one that crisscrosses microbiology and immunology at many points. A protective nonopsonic monoclonal antibody (1E2, 1gG1k specific for serotype 3) induced a higher transformation frequency in the appropriate strains when Trimebutine maleate added to competence-stimulating peptide (CSP) than CSP alone or the other opsonic subclass-matched monoclonal antibodies that were used as controls. Moreover, a human monoclonal nonopsonic IgM had the same effect as 1E2, indicating that this mechanism is not specific to the immunoglobulin class. Similar effects obtained with antibodies to serotype 8 also showed that the induction of transformation efficiency could be obtained with more than one pathogenic strain of pneumococcus and with antibodies derived from both human and mouse hybridomas. Agglutination of the pneumococcus appeared to be a factor in the induction of higher transformation frequency. Interestingly, agglutination, at least in for interbacterial communication through the activation of the Com pathway that regulates genetic transformation and therefore induces competence in these bacteria, the physiological state that allows incorporation of exogenous DNA. In general, CSP released into the medium activates a two-component system (ComDE) that results in the expression of expression after 8?minutes of incubation, representing a new second wave of expression that followed the peak expression induced by CSP alone after 2?min. The entire process of competence development in occurs rapidly, within 15?minutes, a period of time that can easily encompass the 2- and 8-min observation of upregulation of in organisms exposed to CSP and the nonopsonic antibody in the Yano et al. study (7). Likewise, the and the production of lytic factors that are capable of eliminating the cells that do not become competent following exposure to CSP (7). Eliminating noncompetent cells supports the idea that permissiveness to accept exogenous DNA is the preferred.