Burkholderia cepacia complex (BCC) is a group of phenotypically-related bacteria which are responsible for devastating infection in certain compromised hosts. These bacteria, initially named Pseudomonas cepacia, were recognized as particularly virulent in some patients with cystic fibrosis (CF) about 30 years ago.  Since that initial report from Toronto, other studies have also demonstrated that BCC can cause rapidly fatal, septicemic infection in CF patients, the so-called “cepacia syndrome.” This illness is markedly different from that caused by the more common Pseudomonas aeruginosa, which almost never causes bacteraemia, and is generally associated with a less rapid decline in pulmonary function. BCC infections in CF are particularly problematic because infection can spread among patients, even with casual social contact. BCC also cause devastating infection in patient with chronic granulomatous disease (CGD), a defect in phagocytic killing in which neutrophils fail to generate toxic reactive oxygen intermediates. BCC have recently emerged as the most common cause of fatal bacterial infection in CGD. Common features between CF and CGD that predispose patients to BCC infection have not been indentified but may be failure to deliver reactive oxygen intermediates to the site of infection. BCC infections are particularly challenging to treat because of their constitutive resistance to antimicrobial therapy, particularly aminoglycosides. The bacteria are also resistant to phagocytic nonoxidative killing, explaining their extraordinary virulence in CGD. Virulence determinants of the BCC have been sought by many investigators, but none has been identified to explain the potential for invasive and devastating infection. We and others have recently demonstrated that BCC can grow as either mucoid or nonmucoid. It appears that the nonmucoid variants are associated with more serious disease in CF than isogenic mucoid variants. Studies are currently underway to determine the factors associated with the nonmucoid form that predispose to such serious disease.

Staphylococcus aureus is an important cause of pneumonia, especially the necrotizing pneumonias that are being seen increasingly after influenza infection. As these most often occur in well children and adolescents, it is unclear exactly how or why these infections occur. Using a mouse model of pneumonia, we found that there was significantly increased mortality in mice co-infected with both S. aureus and influenza, as compared to those infected with either the virus or the bacteria alone. We have studied the role of the major virulence factor, protein A in the pathogenesis of Staphylococcal pneumonia. This bacterial surface protein binds to the TNF receptor on the surface of airway cells and stimulates the TNF cascade causing severe inflammation. In addition, protein A also binds to the EGFR and stimulates the expression of the type I interferon cascade. This signaling system is a critical component of the host defense against influenza. Unfortunately, the activation of Interferon-beta and the rest of this signaling system enhance the ability of the S. aureus to cause severe pneumonia. S. aureus protein A also activates changes in the cytoskeleton of mucosal epithelial cells. Again, through the protein A-TNFR1 interaction, RhoA GTPAse is activated resulting in the opening of the epithelial tight junctions which enables these non-motile organisms to transmigrate across the mucosal surface and reach binding sites in the subepithelial matrix components, establishing a nidus of infection. Thus, this surface protein of staphylococci contributes substantially to the ability of these bacteria to cause invasive infection in the lung. 

Pseudomonas aeruginosa has emerged worldwide as a major pathogen causing nosocomial infections such as bloodstream infection, ventilator-associated pneumonia, and wound infection, particularly in critical patients admitted in the intensive care units. P. aeruginosa, however,was not previously recognized as an enteric infection agent, and rarely causing life threatening events, except in patients with immunocompromised status, cystic fibrosis (CF), and hematological, malignant, or other chronic diseases. In Taiwan, P. aeruginosa sepsis had been documented to occur in the community setting, and usually affected infants without underlying diseases. Community-acquired P. aeruginosa infection could result in intestinal perforation, peritonitis and even fatality in previously healthy infants, presumably due to the initial administration of an inappropriate antibiotic regimen. The mechanism of community-acquired P. aeruginosa infection in non-CF patients has not been evaluated. In this presentation, I will report the clinical characteristics of community-acquired pseudomonas enterocolitis and sepsis in previously healthy infants. We also sought to explore the microbial virulence factors associated with such infection in Taiwan.