The opportunistic bacterium Pseudomonas aeruginosa causes chronic respiratory infections in cystic fibrosis and immunocompromised individuals. Bacterial adherence to the basolateral domain of the host cells and internalization are thought to participate in P. aeruginosa pathogenicity. However, the mechanism by which the pathogen initially modulates the paracellular permeability of polarized respiratory epithelia remains to be understood. To investigate this mechanism, we have searched for virulence factors secreted by P. aeruginosa that affect the structure of human airway epithelium in the early stages of infection. We have found that only bacterial strains secreting rhamnolipids were efficient in modulating the barrier function of an in vitroreconstituted human respiratory epithelium, irrespective of their release of elastase and lipopolysaccharide. In contrast to previous reports, we document that P. aeruginosa was not internalized by epithelial cells. We further report that purified rhamnolipids, applied on the surfaces of the epithelia, were sufficient to functionally disrupt the epithelia and to promote the paracellular invasion of rhamnolipid-deficient P. aeruginosa. The mechanism involves the incorporation of rhamnolipids within the host cell membrane, leading to tight-junction alterations. The study provides direct evidence for a hitherto unknown mechanism whereby the junctiondependent barrier of the respiratory epithelium is selectively altered by rhamnolipids.The airway mucosa is an efficient barrier to protect the host from infection by pathogens. An essential component of this barrier is the polarity of surface epithelial cells, which allows them to segregate the receptors that trigger the adherence and internalization of several pathogens within the basolateral domain of the membrane (51). Normally, this domain is not accessible to microbial organisms, due to the presence of tight junctions (TJ) that separate the apical from the basolateral membrane components and seal the paracellular space (37). To overcome this protective barrier, several microorganisms have developed strategies to alter either the apical membrane of epithelial cells (39) or the TJ barrier (53). Understanding the mechanism underlying these alterations is a prerequisite for development of novel therapeutic strategies targeted to specific molecular and cellular events. This is particularly necessary in the context of infections, such as those caused by Pseudomonas aeruginosa, which is difficult to eradicate by conventional antibiotic treatments (45).P. aeruginosa is an opportunistic gram negative bacterium that does not invade normal mucosae but causes serious nosocomial infections in immunocompromised individuals and in cystic fibrosis patients (7). The pathogenic mechanism accounting for these infections is not fully clarified and has been variously attributed to the production of different cell-associated and secreted virulence factors (41). The finding that P. aeruginosa is internalized more readily by dispersed and migrating ...

Severe infections due to Staphylococcus aureus require prolonged therapy for cure, and relapse may occur even years after the first episode. Persistence of S. aureus may be explained, in part, by nasal carriage of S. aureus, which occurs in a large percentage of healthy humans and represents a major source of systemic infection. However, the persistence of internalized S. aureus within mucosal cells has not been evaluated in humans. Here, we provide the first in vivo evidence of intracellular reservoirs of S. aureus in humans, which were assessed in endonasal mucosa specimens from patients suffering from recurrent S. aureus rhinosinusitis due to unique, patient-specific bacterial clonotypes. Heavily infected foci of intracellular bacteria located in nasal epithelium, glandular, and myofibroblastic cells were revealed by inverted confocal laser scan fluorescence and electron microscopic examination of posttherapy intranasal biopsy specimens from symptom-free patients undergoing surgery on the sinuses. Intracellular residence may provide a sanctuary for pathogenic bacteria by protecting them from host defense mechanisms and antibiotic treatment during acute, recurrent S. aureus rhinosinusitis.

Many patients with olfactory dysfunction not only experience quantitative reduction of olfactory function, but also suffer from distorted olfactory sensations. This qualitative dysfunction is referred to as parosmia (also called "troposmia") or phantosmia, with the major difference that distorted olfactory sensations are experienced in the presence or absence of an odor, respectively. Our clinical observations corroborate the literature in terms of a general underestimation of the incidence of olfactory distortions. Based on selected cases we try to show that olfactory distortions exhibit a large variance in their clinical appearance. Further, emphasis is placed on the fact that only a detailed and directed history of the patient can provide cues to the correct diagnosis.

Plasma immunoreactive endothelin-1 concentrations were determined by radioimmunoassay in 11 septic patients during the first 24 hours after the development of the sepsis syndrome in 15 nonseptic postoperative patients studied 24 hours after open heart surgery and in 14 healthy volunteers. Mean endothelin-1 plasma concentrations were significantly (p less than 0.001) increased in septic patients (19.9 +/- 2.2 pg/mL, mean +/- standard error) compared to concentrations found in postoperative cardiac patients (11.9 +/- 0.7 pg/mL) or in healthy volunteers (6.1 +/- 0.3 pg/mL). In septic patients elevated plasma concentrations of endothelin-1 were inversely correlated with cardiac index (r = -0.80, p less than 0.005) and positively correlated the severity of illness as documented by APACHE II score (r = 0.74, p less than 0.01) and plasma creatinine levels (r = 0.80, p less than 0.005). No such correlations were found in postoperative cardiac patients. These results indicate that endothelin-1 concentrations are correlated with the severity of illness and depression of cardiac output in patients with sepsis.