Alpha-toxin damages the air-blood barrier of the lung in a rat model of Staphylococcus aureus-induced pneumonia.
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We have shown that injury to alveolar epithelial type I cells may account, in part, for damage to the air-blood barrier of the lung in a rat model of Staphylococcus aureus pneumonia. We have also shown that alpha-toxin is an important cause of damage to the air-blood barrier; however, our data suggest that the toxin is not acting directly on alveolar type I cells. (+info)
Bacteremic pneumonia due to Staphylococcus aureus: A comparison of disease caused by methicillin-resistant and methicillin-susceptible organisms.
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We performed a prospective study of all patients with bacteremic pneumonia due to Staphylococcus aureus over a period of 6 years during an outbreak of methicillin-resistant S. aureus (MRSA). Patients with bacteremic pneumonia due to MRSA (32 cases) or methicillin-susceptible S. aureus (MSSA; 54 cases) were compared. The patients with MRSA pneumonia were older and were more likely than those with MSSA pneumonia to have predisposing factors for acquisition of the infection. There were no differences in clinical findings, radiological pattern, or complications in clinical evolution among patients with MRSA and MSSA pneumonia. Mortality was significantly higher among MSSA-infected patients treated with vancomycin than among those treated with cloxacillin (47% vs. none; P<.01). Multivariate analysis (stepwise logistic regression method) showed a relationship between mortality and the following variables: septic shock (odds ratio [OR], 61), vancomycin treatment (OR, 14), and respiratory distress (OR, 8). (+info)
Factors affecting the course and severity of transnasally induced Staphylococcus aureus pneumonia in mice.
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In order to examine several factors that may affect the course and severity of transnasally induced Staphylococcus aureus pneumonia in mice, bacteria were prepared in a free suspension or bound to fetal mouse cells. Immunosuppression was induced in five strains of mice (ICR, C57BL/6, BALB/c, C3H/He and CBA/J) by injection of cyclophosphamide (200 mg/kg body weight), 2 days before infection. Impairment of mucociliary clearance was induced by intranasal instillation of formalin. Mice were then infected with various doses and strains of the organism. Although no significant differences were observed between either form of inoculum, pretreatment with formalin plus cyclophosphamide was associated with a significant increase in lung bacterial counts. In particular, cyclophosphamide treatment was associated with a high mortality in mice infected with several strains of S. aureus irrespective of their toxin production profiles. Histopathological examination demonstrated that in mice treated with formalin plus cyclophosphamide, clusters of bacteria were observed in lung parenchyma, associated with a mild accumulation of inflammatory cells at day 2 and extensive cell infiltration at day 7. CBA/J mice represented the most susceptible strain among those examined, with 10(4)- and 10(2)-fold higher bacterial counts in the lungs at days 3 and 5, respectively. These results indicate that neutropenia and impaired mucociliary clearance are major factors that influence the severity of S. aureus pneumonia in mice. Analysis of the role of genetic background in enhancement of vulnerability to infection is warranted in future studies. (+info)
Effect of viral and bacterial pneumonias on cell-mediated immunity in humans.
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Cell-mediated immunity (CMI) was assessed during infection and after convalescence in 12 patients with influenza pneumonia and 10 patients with bacterial pneumonia. The patients with influenza pneumonia had a marked impairment of skin test reactivity, and their lymphocytes showed a diminished response to phytohemagglutinin and streptokinase-streptodornase stimulation in vitro. Suppression of CMI was related to the severity of the pneumonia. Patients with bacterial pneumonia showed as great a suppression of the response to phytohemagglutinin and streptokinase-streptodornase as the patients with viral pneumonia. All parameters of CMI returned to normal in both groups after convalescence. The depression of CMI could not be related to a decrease in the number of thymus-derived lymphocytes or to serum-suppressive factors in these patients. (+info)
Breast milk transmission of a Panton-Valentine leukocidin-producing Staphylococcus aureus strain causing infantile pneumonia.
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We report on a 38-day-old infant who developed pleuropneumonia due to a Staphylococcus aureus strain responsible for familial furunculosis, which was acquired by maternal breast-feeding. All isolates from the infant and parents were genetically related by randomly amplified polymorphic DNA analysis and produced Panton-Valentine leukocidin. (+info)
Fas/Fas ligand system mediates epithelial injury, but not pulmonary host defenses, in response to inhaled bacteria.
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The Fas/Fas ligand (FasL) system has been implicated in alveolar epithelial cell apoptosis during pulmonary fibrosis and acute respiratory distress syndrome. However, Fas ligation can also lead to cell activation and cytokine production. The goal of this study was to determine the role of the Fas/FasL system in host defenses against Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae. We administered bacteria by aerosolization into the lungs of Fas-deficient (lpr) mice and wild-type (C57BL/6) mice and measured bacterial clearance at 6 and 12 h. One hour prior to euthanasia, the mice received an intraperitoneal injection of human serum albumin (HSA) for alveolar permeability determinations. At all times after bacterial challenges, the lungs of the lpr mice contained similar or lower numbers of bacteria than those of the C57BL/6 mice. Alveolar permeability changes, as determined by bronchoalveolar lavage fluid HSA concentrations, were less severe in the lpr mice 6 h after the challenges. In response to E. coli, the lpr mice had significantly more polymorphonuclear leukocytes (PMN) and macrophage inflammatory protein 2 in the lungs, whereas histopathologic changes were less severe. In contrast, in response to the gram-positive cocci, the lpr animals had similar or lower numbers of PMN. We conclude that the Fas/FasL system contributes to the development of permeability changes and tissue injury during-gram negative bacterial pneumonia. The Fas/FasL system did not have a major role in the clearance of aerosolized bacteria from the lungs at the bacterial doses tested. (+info)
Staphylococcus aureus agr and sarA functions are required for invasive infection but not inflammatory responses in the lung.
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Staphylococcus aureus strains lacking agr- and sarA-dependent gene products or specific MSCRAMM (microbial surface components recognizing adhesive matrix molecules) adhesins were compared for the ability to activate inflammatory responses in the lung. The mutants were evaluated for virulence in a mouse model of pneumonia and by quantifying their ability to stimulate interleukin-8 (IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in respiratory epithelial cells. In a neonatal mouse, only strains with intact agr and sarA loci were consistently associated with invasive, fatal pulmonary infection (P < 0.001) and sarA was specifically required to cause bacteremia (P < 0.001). The agr and/or sarA mutants were, nonetheless, fully capable of producing pneumonia and were as proficient as the wild-type strain in stimulating epithelial IL-8 expression, a polymorphonuclear leukocyte chemokine, in airway cells. In contrast, agr and especially sarA mutants induced less epithelial GM-CSF expression, and MSCRAMM mutants lacking fibronectin binding proteins or clumping factor A, a ligand for fibrinogen, were unable to stimulate epithelial GM-CSF production. The ability to induce IL-8 expression was independent of the adherence properties of intact bacteria, indicating that shed and/or secreted bacterial components activate epithelial responses. While conserved staphylococcal components such as peptidoglycan are sufficient to evoke inflammation and cause pneumonia, the agr and sarA loci of S. aureus are critical for the coordination of invasive infection of the lungs. (+info)
Fibronectin-binding proteins of Staphylococcus aureus are involved in adherence to human airway epithelium.
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This study was designed to investigate the molecular mechanisms of Staphylococcus aureus adherence to human airway epithelium. Using a humanized bronchial xenograft model in the nude mouse and primary cultures of human airway epithelial cells (HAEC), we showed that S. aureus adhered mainly to undifferentiated HAEC whereas weak adherence (11- to 20-fold lower) to differentiated HAEC was observed (P < 0.01). A fibronectin (FN)-binding protein (FnBP)-deficient strain of S. aureus had a fivefold-lower adherence level to undifferentiated HAEC than did the parental strain (P < 0.005), suggesting that S. aureus FN-binding capacity is involved in the adherence to HAEC. We also showed that 97% of 32 S. aureus clinical strains, isolated from the airway secretions of cystic fibrosis patients (n = 18) and patients with nosocomial pneumonia (n = 14), possessed the two fnb genes. The strains from pneumonia patients had a significantly (P < 0.05) higher FN-binding capacity than did the strains from CF patients. This result was confirmed by the expression of FnBPs, investigated by Western ligand affinity blotting. Our results suggest a major role of FnBPs in the colonization of the airways by S. aureus and point to the importance of the adhesin regulatory pathways in the staphylococcal infectious process. (+info)