Cavitary pneumonia in an AIDS patient caused by an unusual Bordetella bronchiseptica variant producing reduced amounts of pertactin and other major antigens.
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Although Bordetella bronchiseptica can infect and colonize immunocompromised humans, its role as a primary pathogen in pneumonia and other respiratory processes affecting those patients remains controversial. A case of cavitary pneumonia caused by B. bronchiseptica in an AIDS patient is presented, and the basis of the seemingly enhanced pathogenic potential of this isolate (designated 814) is investigated. B. bronchiseptica was the only microorganism recovered from sputum, bronchoalveolar lavage fluid, and samples taken through the protected brush catheter. Unlike previous work reporting the involvement of B. bronchiseptica in cases of pneumonia, antibiotic treatment selected on the basis of in vitro antibacterial activity resulted in clearance of the infection and resolution of the pulmonary infiltrate. Although isolate 814 produced reduced amounts of several major antigens including at least one Bvg-activated factor (pertactin), the molecular basis of this deficiency was found to be BvgAS independent since the defect persisted after the bvgAS locus of isolate 814 was replaced with a wild-type bvgAS allele. Despite its prominent phenotype, isolate 814 displayed only a modest yet a significant deficiency in its ability to colonize the respiratory tracts of immunocompetent rats at an early time point. Interestingly, the antibody response elicited by isolate 814 in these animals was almost undetectable. We propose that isolate 814 may be more virulent in immunocompromised patients due, at least in part, to its innate ability to produce low amounts of immunogenic factors which may be required at only normal levels for the interaction of this pathogen with its immunocompetent natural hosts. (+info)
BhuR, a virulence-associated outer membrane protein of Bordetella avium, is required for the acquisition of iron from heme and hemoproteins.
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Iron (Fe) is an essential element for most organisms which must be obtained from the local environment. In the case of pathogenic bacteria, this fundamental element must be acquired from the fluids and tissues of the infected host. A variety of systems have evolved in bacteria for efficient acquisition of host-bound Fe. The gram-negative bacterium Bordetella avium, upon colonization of the avian upper respiratory tract, produces a disease in birds that has striking similarity to whooping cough, a disease caused by the obligate human pathogen Bordetella pertussis. We describe a B. avium Fe utilization locus comprised of bhuR and six accessory genes (rhuIR and bhuSTUV). Genetic manipulations of B. avium confirmed that bhuR, which encodes a putative outer membrane heme receptor, mediates efficient acquisition of Fe from hemin and hemoproteins (hemoglobin, myoglobin, and catalase). BhuR contains motifs which are common to bacterial heme receptors, including a consensus FRAP domain, an NPNL domain, and two TonB boxes. An N-terminal 32-amino-acid segment, putatively required for rhuIR-dependent regulated expression of bhuR, is present in BhuR but not in other bacterial heme receptors. Two forms of BhuR were observed in the outer membrane of B. avium: a 91-kDa polypeptide consistent in size with the predicted mature protein and a smaller 82-kDa polypeptide which lacks the 104 amino acids found at the N terminus of the 91-kDa form. A mutation in hemA was engineered in B. avium to demonstrate that the bacterium transports heme into the cytoplasm in a BhuR-dependent manner. The role of BhuR in virulence was established in turkey poults by use of a competitive-infection model. (+info)
Nonpeptide antagonists of AT1 receptor for angiotensin II delay the onset of acute respiratory distress syndrome.
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We have previously reported that losartan, a selective antagonist of AT1 receptors for angiotensin II (AII), strongly suppresses the activation of neutrophils by N-formylmethionyl-leucyl-phenylalanine (fMLP) through a mechanism that does not involve inhibition of AT1 receptors. Herein, we analyze whether losartan would prevent the development of the acute respiratory distress syndrome (ARDS) triggered by lung bacterial infection. We found that losartan (0.2-200 microg/kg/min) delays the onset of ARDS in Wistar rats challenged by i.t. instillation of Bordetella bronchiseptica. Although this effect was associated with a significant inhibition of lung-neutrophil recruitment, lung bacterial clearance was not impaired but rather, it was significantly improved. We also found that another nonpeptide AT1 receptor blocker, irbesartan, exerted similar effects to losartan, i.e., it was also able to inhibit neutrophil activation by fMLP and to delay the onset of ARDS in B. bronchiseptica-challenged rats. Neither the inhibitor of angiotensin-converting enzyme captopril, nor the nonselective peptide inhibitor of AII receptors saralasin reproduced these effects. Our data are consistent with the possibility that nonpeptide AT1 receptor blockers delay the onset of ARDS triggered by bacterial infection through a mechanism dependent, at least in part, on their ability to prevent neutrophil activation by N-formyl-peptides. (+info)
Role of Bordetella O antigen in respiratory tract infection.
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Lipopolysaccharide (LPS), as the major surface molecule of gram-negative bacteria, interacts with the host in complex ways, both inducing and protecting against aspects of inflammatory and adaptive immunity. The membrane-distal repeated carbohydrate structure of LPS, the O antigen, can prevent antibody functions and may vary as a mechanism of immune evasion. Genes of the wbm locus are required for the assembly of O antigen on the animal pathogen Bordetella bronchiseptica and the human pathogen B. parapertussis. However, the important human pathogen B. pertussis lacks these genes and a number of in vitro and in vivo characteristics associated with O antigen in other organisms. To determine the specific functions of O antigen in these closely related Bordetella subspecies, we compared wbm deletion (Deltawbm) mutants of B. bronchiseptica and B. parapertussis in a variety of assays relevant to natural respiratory tract infection. Complement was not activated or depleted by wild-type bordetellae expressing O antigen, but both Deltawbm mutants activated complement and were highly sensitive to complement-mediated killing in vitro. Although the O-antigen structures appear to be substantially similar, the two mutants differed strikingly in their defects within the respiratory tract. The B. parapertussis Deltawbm mutant was severely defective in colonization of the tracheas and lungs of mice, while the B. bronchiseptica Deltawbm mutant showed almost no defect. While in vitro characteristics such as serum resistance may be attributable to O antigen directly, the role of O antigen during infection appears to be more complex, possibly involving factors differing among the closely related bordetellae or different interactions between each one and its host. (+info)
Role of systemic and mucosal immune responses in reciprocal protection against Bordetella pertussis and Bordetella parapertussis in a murine model of respiratory infection.
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The roles of systemic humoral immunity, cell-mediated immunity, and mucosal immunity in reciprocal protective immunity against Bordetella pertussis and Bordetella parapertussis were examined by using a murine model of respiratory infection. Passive immunization with serum from mice infected with B. pertussis established protective immunity against B. pertussis but not against B. parapertussis. Protection against B. parapertussis was induced in mice that had been injected with serum from mice infected with B. parapertussis but not from mice infected with B. pertussis. Adoptive transfer of spleen cells from mice infected with B. pertussis or B. parapertussis also failed to confer reciprocal protection. To examine the role of mucosal immunity in reciprocal protection, mice were infected with preparations of either B. pertussis or B. parapertussis, each of which had been incubated with the bronchoalveolar wash of mice that were convalescing after infection with B. pertussis or B. parapertussis. Such incubation conferred reciprocal protection against B. pertussis and B. parapertussis on infected mice. The data suggest that mucosal immunity including secreted immunoglobulin A in the lungs might play an important role in reciprocal protective immunity in this murine model of respiratory infection. (+info)
Role of adhesin release for mucosal colonization by a bacterial pathogen.
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Pathogen attachment is a crucial early step in mucosal infections. This step is mediated by important virulence factors called adhesins. To exert these functions, adhesins are typically surface-exposed, although, surprisingly, some are also released into the extracellular milieu, the relevance of which has previously not been studied. To address the role of adhesin release in pathogenesis, we used Bordetella pertussis as a model, since its major adhesin, filamentous hemagglutinin (FHA), partitions between the bacterial surface and the extracellular milieu. FHA release depends on its maturation by the specific B. pertussis protease SphB1. We constructed SphB1-deficient mutants and found that they were strongly affected in their ability to colonize the mouse respiratory tract, although they adhered even better to host cells in vitro than their wild-type parent strain. The defect in colonization could be overcome by prior nasal instillation of purified FHA or by coinfection with FHA-releasing B. pertussis strains, but not with SphB1-producing FHA-deficient strains, ruling out a nonspecific effect of SphB1. These results indicate that the release of FHA is important for colonization, as it may facilitate the dispersal of bacteria from microcolonies and the binding to new sites in the respiratory tract. (+info)
Role of antibodies in immunity to Bordetella infections.
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The persistence of Bordetella pertussis and B. parapertussis within vaccinated populations and the reemergence of associated disease highlight the need to better understand protective immunity. The present study examined host immunity to bordetellae and addressed potential concerns about the mouse model by using a comparative approach including the closely related mouse pathogen B. bronchiseptica. As previously observed with B. pertussis, all three organisms persisted throughout the respiratory tracts of B-cell-deficient mice, indicating that B cells are required for bacterial clearance. However, adoptively transferred antibodies rapidly cleared B. bronchiseptica but not human pathogens. These results obtained with the mouse model are consistent with human clinical observations, including the lack of correlation between antibody titers and protection, as well as the limited efficacy of intravenous immunoglobulin treatments against human disease. Together, this evidence suggests that the mouse model accurately reflects substantial differences between immunities to these organisms. Although both B. pertussis and B. parapertussis are more closely related to B. bronchiseptica than they are to each other, they share the ability to resist rapid clearance from the lower respiratory tract by adoptively transferred antibodies, an adaptation that correlates with their emergence as human pathogens that circulate within vaccinated populations. (+info)
Comparison of ribotyping and restriction enzyme analysis for inter- and intraspecies discrimination of Bordetella avium and Bordetella hinzii.
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Bordetella avium is an avian respiratory disease pathogen responsible for substantial economic losses to the turkey industry. The inability to distinguish isolates has hampered outbreak investigations and prevents a complete understanding of transmission mechanisms. Isolates of Bordetella hinzii, often referred to as B. avium-like or as Alcaligenes faecalis type II prior to 1995, have also been acquired from the respiratory tracts of diseased poultry but are not believed to be pathogenic for birds. Therefore, differentiating between B. avium and B. hinzii is of importance for veterinary diagnostic laboratories. It was recently reported that both PvuII ribotyping and HinfI/DdeI restriction endonuclease analysis (REA) show promise for distinguishing isolates of B. avium and B. hinzii. Here we compare the ability of these techniques to discern inter- and intraspecies differences. While both approaches distinguished numerous types within a species, only REA was sufficiently discriminatory for routine use as an epidemiologic tool. Both techniques clearly distinguish between B. avium and B. hinzii, although the results of ribotyping are more easily interpreted. Ribotyping and REA identified numerous, previously unrecognized B. hinzii strains from a collection of bordetella isolates, including one acquired from a rabbit. This is the first report of B. hinzii isolation from a nonhuman mammalian species. At least some of the newly recognized B. hinzii isolates have been previously reported to cause disease in poults, suggesting that the pathogenicity of this agent for poultry should be more rigorously examined. (+info)