Article

The role of flagellin versus motility in acute lung disease caused by Pseudomonas aeruginosa

University of Florida, Gainesville, Florida, United States
The Journal of Infectious Diseases (Impact Factor: 5.78). 08/2007; 196(2):289-96. DOI: 10.1086/518610
Source: PubMed

ABSTRACT The flagellum of Pseudomonas aeruginosa has been implicated in acute pneumonia, and its flagellin is known to cause lung inflammation. However, its proinflammatory role, versus its motility function, as a cause of death by a whole bacterium has not been demonstrated. This issue was examined in a lung model of acute infection using different flagellar mutants. We found that the absence of motility does not significantly alter the LD(50), whereas the production of excess amounts of flagellin lowers it and results in early death. Next, we found that the absence of the Toll-like receptor 5 (TLR5) ligand, flagellin, results in slower clearance of this organism from the lungs and a delay in the time to death. These findings demonstrate the dual role of flagellin in host defense and in disease and suggest that the death in this model may be biphasic with flagellin playing a role early in the disease.

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    • "Depending on the route, dose administered, and the frequency of dosing, acute lung infection with either rapid clearance of the bacteria or acute sepsis and death could take place (George et al., 1991). Using this model, it has been shown that P. aeruginosa must express several key virulence factors (Balloy et al., 2007). A literature survey about acute vs. chronic P. aeruginosa lung infections clearly shows that to induce an infection for more than 1 month, it is necessary to use an immobilizing agent such as agar, agarose, or seaweed alginate together with the bacterial suspension (Iwata and Sato, 1991; Hart et al., 1993; McMorran et al., 2001; Moser et al., 2002). "
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    ABSTRACT: Biological disease models can be difficult and costly to develop and use on a routine basis. Particularly, in vivo lung infection models performed to study lung pathologies use to be laborious, demand a great time and commonly are associated with ethical issues. When infections in experimental animals are used, they need to be refined, defined, and validated for their intended purpose. Therefore, alternative and easy to handle models of experimental infections are still needed to test the virulence of bacterial lung pathogens. Because non-mammalian models have less ethical and cost constraints as a subjects for experimentation, in some cases would be appropriated to include these models as valuable tools to explore host-pathogen interactions. Numerous scientific data have been argued to the more extensive use of several kinds of alternative models, such as, the vertebrate zebrafish (Danio rerio), and non-vertebrate insects and nematodes (e.g., Caenorhabditis elegans) in the study of diverse infectious agents that affect humans. Here, we review the use of these vertebrate and non-vertebrate models in the study of bacterial agents, which are considered the principal causes of lung injury. Curiously none of these animals have a respiratory system as in air-breathing vertebrates, where respiration takes place in lungs. Despite this fact, with the present review we sought to provide elements in favor of the use of these alternative animal models of infection to reveal the molecular signatures of host-pathogen interactions.
    Frontiers in Microbiology 02/2015; 6:38. DOI:10.3389/fmicb.2015.00038 · 3.94 Impact Factor
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    • "Two surface organelles, flagella and type IV pili (tfp), affect virulence in acute and chronic models of Pseudomonas disease. Bacteria lacking flagella caused less inflammation and death than wild-type counterparts in a murine model of acute pneumonia (Feldman et al., 1998), possibly a reflection of flagellin's ability to trigger pro-inflammatory host responses via Toll-like receptor 5 rather than to a loss of motility per se (Balloy et al., 2007). Flagella are required for robust biofilm formation (Klausen et al., 2003), and likely contribute to persistent colonization. "
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    Journal of Medical Microbiology 05/2010; 59(Pt 5):511-20. DOI:10.1099/jmm.0.017715-0 · 2.27 Impact Factor
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    ABSTRACT: Respiratory tract infections (RTI), presenting as common cold, pharyngitis, tonsillitis, acute otitis media, bronchitis or pneumonia are a major health problem in children. In this thesis common environmental and host factors, as well as plausible genetic factors were evaluated in a large birth cohort study in the Netherlands for their effect on frequent RTI in children. We explored the relationship between frequent RTI, atopy, exposure to environmental tobacco smoke (ETS), and the interaction between the later two in relation to susceptibility to RTI. We showed that children with intrauterine exposure to ETS who also exhibited early markers of atopy (high neonatal total IgE or symptoms of atopic dermatitis) had an increased risk for frequent RTI in preschool years. By contrast, intrauterine ETS exposure was unrelated to frequent RTI in children without these early markers of atopy. The potential association between atopy on its own and frequent RTI was also explored. We found that serum IgE and skin prick test were related to frequent RTI in school-aged children from allergic mothers. These findings suggest that atopy might affect susceptibility to RTI in some children, but the effect seems to be limited to high-risk children with a family predisposition for atopy. The second part of this thesis focused on the influence of genetic variation in innate immunity pathways on susceptibility to RTI during preschool years. We showed that polymorphisms or haplotypes of the MBL gene and the genes encoding Ficolin-2 and Ficolin-3, are not associated with frequent RTI. By contrast, minor alleles of polymorphisms in Toll-like receptor (TLR) genes TLR4 and TLR5 were shown to be associated, in a dose-responsive matter, with an increased risk of frequent RTI. Interestingly, maternal allergy, which is one of the features commonly used as risk factor for atopy in the child itself, seemed to modify the effect of variation in TLR genes on RTI frequency. Finally, we used previous findings combined with well-known environmental risk factors in order to develop a prediction rule for frequent RTI. We found that adequate prediction of frequent RTI in preschool years in our population is accomplished neither by using questionnaire-derived variables, genetic variables nor by a combination of both. Future epidemiological research into the background of RTI in children should focus on gene-gene interactions between innate immunity genes related to both infectious and atopic phenotypes. Interactions between genes and environmental factors such as exposure to ETS should also be taken into account. Therefore, large population-based cohort studies are required with a well defined RTI phenotype based on questionnaire-information on symptoms and doctor’s diagnosis of RTI, next to pathogen identification. Finally, we should make an effort to combine epidemiological and genetic data in upcoming prognostic studies, and to translate genetic data into preventive or therapeutic interventions, which at present is not realized in clinical practice.
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