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: 6). 08/2007; 196(2):289-96. DOI: 10.1086/518610
Source: PubMed


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 LD50 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.
    Full-text · Article · Feb 2015 · Frontiers in Microbiology
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    • "An initial step in biofilm formation is bacterial attachment to a surface depends on two surface organelles, flagella and type IV pili (tfp). Bacteria lacking flagella caused less inflammation [6], and are required for robust biofilm formation [7,8], and likely contribute to persistent colonization. Type IV pili, which power twitching motility across solid surfaces [9], mediate attachment to epithelial cells, and contribute to biofilm formation [10]. "

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    • "The well known paradox is that the TLR5-flagellin interaction is a major mediator of inflammation following exposure to Pa. Indeed, Pa mutants which overproduced flagellin, caused severe inflammation [31]. The consequence is that some authors have proposed TLR5 as an anti-inflammatory target [32]. "
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    ABSTRACT: Background The aim was to measure flagellin concentrations in the expectorations of CF patients and to examine whether there are correlations with the level of respiratory insufficiency and inflammation. Methods Sputum samples from 31 adult patients chronically colonized with P. aeruginosa were collected and analysed for their content of flagellin and IL-8. Clinical data were extracted from patient files. Results Regardless of whether patients are colonized with mucoid strains or not, they carry clones of P. aeruginosa that express flagellin. While flagellin was present in airways of all of our CF patients, it is difficult to ascertain its contribution to inflammation (IL-8) and lung function deterioration. Conclusions This is the first demonstration that flagellin is present in the sputum of patients. Thus, attempts to down regulate inflammation by the use of TLR5 (flagellin receptor) antagonists remain a possibility. However, this result needs to be extended to a larger number of patients to validate it for future research on this subject.
    Full-text · Article · Jun 2014 · BMC Pulmonary Medicine
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