The role of flagellin versus motility in acute lung disease caused by Pseudomonas aeruginosa
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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ABSTRACT: Type IV pili (TFPs) are required for bacterial twitching motility and for phage infection in the opportunistic human pathogen Pseudomonas aeruginosa. Here we describe a phage-encoded protein, D3112 protein gp05 (hereafter referred to as Tip, representing twitching inhibitory protein), whose expression is necessary and sufficient to mediate the inhibition of twitching motility. Tip interacts with and blocks the activity of bacterial-encoded PilB, the TFP assembly/extension ATPase, at an internal 40-aa region unique to PilB. Tip expression results in the loss of surface piliation. Based on these observations and the fact that many P. aeruginosa phages require TFPs for infection, Tip-mediated twitching inhibition may represent a generalized strategy for superinfection exclusion. Moreover, because TFPs are required for full virulence, PilB may be an attractive target for the development of novel antiinfectives.Proceedings of the National Academy of Sciences 07/2014; DOI:10.1073/pnas.1403537111 · 9.81 Impact Factor
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ABSTRACT: Development of an easy sustainable synthetic pathway towards oxide nanomaterials (NMs) is a necessary challenge for nanotechnology research workers. Additionally, antimicrobial activity of oxide nanoparticles against multi drug resistance pathogenic bacteria motivates scientists to focus their research on oxide materials. We report here a cost effective, simple and eco-friendly pathway of synthesizing NiO nanoparticles (NPs). X-ray diffraction and energy dispersive X-ray study confirmed their crystallinity and composition. Field emission scanning electron microscope (FESEM) was employed to understand their surface architecture and the dimension of synthesized NiO NPs were found to be 20-30 nm from transmission electron microscope (TEM) study. The as synthesized NiO demonstrated typical spin glass behaviour which is one advantage of our synthetic procedure. Antimicrobial properties of NiO NPs were investigated using Gram negative and Gram positive bacteria and their bactericidal effects were determined from minimum inhibitory concentrations (MIC) and Minimum bactericidal concentrations (MBC). Haemolytic activity revealed the nontoxic nature of the NPs towards the blood proteins at MBC. TEM images of bacteria cells treated with NiO NPs showed irreversible damages to the cell wall leading to cell death. In light of our findings a possible mechanism of the antimicrobial effect of NiO NPs has been proposed.RSC Advances 01/2013; 3(42):19348. DOI:10.1039/c3ra42628a · 3.71 Impact Factor
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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.