Experimental Studies of the Pathogenesis of Infections Due to Pseudomonas aeruginosa: Description of a Burned Mouse Model

Stieritz, Donald D.; Holder, Ian Alan

doi:10.1093/infdis/131.6.688

Cited by 257 publications

(157 citation statements)

References 17 publications

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“…Thermal injury and infection were carried out as described (36,37). Brief ly, mice were infected with 2 ϫ 10 6 wild-type and mutant P. aeruginosa, and the surviving mice were counted daily.…”

Section: Methodsmentioning

confidence: 99%

Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3′-5′)-cyclic-GMP in virulence

Kulesekara¹,

Lee²,

Brencic³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

507

613

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The opportunistic pathogen Pseudomonas aeruginosa is responsible for systemic infections in immunocompromised individuals and chronic respiratory disease in patients with cystic fibrosis. Cyclic nucleotides are known to play a variety of roles in the regulation of virulence-related factors in pathogenic bacteria. A set of P. aeruginosa genes, encoding proteins that contain putative domains characteristic of diguanylate cyclases (DGCs) and phosphodiesterases (PDEs) that are responsible for the maintenance of cellular levels of the second messenger bis-(3′-5′)-cyclic dimeric GMP (c-di-GMP) was identified in the annotated genomes of P. aeruginosa strains PAO1 and PA14. Although the majority of these genes are components of the P. aeruginosa core genome, several are located on presumptive horizontally acquired genomic islands. A comprehensive analysis of P. aeruginosa genes encoding the enzymes of c-di-GMP metabolism (DGC- and PDE-encoding genes) was carried out to analyze the function of c-di-GMP in two disease-related phenomena, cytotoxicity and biofilm formation. Analysis of the phenotypes of DGC and PDE mutants and overexpressing clones revealed that certain virulence-associated traits are controlled by multiple DGCs and PDEs through alterations in c-di-GMP levels. A set of mutants in selected DGC- and PDE-encoding genes exhibited attenuated virulence in a mouse infection model. Given that insertions in different DGC and PDE genes result in distinct phenotypes, it seems likely that the formation or degradation of c-di-GMP by these enzymes is in highly localized and intimately linked to particular targets of c-di-GMP action.

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Section: Methodsmentioning

confidence: 99%

Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3′-5′)-cyclic-GMP in virulence

Kulesekara¹,

Lee²,

Brencic³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

507

613

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“…Thus, the ability of vaccineinduced antibody to protect the cornea against pathology is likely dependent on its ability to transudate onto the cornea along with PMN and complement to promote phagocytic killing of extracellular P. aeruginosa and reduce the overall bacterial numbers. In the burn-wound infection model, mice that are burned and challenged with P. aeruginosa die of systemic infection (12). However, at this time we cannot delineate whether mice immunized with our vaccine were protected at the site of infection or from the dissemination of bacteria.…”

Section: Discussionmentioning

confidence: 97%

“…Hair from the backs of isoflourane-anesthetized immunized NSA-1 mice was clipped followed by the placement of a flame-resistant card against the shaved area. The exposed back was covered with 0.5 ml of ethanol, ignited, and allowed to burn for 10 seconds, as previously described (12,13). This procedure produces a nonlethal 15% total-body surface area third-degree burn.…”

Section: Methodsmentioning

confidence: 99%

Intranasal immunization with heterologously expressed polysaccharide protects against multiple Pseudomonas aeruginosa infections

DiGiandomenico

Rao

Harcher

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Surface-expressed bacterial polysaccharides are often immunodominant, protective antigens. However, these antigens are chemically and serologically highly heterogeneous, and conjugation to protein carriers is often necessary to enhance their immunogenicity. Here we show the efficacy of intranasal immunization of mice with attenuated Salmonella enterica serovar Typhimurium expressing the O antigen portion of Pseudomonas aeruginosa lipopolysaccharide. P. aeruginosa is an ideal model system because it can cause a myriad of localized and systemic infections. In particular, this bacterium is a leading cause of hospital-acquired pneumonia and is responsible for infections after burns and after eye injury. In addition, there are mouse models of infection that mimic the clinical manifestations of P. aeruginosa infections. Immunized mice were highly protected against infection, with long-lasting immunity to acute P. aeruginosa pneumonia, whereas mice immunized with Salmonella containing only the cloning vector or PBS were not. Prophylactic and therapeutic administration of sera from vaccinated animals protected naive mice. Intranasal vaccination also provided complete protection from infections after burns and reduced pathology after corneal abrasions. These results indicate that intranasal delivery of heterologously expressed polysaccharide antigens provides protection at distinct sites of infection. This approach for the expression and delivery of polysaccharide antigens as recombinant immunogens could be easily adapted to develop vaccines for many infectious agents, without the need for complicated purification and conjugation procedures.antibody ͉ Salmonella ͉ vaccine B acterial surface polysaccharides make effective components for vaccines against serious infections because they are generally immunodominant. However, their utility is limited by significant chemical, and hence serologic, variability that requires a large number of components for comprehensive coverage against pathogens capable of expressing different polysaccharide serotypes. Also, purified polysaccharides are often poorly immunogenic, necessitating synthesis of protein-polysaccharide conjugate vaccines. These problems could potentially be overcome by use of recombinant DNA to induce synthesis of the polysaccharides in a heterologous antigen-delivery system. We evaluated this potential by expressing the Pseudomonas aeruginosa LPS O antigen in attenuated Salmonella enterica serovar Typhimurium SL3261 and used this construct to immunize mice intranasally (IN) to evaluate protective immunity against P. aeruginosa infection in the lung and eye, as well as systemic infection emanating from burn wounds.The model polysaccharide that we have used for this study is the P. aeruginosa serogroup O11 O antigen. This serogroup is one of the most prevalent (1) and has been associated with acute infections (2), burns (3), and ulcerative keratitis (4). In addition, P. aeruginosa serogroup O11 strains are among the most pathogenic and lethal because of the expression ...

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“…investigated, a clinical application could be examined. to the one described by Stieritz (54) must be tried and the problems which might arise be overcome. A good review of.burn wounds is found in Nathan (42) and that reference offers a good starting point for future research in burn wounds infected with~· aeruginosa.…”

Section: Gel Filtration Resulted In Approximately Threementioning

confidence: 99%

Purification and properties of lysozyme from Pseudomonas aeruginosa bacteriophage 7v

McFarland¹

2000

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A lysozyme from Bacteriophage 7v was purified 7,7 fold over the original lysates of the bacteriophage 7v and Pseudomonas aeruginosa PS-7· This purification process includes ultracentrifugation, ammonium sulfate precipitation, dialysis, and fractionation in a Sephadex G-150 column. The phage lysozyme exhibits a greater specificity when assayed with P. aeruginosa cells as a substrate, but still is capable of acting on the standard lysozyme Micrococcus lysodeikticus substrate. The pH optimum, heat inactivation range, and action on other bacteria is described. The molecular weight was found to be 14,JOO. The values of this 7v phage lysozyme are in close agreement with values found with other phage lysozymes. A possible treatment for burn wounds infected with Pseudomonas aeruginosa is also described.

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Experimental Studies of the Pathogenesis of Infections Due to Pseudomonas aeruginosa: Description of a Burned Mouse Model

Cited by 257 publications

References 17 publications

Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3′-5′)-cyclic-GMP in virulence

Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3′-5′)-cyclic-GMP in virulence

Intranasal immunization with heterologously expressed polysaccharide protects against multiple Pseudomonas aeruginosa infections

Purification and properties of lysozyme from Pseudomonas aeruginosa bacteriophage 7v

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