Biofilm formation by Pseudomonas aeruginosa in solid murine tumors – a novel model system

Komor, Uliana; Bielecki, Piotr; Loessner, Holger; Rohde, Manfred; Wolf, Kathrin; Westphal, Kathrin; Weiß, Siegfried; Häußler, Susanne

doi:10.1016/j.micinf.2012.04.002

Cited by 34 publications

(40 citation statements)

References 34 publications

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“…Furthermore, histology revealed a strong inflammatory response and attraction of neutrophils in the colonized tumors ( Fig. 1e and f) (20).…”

Section: Resultsmentioning

confidence: 94%

“…In previous publications, we could show that P. aeruginosa is able to efficiently colonize solid murine tumors and to form biofilm-like structures in such tissue (20,21). Here, we aimed at calibrating the model system to evaluate the effectiveness of antimicrobial compounds and antimicrobial combinations against biofilm-grown bacteria in vivo.…”

Section: Resultsmentioning

confidence: 99%

“…It employs transplantable solid tumors in mice that are preferentially colonized by P. aeruginosa as well as by other bacteria after systemic administration (18). The microenvironment of the colonized tumor leads to biofilm formation by the bacteria (18)(19)(20). Apparently, this microenvironment of the murine tumor resembles very closely that found in the CF lung or in burn wounds (21).…”

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confidence: 99%

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In Vivo Efficacy of Antimicrobials against Biofilm-Producing Pseudomonas aeruginosa

Pawar

Komor

Kasnitz

et al. 2015

Antimicrob Agents Chemother

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e Patients suffering from cystic fibrosis (CF) are commonly affected by chronic Pseudomonas aeruginosa biofilm infections. This is the main cause for the high disease severity. In this study, we demonstrate that P. aeruginosa is able to efficiently colonize murine solid tumors after intravenous injection and to form biofilms in this tissue. Biofilm formation was evident by electron microscopy. Such structures could not be observed with transposon mutants, which were defective in biofilm formation. Comparative transcriptional profiling of P. aeruginosa indicated physiological similarity of the bacteria in the murine tumor model and the CF lung. The efficacy of currently available antibiotics for treatment of P. aeruginosa-infected CF lungs, such as ciprofloxacin, colistin, and tobramycin, could be tested in the tumor model. We found that clinically recommended doses of these antibiotics were unable to eliminate wild-type P. aeruginosa PA14 while being effective against biofilm-defective mutants. However, colistin-tobramycin combination therapy significantly reduced the number of P. aeruginosa PA14 cells in tumors at lower concentrations. Hence, we present a versatile experimental system that is providing a platform to test approved and newly developed antibiofilm compounds.

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“…Furthermore, histology revealed a strong inflammatory response and attraction of neutrophils in the colonized tumors ( Fig. 1e and f) (20).…”

Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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In Vivo Efficacy of Antimicrobials against Biofilm-Producing Pseudomonas aeruginosa

Pawar

Komor

Kasnitz

et al. 2015

Antimicrob Agents Chemother

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“…It has previously been shown that facultative anaerobic bacteria, such as Salmonella Typhimurium and Escherichia coli, are able to colonize solid subcutaneous tumors of the colon carcinoma cell line CT26 in a mouse tumor model (50). We have further demonstrated that P. aeruginosa, although rapidly cleared from the blood and other organs, is also able to gather and multiply specifically in the murine tumor tissue following intravenous administration (31,32). Of note, whereas facultative anaerobic bacteria like Salmonella colonize the whole tumor tissue, including the anaerobic center, the nonfermenter P. aeruginosa colonized mainly the outer rim of the tumor tissue.…”

Section: Resultsmentioning

confidence: 64%

“…We addressed the question of whether and how cocultures of V. parvula and P. aeruginosa influence each other. In addition to in vitro studies, such as growth competition experiments, transcriptional profiling, and analyses on biofilm formation, we used our recently established in vivo murine tumor model (31). In this model, we inject CT26 tumor cells into syngeneic BALB/c mice subcutaneously, and when the tumor has reached a certain size, bacteria are administered intravenously.…”

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confidence: 99%

Contribution of Veillonella parvula to Pseudomonas aeruginosa-Mediated Pathogenicity in a Murine Tumor Model System

et al. 2015

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fThe recent finding that high numbers of strict anaerobes are present in the respiratory tract of cystic fibrosis (CF) patients has drawn attention to the pathogenic contribution of the CF microbiome to airway disease. In this study, we investigated the specific interactions of the most dominant bacterial CF pathogen, Pseudomonas aeruginosa, with the anaerobic bacterium Veillonella parvula, which has been recovered at comparable cell numbers from the respiratory tract of CF patients. In addition to growth competition experiments, transcriptional profiling, and analyses of biofilm formation by in vitro studies, we used our recently established in vivo murine tumor model to investigate mutual influences of the two pathogens during a biofilm-associated infection process. We found that P. aeruginosa and V. parvula colonized distinct niches within the tumor. Interestingly, significantly higher cell numbers of P. aeruginosa could be recovered from the tumor tissue when mice were coinfected with both bacterial species than when mice were monoinfected with P. aeruginosa. Concordantly, the results of in vivo transcriptional profiling implied that the presence of V. parvula supports P. aeruginosa growth at the site of infection in the host, and the higher P. aeruginosa load correlated with clinical deterioration of the host. Although many challenges must be overcome to dissect the specific interactions of coinfecting bacteria during an infection process, our findings exemplarily demonstrate that the complex interrelations between coinfecting microorganisms and the immune responses determine clinical outcome to a much greater extent than previously anticipated.

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Insights into host–pathogen interactions from state‐of‐the‐art animal models of respiratory Pseudomonas aeruginosa infections

et al. 2016

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Pseudomonas aeruginosa is an important opportunistic pathogen that can cause acute respiratory infections in immunocompetent patients or chronic infections in immunocompromised individuals and in patients with cystic fibrosis. When acquiring the chronic infection state, bacteria are encapsulated within biofilm structures enabling them to withstand diverse environmental assaults, including immune reactions and antimicrobial therapy. Understanding the molecular interactions within the bacteria, as well as with the host or other bacteria, is essential for developing innovative treatment strategies. Such knowledge might be accumulated in vitro. However, it is ultimately necessary to confirm these findings in vivo. In the present Review, we describe state‐of‐the‐art in vivo models that allow studying P. aeruginosa infections in molecular detail. The portrayed mammalian models exclusively focus on respiratory infections. The data obtained by alternative animal models which lack lung tissue, often provide molecular insights that are easily transferable to mammals. Importantly, these surrogate in vivo systems reveal complex molecular interactions of P. aeruginosa with the host. Herein, we also provide a critical assessment of the advantages and disadvantages of such models.

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Biofilm formation by Pseudomonas aeruginosa in solid murine tumors – a novel model system

Cited by 34 publications

References 34 publications

In Vivo Efficacy of Antimicrobials against Biofilm-Producing Pseudomonas aeruginosa

In Vivo Efficacy of Antimicrobials against Biofilm-Producing Pseudomonas aeruginosa

Contribution of Veillonella parvula to Pseudomonas aeruginosa-Mediated Pathogenicity in a Murine Tumor Model System

Insights into host–pathogen interactions from state‐of‐the‐art animal models of respiratory Pseudomonas aeruginosa infections

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