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

Pustelny, Christian; Komor, Uliana; Pawar, Vinay; Lorenz, Anne; Bielecka, Agata; Moter, Annette; Gocht, Benjamin; Eckweiler, Denitsa; Müsken, Mathias; Grothe, Claudia; Lünsdorf, Heinrich; Weiß, Siegfried; Häußler, Susanne

doi:10.1128/iai.02234-14

Cited by 47 publications

(36 citation statements)

References 58 publications

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“…The model is also applicable for unraveling the complex interactions that occur during P. aeruginosa coinfections with other bacteriatypically with Staphylococcus aureus or anaerobes (38). Furthermore, it is possible to evaluate the efficacy of classical antimicrobial agents against P. aeruginosa biofilm infections and optimize the combinations and application regimens thereof.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

In Vivo Efficacy of Antimicrobials against Biofilm-Producing Pseudomonas aeruginosa

Pawar

Komor

Kasnitz

et al. 2015

Antimicrob Agents Chemother

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“…Our results are in accord with recently reported associations between these taxa and cancer. Guerrero-Preston et al (2016) demonstrated that Streptococcus Haemophilus and Veillonella were the most abundant taxa in the saliva of OSCC patients, and Pustelny et al (2015) showed that Veillonella parvula preferentially colonizes neoplastic tissues. Higher proportions of Haemophilus and Neisseria have been detected in patients with oral leukoplakia (Hu et al 2016) and oral erosive lichen planus (Wang et al 2016), respectively.…”

Section: Discussionmentioning

confidence: 99%

The Salivary Microbiome and Oral Cancer Risk: A Pilot Study in Fanconi Anemia

et al. 2016

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Fanconi anemia (FA) is a rare genetic disease characterized by chromosomal instability and impaired DNA damage repair. FA patients develop oral squamous cell carcinoma (OSCC) earlier and more frequently than the general population, especially after hematopoietic stem cell transplantation (HSCT). Although evidence of an etiological role of the local microbiome and carcinogenesis has been mounting, no information exists regarding the oral microbiome of FA patients. The aim of this study was to explore the salivary microbiome of 61 FA patients regarding their oral health status and OSCC risk factors. After answering a questionnaire and receiving clinical examination, saliva samples were collected and analyzed using 16S rRNA sequencing of the V3-V4 hypervariable region. The microbial profiles associated with medical and clinical parameters were analyzed using general linear models. Patients were young (mean age, 22 y) and most had received HSCT (n = 53). The most abundant phyla were Firmicutes [mean relative abundance (SD), 42.1% (10.1%)] and Bacteroidetes [(25.4% (11.4%)]. A history of graft-versus-host disease (GVHD) (n = 27) was associated with higher proportions of Firmicutes (43.8% × 38.5%, P = 0.05). High levels of gingival bleeding were associated with the genera Prevotella (22.25% × 20%), Streptococcus (19.83% × 17.61%), Porphyromonas (3.63% × 1.42%, P = 0.03), Treponema (1.02% × 0.28%, P = 0.009), Parvimonas (0.28% × 0.07%, P = 0.02) and Dialister (0.27% × 0.10%, P = 0.04). Finally, participants transplanted over 11 y ago showed the highest levels of Streptococcus (18.4%), Haemophilus (12.7%) and Neisseria (6.8%). In conclusion, FA patients that showed poor oral hygiene harbored higher proportions of the genera of bacteria compatible with gingival disease. Specific microbial differences were associated with a history of oral GVHD and a history of oral mucositis.

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“…Contrary to this, Prevotella intermedia was shown to induce a humoral immune response in PWCF and to mediate an influx of neutrophils and macrophages, thereby increasing CF airway inflammation (12). Furthermore, anaerobes belonging to the oropharyngeal flora have been shown to enhance the virulence of P. aeruginosa in a number of infection models (13)(14)(15)(16)(17).…”

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confidence: 99%

The Role of Short-Chain Fatty Acids, Produced by Anaerobic Bacteria, in the Cystic Fibrosis Airway

Mirković

Murray

Lavelle

et al. 2015

Am J Respir Crit Care Med

110

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Rationale: Anaerobic bacteria are present in large numbers in the airways of people with cystic fibrosis (PWCF). In the gut, anaerobes produce short-chain fatty acids (SCFAs) that modulate immune and inflammatory processes.Objectives: To investigate the capacity of anaerobes to contribute to cystic fibrosis (CF) airway pathogenesis via SCFAs.Methods: Samples of 109 PWCF were processed using anaerobic microbiological culture with bacteria present identified by 16S RNA sequencing. SCFA levels in anaerobic supernatants and bronchoalveolar lavage (BAL) were determined by gas chromatography. The mRNA and/or protein expression of two SCFA receptors, GPR41 and GPR43, in CF and non-CF bronchial brushings and 16HBE14o 2 and CFBE41o 2 cells were evaluated using reverse transcription polymerase chain reaction, Western blot analysis, laser scanning cytometry, and confocal microscopy. SCFA-induced IL-8 secretion was monitored by ELISA.Measurements and Main Results: Fifty-seven (52.3%) of 109 PWCF were anaerobe positive. Prevalence increased with age, from 33.3% to 57.7% in PWCF younger (n = 24) and older (n = 85) than 6 years of age. All evaluated anaerobes produced millimolar concentrations of SCFAs, including acetic, propionic, and butyric acids. SCFA levels were higher in BAL samples of adults than in those of children. GPR41 levels were elevated in CFBE41o 2 versus 16HBE14o 2 cells; CF versus non-CF bronchial brushings; and 16HBE14o 2 cells after treatment with cystic fibrosis transmembrane conductance regulator inhibitor CFTR(inh)-172, CF BAL, or inducers of endoplasmic reticulum stress. SCFAs induced a dosedependent and pertussis toxin-sensitive IL-8 response in bronchial epithelial cells, with a higher production of IL-8 in CFBE41o 2 than in 16HBE14o 2 cells.Conclusions: This study illustrates that SCFAs contribute to excessive production of IL-8 in CF airways colonized with anaerobes via up-regulated GPR41.Keywords: anaerobic bacteria; cystic fibrosis; inflammation; short-chain fatty acids Correspondence and requests for reprints should be addressed to Bojana Mirković, Ph

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

Cited by 47 publications

References 58 publications

In Vivo Efficacy of Antimicrobials against Biofilm-Producing Pseudomonas aeruginosa

In Vivo Efficacy of Antimicrobials against Biofilm-Producing Pseudomonas aeruginosa

The Salivary Microbiome and Oral Cancer Risk: A Pilot Study in Fanconi Anemia

The Role of Short-Chain Fatty Acids, Produced by Anaerobic Bacteria, in the Cystic Fibrosis Airway

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