<i>Ex vivo</i>transcriptional profiling reveals a common set of genes important for the adaptation of<i><scp>P</scp>seudomonas aeruginosa</i>to chronically infected host sites

Bielecki, Piotr; Komor, Uliana; Bielecka, Agata; Müsken, Mathias; Puchałka, Jacek; Pletz, Mathias W.; Ballmann, Manfred; Santos, Vítor A. P. Martins dos; Weiß, Siegfried; Häußler, Susanne

doi:10.1111/1462-2920.12024

Cited by 42 publications

(47 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Second, the niche within the tumor largely reflects environmental characteristics of the chronically infected CF respiratory tract. The in vivo transcription profile of wild-type P. aeruginosa isolated from tumors was previously shown to match that of isolates from CF lungs and lesions of patients suffering from burn wounds (21). This provides evidence that the microenvironments of colonized solid tumors and CF lungs or burn wounds are very similar.…”

Section: Discussionmentioning

confidence: 56%

“…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).…”

mentioning

confidence: 64%

“…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%

See 2 more Smart Citations

In Vivo Efficacy of Antimicrobials against Biofilm-Producing Pseudomonas aeruginosa

Pawar

Komor

Kasnitz

et al. 2015

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 56%

mentioning

confidence: 64%

See 1 more Smart Citation

In Vivo Efficacy of Antimicrobials against Biofilm-Producing Pseudomonas aeruginosa

Pawar

Komor

Kasnitz

et al. 2015

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

show abstract

“…To our knowledge, this is the first report linking the catabolism of host-derived substrates and increased Anr activity under conditions where Anr is thought to be largely inactive because of the presence of oxygen (17,55). A recent study has shown that P. aeruginosa betI and betB transcripts were particularly upregulated in CF patient lung infections, as well as burn wound samples, compared to those in planktonic controls (56). Because the betaine aldehyde dehydrogenase-encoding genes are responsible for the conversion of choline to GB (57), this implies choline uptake and utilization in vivo.…”

Section: Discussionmentioning

confidence: 70%

Anr and Its Activation by PlcH Activity in Pseudomonas aeruginosa Host Colonization and Virulence

et al. 2013

View full text Add to dashboard Cite

bPseudomonas aeruginosa hemolytic phospholipase C (PlcH) degrades phosphatidylcholine (PC), an abundant lipid in cell membranes and lung surfactant. A ⌬plcHR mutant, known to be defective in virulence in animal models, was less able to colonize epithelial cell monolayers and was defective in biofilm formation on plastic when grown in lung surfactant. Microarray analyses found that strains defective in PlcH production had lower levels of Anr-regulated transcripts than the wild type. PC degradation stimulated the Anr regulon in an Anr-dependent manner under conditions where Anr activity was submaximal because of the presence of oxygen. Two PC catabolites, choline and glycine betaine (GB), were sufficient to stimulate Anr activity, and their catabolism was required for Anr activation. The addition of choline or GB to glucose-containing medium did not alter Anr protein levels, growth rates, or respiratory activity, and Anr activation could not be attributed to the osmoprotectant functions of GB. The ⌬anr mutant was defective in virulence in a mouse pneumonia model. Several lines of evidence indicate that Anr is important for the colonization of biotic and abiotic surfaces in both P. aeruginosa PAO1 and PA14 and that increases in Anr activity resulted in enhanced biofilm formation. Our data suggest that PlcH activity promotes Anr activity in oxic environments and that Anr activity contributes to virulence, even in the acute infection phase, where low oxygen tensions are not expected. This finding highlights the relationships among in vivo bacterial metabolism, the activity of the oxygen-sensitive regulator Anr, and virulence.

show abstract

“…In addition, we could show that Salmonella enterica serovar Typhimurium, as well as P. aeruginosa, forms biofilms in this neoplastic tissue (32). Transcriptional profiling of tumor-colonizing P. aeruginosa revealed that the microenvironment encountered by the bacteria in the tumor closely resembles the microenvironment of the CF lung (33). Using this model, we set out to investigate species-dependent phenotypic and transcriptomic changes during in vivo coinfections by V. parvula and P. aeruginosa.…”

mentioning

confidence: 99%

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

et al. 2015

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Ex vivotranscriptional profiling reveals a common set of genes important for the adaptation ofPseudomonas aeruginosato chronically infected host sites

Cited by 42 publications

References 57 publications

In Vivo Efficacy of Antimicrobials against Biofilm-Producing Pseudomonas aeruginosa

In Vivo Efficacy of Antimicrobials against Biofilm-Producing Pseudomonas aeruginosa

Anr and Its Activation by PlcH Activity in Pseudomonas aeruginosa Host Colonization and Virulence

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

Contact Info

Product

Resources

About