Dataset Information

The influence of human respiratory epithelia on Pseudomonas aeruginosa gene expression.

ABSTRACT: The opportunistic pathogen Pseudomonas aeruginosa can cause acute or chronic infections in humans. Little is known about the initial adaptation of P. aeruginosa to host tissues and the factors that determine whether a P. aeruginosa-epithelial cell interaction will manifest as an acute or a chronic infection. To gain insights into the initial phases of P. aeruginosa infections and to identify P. aeruginosa genes regulated in response to respiratory epithelia, we exposed P. aeruginosa to cultured primary differentiated human airway epithelia. We used a P. aeruginosa strain that causes acute damage to the epithelia and a mutant with defects in Type III secretion and in rhamnolipid synthesis. The mutant did not cause rapid damage to epithelia as did the wildtype. We compared the transcriptomes of the P. aeruginosa wildtype and the mutant to each other and to P. aeruginosa grown under other conditions, and we discovered overlapping sets of differentially expressed genes in the wildtype and mutant exposed to epithelia. A recent study reported that exposure of P. aeruginosa to epithelia is characterized by a repression of the bacterial iron-responsive genes. These findings were suggestive of ample iron availability during infection. In contrast, we found that P. aeruginosa shows an iron-starvation response upon exposure to epithelial cells. This observation highlights the importance of the iron starvation response in both acute and chronic infections and suggests opportunities for therapy.

SUBMITTER: Chugani S

PROVIDER: S-EPMC1934408 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature

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The influence of human respiratory epithelia on Pseudomonas aeruginosa gene expression.

Chugani Sudha S Greenberg E P EP

Microbial pathogenesis 20061212 1

The opportunistic pathogen Pseudomonas aeruginosa can cause acute or chronic infections in humans. Little is known about the initial adaptation of P. aeruginosa to host tissues and the factors that determine whether a P. aeruginosa-epithelial cell interaction will manifest as an acute or a chronic infection. To gain insights into the initial phases of P. aeruginosa infections and to identify P. aeruginosa genes regulated in response to respiratory epithelia, we exposed P. aeruginosa to cultured ...[more]

PMID: 17166692

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Project description:BackgroundThe bacterium Pseudomonas aeruginosa is capable of three types of motilities: swimming, twitching and swarming. The latter is characterized by a fast and coordinated group movement over a semi-solid surface resulting from intercellular interactions and morphological differentiation. A striking feature of swarming motility is the complex fractal-like patterns displayed by migrating bacteria while they move away from their inoculation point. This type of group behaviour is still poorly understood and its characterization provides important information on bacterial structured communities such as biofilms. Using GeneChip® Affymetrix microarrays, we obtained the transcriptomic profiles of both bacterial populations located at the tip of migrating tendrils and swarm center of swarming colonies and compared these profiles to that of a bacterial control population grown on the same media but solidified to not allow swarming motility.ResultsMicroarray raw data were corrected for background noise with the RMA algorithm and quantile normalized. Differentially expressed genes between the three conditions were selected using a threshold of 1.5 log2-fold, which gave a total of 378 selected genes (6.3% of the predicted open reading frames of strain PA14). Major shifts in gene expression patterns are observed in each growth conditions, highlighting the presence of distinct bacterial subpopulations within a swarming colony (tendril tips vs. swarm center). Unexpectedly, microarrays expression data reveal that a minority of genes are up-regulated in tendril tip populations. Among them, we found energy metabolism, ribosomal protein and transport of small molecules related genes. On the other hand, many well-known virulence factors genes were globally repressed in tendril tip cells. Swarm center cells are distinct and appear to be under oxidative and copper stress responses.ConclusionsResults reported in this study show that, as opposed to swarm center cells, tendril tip populations of a swarming colony displays general down-regulation of genes associated with virulence and up-regulation of genes involved in energy metabolism. These results allow us to propose a model where tendril tip cells function as «scouts» whose main purpose is to rapidly spread on uncolonized surfaces while swarm center population are in a state allowing a permanent settlement of the colonized area (biofilm-like).

Project description:UnlabelledAdaptation of bacterial pathogens to a host can lead to the selection and accumulation of specific mutations in their genomes with profound effects on the overall physiology and virulence of the organisms. The opportunistic pathogen Pseudomonas aeruginosa is capable of colonizing the respiratory tract of individuals with cystic fibrosis (CF), where it undergoes evolution to optimize survival as a persistent chronic human colonizer. The transcriptome of a host-adapted, alginate-overproducing isolate from a CF patient was determined following growth of the bacteria in the presence of human respiratory mucus. This stable mucoid strain responded to a number of regulatory inputs from the mucus, resulting in an unexpected repression of alginate production. Mucus in the medium also induced the production of catalases and additional peroxide-detoxifying enzymes and caused reorganization of pathways of energy generation. A specific antibacterial type VI secretion system was also induced in mucus-grown cells. Finally, a group of small regulatory RNAs was identified and a fraction of these were mucus regulated. This report provides a snapshot of responses in a pathogen adapted to a human host through assimilation of regulatory signals from tissues, optimizing its long-term survival potential.ImportanceThe basis for chronic colonization of patients with cystic fibrosis (CF) by the opportunistic pathogen Pseudomonas aeruginosa continues to represent a challenging problem for basic scientists and clinicians. In this study, the host-adapted, alginate-overproducing Pseudomonas aeruginosa 2192 strain was used to assess the changes in its transcript levels following growth in respiratory CF mucus. Several significant and unexpected discoveries were made: (i) although the alginate overproduction in strain 2192 was caused by a stable mutation, a mucus-derived signal caused reduction in the transcript levels of alginate biosynthetic genes; (ii) mucus activated the expression of the type VI secretion system, a mechanism for killing of other bacteria in a mixed population; (iii) expression of a number of genes involved in respiration was altered; and (iv) several small regulatory RNAs were identified, some being mucus regulated. This work highlights the strong influence of the host environment in shaping bacterial survival strategies.

Project description:Thousands of Pseudomonas aeruginosa RNA sequencing (RNA-seq) gene expression profiles are publicly available via the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA). In this work, the transcriptional profiles from hundreds of studies performed by over 75 research groups were reanalyzed in aggregate to create a powerful tool for hypothesis generation and testing. Raw sequence data were uniformly processed using the Salmon pseudoaligner, and this read mapping method was validated by comparison to a direct alignment method. We developed filtering criteria to exclude samples with aberrant levels of housekeeping gene expression or an unexpected number of genes with no reported values and normalized the filtered compendia using the ratio-of-medians method. The filtering and normalization steps greatly improved gene expression correlations for genes within the same operon or regulon across the 2,333 samples. Since the RNA-seq data were generated using diverse strains, we report the effects of mapping samples to noncognate reference genomes by separately analyzing all samples mapped to cDNA reference genomes for strains PAO1 and PA14, two divergent strains that were used to generate most of the samples. Finally, we developed an algorithm to incorporate new data as they are deposited into the SRA. Our processing and quality control methods provide a scalable framework for taking advantage of the troves of biological information hibernating in the depths of microbial gene expression data and yield useful tools for P. aeruginosa RNA-seq data to be leveraged for diverse research goals. IMPORTANCE Pseudomonas aeruginosa is a causative agent of a wide range of infections, including chronic infections associated with cystic fibrosis. These P. aeruginosa infections are difficult to treat and often have negative outcomes. To aid in the study of this problematic pathogen, we mapped, filtered for quality, and normalized thousands of P. aeruginosa RNA-seq gene expression profiles that were publicly available via the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA). The resulting compendia facilitate analyses across experiments, strains, and conditions. Ultimately, the workflow that we present could be applied to analyses of other microbial species.

Dataset Information

The influence of human respiratory epithelia on Pseudomonas aeruginosa gene expression.

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The influence of human respiratory epithelia on Pseudomonas aeruginosa gene expression.

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