Dataset Information

Cystic Fibrosis-Associated Stenotrophomonas maltophilia Strain-Specific Adaptations and Responses to pH.

ABSTRACT: The airway fluids of cystic fibrosis (CF) patients contain local pH gradients and are more acidic than those of healthy individuals. pH is a critical factor that is often overlooked in studies seeking to recapitulate the infection microenvironment. We sought to determine the impact of pH on the physiology of a ubiqituous yet understudied microbe, Stenotrophomonas maltophilia Phylogenomics was first used to reconstruct evolutionary relationships between 74 strains of S. maltophilia (59 from CF patients). Neither the core genome (2,158 genes) nor the accessory genome (11,978 genes) distinguish the CF and non-CF isolates; however, strains from similar isolation sources grouped into the same subclades. We grew two human and six CF S. maltophilia isolates from different subclades at a range of pH values and observed impaired growth and altered antibiotic tolerances at pH 5. Transcriptomes revealed increased expression of both antibiotic resistance and DNA repair genes in acidic conditions. Although the gene expression profiles of S. maltophilia in lab cultures and CF sputum were distinct, we found that the same genes associated with low pH were also expressed during infection, and the higher pH cultures were more similar to sputum metatranscriptomes. Our findings suggest that S. maltophilia is not well adapted to acidity and may cope with low pH by expressing stress response genes and colonizing less acidic microenvironments. As a whole, our study underlines the impact of microenvironments on bacterial colonization and adaptation in CF infections.IMPORTANCE Understanding bacterial responses to physiological conditions is an important priority for combating opportunistic infections. The majority of CF patients succumb to inflammation and necrosis in the airways, arising from chronic infection due to ineffective mucociliary clearance. Steep pH gradients characterize the CF airways but are not often incorporated in standard microbiology culture conditions. Stenotrophomonas maltophilia is a prevalent CF opportunistic pathogen also found in many disparate environments, yet this bacterium's contribution to CF lung damage and its response to changing environmental factors remain largely understudied. Here, we show that pH impacts the physiology and antibiotic susceptibility of S. maltophilia, with implications for the development of relevant in vitro models and assessment of antibiotic sensitivity.

SUBMITTER: Gallagher T

PROVIDER: S-EPMC6416904 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Cystic Fibrosis-Associated Stenotrophomonas maltophilia Strain-Specific Adaptations and Responses to pH.

Gallagher Tara T Phan Joann J Oliver Andrew A Chase Alexander B AB England Whitney E WE Wandro Stephen S Hendrickson Clark C Riedel Stefan F SF Whiteson Katrine K

Journal of bacteriology 20190313 7

The airway fluids of cystic fibrosis (CF) patients contain local pH gradients and are more acidic than those of healthy individuals. pH is a critical factor that is often overlooked in studies seeking to recapitulate the infection microenvironment. We sought to determine the impact of pH on the physiology of a ubiqituous yet understudied microbe, <i>Stenotrophomonas maltophilia</i> Phylogenomics was first used to reconstruct evolutionary relationships between 74 strains of <i>S. maltophilia</i> ...[more]

PMID: 30642989

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Project description:Stenotrophomonas maltophilia is a Gram-negative opportunistic pathogen that can infect the lungs of people with cystic fibrosis (CF). The highly viscous mucus in the CF lung, expectorated as sputum, serves as the primary nutrient source for microbes colonizing this site and induces virulence-associated phenotypes and gene expression in several CF pathogens. Here, we characterized the transcriptional responses of three S. maltophilia strains during exposure to synthetic CF sputum medium (SCFM2) to gain insight into how this organism interacts with the host in the CF lung. These efforts led to the identification of 881 transcripts differentially expressed by all three strains, many of which reflect the metabolic pathways used by S. maltophilia in sputum, as well as altered stress responses. The latter correlated with increased resistance to peroxide exposure after pregrowth in SCFM2 for two of the strains. We also compared the SCFM2 transcriptomes of two S. maltophilia CF isolates to that of the acute infection strain, S. maltophilia K279a, allowing us to identify CF isolate-specific signatures in differential gene expression. The expression of genes from the accessory genomes was also differentially altered in response to SCFM2. Finally, a number of biofilm-associated genes were differentially induced in SCFM2, particularly in K279a, which corresponded to increased aggregation and biofilm formation in this strain relative to both CF strains. Collectively, this work details the response of S. maltophilia to an environment that mimics important aspects of the CF lung, identifying potential survival strategies and metabolic pathways used by S. maltophilia during infections.IMPORTANCEStenotrophomonas maltophilia is an important infecting bacterium in the airways of people with cystic fibrosis (CF). However, compared to the other CF pathogens, S. maltophilia has been relatively understudied. The significance of our research is to provide insight into the global transcriptomic changes of S. maltophilia in response to a medium that was designed to mimic important aspects of the CF lung. This study elucidates the overall metabolic changes that occur when S. maltophilia encounters the CF lung and generates a road map of candidate genes to test using in vitro and in vivo models of CF.

Project description:BackgroundStenotrophomonas maltophilia is one of the most common emerging multi-drug resistant organisms found in the lungs of people with cystic fibrosis and its prevalence is increasing. Chronic infection with Stenotrophomonas maltophilia has recently been shown to be an independent predictor of pulmonary exacerbation requiring hospitalization and antibiotics. However, the role of antibiotic treatment of Stenotrophomonas maltophilia infection in people with cystic fibrosis is still unclear. This is an update of a previously published review.ObjectivesThe objective of our review is to assess the effectiveness of antibiotic treatment for Stenotrophomonas maltophilia in people with cystic fibrosis. The primary objective is to assess this in relation to lung function and pulmonary exacerbations in the setting of acute pulmonary exacerbations. The secondary objective is to assess this in relation to the eradication of Stenotrophomonas maltophilia.Search methodsWe searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched a registry of ongoing trials and the reference lists of relevant articles and reviews. Date of latest search: 03 March 2020.Selection criteriaRandomized controlled trials of Stenotrophomonas maltophilia mono-infection or Stenotrophomonas maltophilia co-infection with Pseudomonas aeruginosa in either the setting of an acute pulmonary exacerbation or a chronic infection treated with suppressive antibiotic therapy.Data collection and analysisBoth authors independently assessed the trials identified by the search for potential inclusion in the review.Main resultsWe identified only one trial of antibiotic treatment of pulmonary exacerbations that included people with cystic fibrosis with Stenotrophomonas maltophilia. However, this trial had to be excluded because data was not available per pathogen.Authors' conclusionsThis review did not identify any evidence regarding the effectiveness of antibiotic treatment for Stenotrophomonas maltophilia in people with cystic fibrosis. Until such evidence becomes available, clinicians need to use their clinical judgement as to whether or not to treat Stenotrophomonas maltophilia infection in people with cystic fibrosis. Randomized clinical trials are needed to address these unanswered clinical questions.

Project description:The intrinsic antibiotic resistance of Stenotrophomonas maltophilia, along with its ability to form biofilm both on abiotic surfaces and host tissues, dramatically affects the efficacy of the antibiotic therapy. In this work, 85 S. maltophilia strains isolated in several hospital of central Italy and from several clinical settings were evaluated for their genetic relatedness (by pulsed-field gel electrophoresis, PFGE), biofilm formation (by microtiter plate assay), and planktonic antibiotic resistance (by Kirby-Bauer disk diffusion technique). The S. maltophilia population showed a high genetic heterogeneity: 64 different PFGE types were identified, equally distributed in cystic fibrosis (CF) and non-CF strains, and some consisted of multiple strains. Most of the strains (88.2%) were able to form biofilm, although non-CF strains were significantly more efficient than CF strains. CF strains produced lower biofilm amounts than non-CF strains, both those from respiratory tracts and blood. Non-CF PFGE types 3 and 27 consisted of strong-producers only. Cotrimoxazole and levofloxacin were the most effective antibiotics, being active respectively against 81.2% and 72.9% of strains. CF strains were significantly more resistant to piperacillin/tazobactam compared to non-CF strains (90% versus 53.3%), regardless of sample type. Among respiratory strains, cotrimoxazole was more active against non-CF than CF strains (susceptibility rates: 86.7% versus 75%). The multidrug resistant phenotype was significantly more prevalent in CF than non-CF strains (90% versus 66.7%). Overall, the multidrug-resistance level was negatively associated with efficiency in biofilm formation. Our results showed, for the first time, that in S. maltophilia both classical planktonic drug resistance and the ability of biofilm formation might favor its dissemination in the hospital setting. Biofilm formation might in fact act as a survival mechanism for susceptible bacteria, suggesting that clinical isolates should be routinely assayed for biofilm formation in diagnostic laboratories.

Dataset Information

Cystic Fibrosis-Associated Stenotrophomonas maltophilia Strain-Specific Adaptations and Responses to pH.

Publications

Cystic Fibrosis-Associated Stenotrophomonas maltophilia Strain-Specific Adaptations and Responses to pH.

Similar Datasets

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