Pseudomonas aeruginosa is the main cause of fatal chronic lung infections among individuals suffering from cystic fibrosis (CF). During the past 15 years, particularly aggressive strains transmitted among CF patients have been identified, initially in Europe and more recently in Canada. The aim of this study was to generate high-quality genome sequences for 7 isolates of the Liverpool epidemic strain (LES) from the United Kingdom and Canada representing different virulence characteristics in order to: (1) associate comparative genomics results with virulence factor variability and (2) identify genomic and/or phenotypic divergence between the two geographical locations. We performed phenotypic characterization of pyoverdine, pyocyanin, motility, biofilm formation, and proteolytic activity. We also assessed the degree of virulence using the Dictyostelium discoideum amoeba model. Comparative genomics analysis revealed at least one large deletion (40–50 kb) in 6 out of the 7 isolates compared to the reference genome of LESB58. These deletions correspond to prophages, which are known to increase the competitiveness of LESB58 in chronic lung infection. We also identified 308 non-synonymous polymorphisms, of which 28 were associated with virulence determinants and 52 with regulatory proteins. At the phenotypic level, isolates showed extensive variability in production of pyocyanin, pyoverdine, proteases and biofilm as well as in swimming motility, while being predominantly avirulent in the amoeba model. Isolates from the two continents were phylogenetically and phenotypically undistinguishable. Most regulatory mutations were isolate-specific and 29% of them were predicted to have high functional impact. Therefore, polymorphism in regulatory genes is likely to be an important basis for phenotypic diversity among LES isolates, which in turn might contribute to this strain’s adaptability to varying conditions in the CF lung.
Background: Mechanisms underlying the success of Pseudomonas aeruginosa in chronic lung infection among cystic fibrosis (CF) patients are poorly defined. The modA gene was previously linked to in vivo competitiveness of P. aeruginosa by a genetic screening in the rat lung. This gene encodes a subunit of transporter ModABC, which is responsible for extracellular uptake of molybdate. This compound is essential for molybdoenzymes, including nitrate reductases. Since anaerobic growth conditions are known to occur during CF chronic lung infection, inactivation of a molybdate transporter could inhibit proliferation through the inactivation of denitrification enzymes. Hence, we performed phenotypic characterization of a modA mutant strain obtained by signature-tagged mutagenesis (STM_modA) and assessed its virulence in vivo with two host models. Results:The STM_modA mutant was in fact defective for anaerobic growth and unable to use nitrates in the growth medium for anaerobic respiration. Bacterial growth and nitrate usage were restored when the medium was supplemented with molybdate. Most significantly, the mutant strain showed reduced virulence compared to wild-type strain PAO1 according to a competitive index in the rat model of chronic lung infection and a predation assay with Dictyostelium discoideum amoebae. As the latter took place in aerobic conditions, the in vivo impact of the mutation in modA appears to extend beyond its effect on anaerobic growth. Conclusions:These results support the modABC-encoded transporter as important for the pathogenesis of P. aeruginosa, and suggest that enzymatic machinery implicated in anaerobic growth during chronic lung infection in CF merits further investigation as a potential target for therapeutic intervention.
Pseudomonas aeruginosa displays broad genetic diversity, giving it an astonishing capacity to adapt to a variety of environments and to infect a wide range of hosts. While many P. aeruginosa isolates of various origins have been analyzed, isolates from cystic fibrosis (CF) patients have received the most attention. Less is known about the genetic and phenotypic diversity of P. aeruginosa isolates that colonize other environments where flourishing biofilms can be found. In the present study, 29 P. aeruginosa isolates from dental unit waterlines and CF patients were collected and their genetic and phenotypes profiles were compared to determine whether environmental and clinical isolates are related. The isolates were first classified using the random amplified polymorphic DNA method. This made it possible to distribute the isolates into one clinical cluster and two environmental clusters. The isolates in the environmental cluster that were genetically closer to the clinical cluster also displayed phenotypes similar to the clinical isolates. The isolates from the second environmental cluster displayed opposite phenotypes, particularly an increased capacity to form biofilms. The isolates in this cluster were also the only ones harboring genes that encoded specific epimerases involved in the synthesis of lipopolysaccharides, which could explain their increased ability to form biofilms. In conclusion, the isolates from the dental unit waterlines could be distributed into two clusters, with some of the environmental isolates resembled the clinical isolates.
Research on refugee trajectories rarely takes into account social class. Yet migration options for those fleeing conflicts and insecurity are more or less dangerous, desirable and doable and differences in trajectories have to do with people's ability to mobilise resources at a given time and in a given space. Based on 42 semistructured interviews conducted with Syrians who fled to Lebanon and Turkey between 2012 and 2017, this article focuses on how trajectories of exile are shaped by the interactions between social class and the specificities of the context of reception. These countries are similar to the extent that they both border Syria and host the largest numbers of Syrian refugees worldwide. Yet their respective policies, as well as their unique historical, legal and socio‐economic contexts, create different impacts on refugee trajectories and refugees' experience of inequality. We argue that as a result of the different contexts of reception for Syrians in Lebanon and Turkey, refugees' strategies to reduce precarity also differ significantly. As such, the relevance and usefulness of any given form of capital vary. Results indicate that survival strategies and mobilisation of capital in Lebanon revolve around obtaining legal status, whereas in Turkey, where all Syrian refugees benefit from legal status under the temporary protection regime, capital is mainly used to negotiate an exploitative labour market. Our study challenges conventional class analyses that imply direct links between the possession of economic and social capital and favourable trajectories of exile.
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