Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

Tyrrell, Jean; Callaghan, Máire

doi:10.1099/mic.0.000220

Cited by 45 publications

(36 citation statements)

References 210 publications

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“…To match conditions where the competitive exclusion principle applies (Hardin, 1960), we created an environment where the two species compete for a single limiting resourceiron: a key essential nutrient, limiting bacterial growth both in natural environments (Hersman et al, 2000) and within hosts (Miethke and Marahiel, 2007). In order to scavenge iron, both species rely on the secretion of small peptide derivates (pyoverdine for PA and ornibactin for BC), called siderophores (Miethke and Marahiel, 2007;Tyrrell and Callaghan, 2015). Importantly, pyoverdine production in PA is a cooperative trait as secreted molecules can be shared as public goods within the Pseudomonas population (Griffin et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Cheating fosters species co-existence in well-mixed bacterial communities

2017

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Explaining the enormous biodiversity observed in bacterial communities is challenging because ecological theory predicts that competition between species occupying the same niche should lead to the exclusion of less competitive community members. Competitive exclusion should be particularly strong when species compete for a single limiting resource or live in unstructured habitats that offer no refuge for weaker competitors. Here, we describe the 'cheating effect', a form of intra-specific competition that can counterbalance between-species competition, thereby fostering biodiversity in unstructured habitats. Using experimental communities consisting of the strong competitor Pseudomonas aeruginosa (PA) and its weaker counterpart Burkholderia cenocepacia (BC), we show that co-existence is impossible when the two species compete for a single limiting resource, iron. However, when introducing a PA cheating mutant, which specifically exploits the iron-scavenging siderophores produced by the PA wild type, we found that biodiversity was preserved under well-mixed conditions where PA cheats could outcompete the PA wild type. Cheating fosters biodiversity in our system because it creates strong intra-specific competition, which equalizes fitness differences between PA and BC. Our study identifies cheating - typically considered a destructive element - as a constructive force in shaping biodiversity.

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Section: Introductionmentioning

confidence: 99%

Cheating fosters species co-existence in well-mixed bacterial communities

2017

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“…increased mucus volume and adhesivity in CF. The chemical environment also differs as different substrates for growth become available: in CF, bacteria use amino acids released by damaged tissues, or from mucus, as carbon sources and do not experience the iron restriction characteristic of healthy tissue (Tyrrell & Callaghan, 2016). Consequently, gene expression and the roles played by virulence factors differ in chronic versus acute contexts (Palmer et al, 2005;LaFayette et al, 2015;Turner et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

An ex vivo lung model to study bronchioles infected with Pseudomonas aeruginosa biofilms

Harrison

Diggle

2016

Microbiology

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A key aim in microbiology is to determine the genetic and phenotypic bases of bacterial virulence, persistence and antimicrobial resistance in chronic biofilm infections. This requires tractable, high-throughput models that reflect the physical and chemical environment encountered in specific infection contexts. Such models will increase the predictive power of microbiological experiments and provide platforms for enhanced testing of novel antibacterial or antivirulence therapies. We present an optimized ex vivo model of cystic fibrosis lung infection: ex vivo culture of pig bronchiolar tissue in artificial cystic fibrosis mucus. We focus on the formation of biofilms by Pseudomonas aeruginosa. We show highly repeatable and specific formation of biofilms that resemble clinical biofilms by a commonly studied laboratory strain and ten cystic fibrosis isolates of this key opportunistic pathogen.

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“…; Miethke and Marahiel ). To overcome iron limitation, bacteria secrete siderophores, small secondary metabolites, which make ferric iron bio‐available for all individuals with a specific receptor for uptake (Ratledge and Dover ; Miethke and Marahiel ; Tyrrell and Callaghan ). Previous research showed that siderophores play a crucial role for both intra‐ and interspecific competition (Griffin et al.…”

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confidence: 99%

The bacteriumPseudomonas aeruginosasenses and gradually responds to interspecific competition for iron

2018

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Phenotypic plasticity in response to competition is a well-described phenomenon in higher organisms. Here, we show that also bacteria have the ability to sense the presence of competitors and mount fine-tuned responses to match prevailing levels of competition. In our experiments, we studied interspecific competition for iron between the bacterium Pseudomonas aeruginosa (PA) and its competitor Burkholderia cenocepacia (BC). We focused on the ability of PA to phenotypically adjust the production of pyoverdine, an iron-scavenging siderophore. We found that PA upregulates pyoverdine production early on during competition under condition of low iron availability. This plastic upregulation was fine-tuned in response to the level of competition imposed by BC, and seems to confer a relative fitness benefit to PA in the form of an earlier initiation of growth. At later time points, however, PA showed reduced growth in mixed compared to monoculture, suggesting that competitive responses are costly. Altogether, our results demonstrate that phenotypic plasticity in siderophore production plays an important role in interspecific competition for iron. Upregulating siderophore production may be a powerful strategy to lock iron away from competing species, and to reserve this nutrient for strain members possessing the compatible receptor for uptake.

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Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

Cited by 45 publications

References 210 publications

Cheating fosters species co-existence in well-mixed bacterial communities

Cheating fosters species co-existence in well-mixed bacterial communities

An ex vivo lung model to study bronchioles infected with Pseudomonas aeruginosa biofilms

The bacteriumPseudomonas aeruginosasenses and gradually responds to interspecific competition for iron

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