From genotype to phenotype: adaptations of Pseudomonas aeruginosa to the cystic fibrosis environment

Camus, Laura; Vandenesch, François; Moreau, Karen

doi:10.1099/mgen.0.000513

Cited by 42 publications

(46 citation statements)

References 169 publications

(536 reference statements)

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“…Changes in the CF gut environment are likely to affect not only which microbes are present but also the metabolic potential and genomic content of the microbes that do thrive. Genetic and metabolic adaptation of opportunistic pathogens to the CF lung environment has been extensively documented ( 171 – 173 ), but very few studies have examined such features in the CF gut. One study demonstrated that E. coli from the CF gut have adapted to the high fat environment, as evidenced by increased growth rate and reduced stress response with glycerol as a sole carbon source ( 174 ).…”

Section: Moving Forwardmentioning

confidence: 99%

The Gut-Lung Axis in Cystic Fibrosis

Price

O’Toole

2021

J Bacteriol

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Cystic Fibrosis (CF) is a heritable, multi-organ disease that impacts all tissues that normally express CFTR protein. While importance of the airway microbiota has long been recognized, the intestinal microbiota has only recently been recognized as an important player in both intestinal and lung health outcomes for persons with CF (pwCF). Here, we summarize current literature related to the gut-lung axis in CF, with a particular focus on three key ideas: Mechanisms through which microbes influence the gut-lung axis, drivers of microbiota alterations, and the potential for intestinal microbiota remediation.

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Section: Moving Forwardmentioning

confidence: 99%

The Gut-Lung Axis in Cystic Fibrosis

Price

O’Toole

2021

J Bacteriol

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“…The loci associated with alarmone ( spoT ), LPS ( pagL ) or alginate biosynthesis ( algG , algU ) and the master regulator gacA exhibited at least twofold higher d N / d S values in the collection of isolates from CF lungs than in those from other habitats. These loci are known to be key for P. aeruginosa to establish its lifestyle in CF airways [ 11 ].…”

Section: Resultsmentioning

confidence: 99%

Sequence diversity of the Pseudomonas aeruginosa population in loci that undergo microevolution in cystic fibrosis airways

Fischer

Klockgether

Sorribes

et al. 2021

Access Microbiology

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Five hundred and thirty-four unrelated Pseudomonas aeruginosa isolates from inanimate habitats, patients with cystic fibrosis (CF) and other human infections were sequenced in 19 genes that had been identified previously as the hot spots of genomic within-host evolution in serial isolates from 12 CF lungs. Amplicon sequencing confirmed a significantly higher sequence diversity of the 19 loci in P. aeruginosa isolates from CF patients compared to those from other habitats, but this overrepresentation was mainly due to the larger share of synonymous substitutions. Correspondingly, non-synonymous substitutions were either rare (gltT, lepA, ptsP) or benign (nuoL, fleR, pelF) in some loci. Other loci, however, showed an accumulation of non-neutral coding variants. Strains from the CF habitat were often mutated at evolutionarily conserved positions in the elements of stringent response (RelA, SpoT), LPS (PagL), polyamine transport (SpuE, SpuF) and alginate biosynthesis (AlgG, AlgU). The strongest skew towards the CF lung habitat was seen for amino acid sequence variants in AlgG that clustered in the carbohydrate-binding/sugar hydrolysis domain. The master regulators of quorum sensing lasR and rhlR were frequent targets for coding variants in isolates from chronic and acute human infections. Unique variants in lasR showed strong evidence of positive selection indicated by d N/d S values of ~4. The pelA gene that encodes a multidomain enzyme involved in both the formation and dispersion of Pel biofilms carried the highest number of single-nucleotide variants among the 19 genes and was the only gene with a higher frequency of missense mutations in P. aeruginosa strains from non-CF habitats than in isolates from CF airways. PelA protein variants are widely distributed in the P. aeruginosa population. In conclusion, coding variants in a subset of the examined loci are indeed characteristic for the adaptation of P. aeruginosa to the CF airways, but for other loci the elevated mutation rate is more indicative of infections in human habitats (lasR, rhlR) or global diversifying selection (pelA).

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“…P. aeruginosa senses S. aureus secreted products and upregulates metal-and metaboliterelated pathways. We focused on the response of P. aeruginosa to S. aureus cell-free supernatant, as opposed to a co-culture model, since P. aeruginosa produces antimicrobials that may kill and lyse S. aureus cells (29,42,43), thus affecting the relative levels of staphylococcal secreted products that may be present. To determine the response of P. aeruginosa PA14 to S. aureus JE2, we performed RNA-seq on early-log phase P. aeruginosa cultures at 20 min, 1 h, and 2 h after the addition of 25% (v/v) S. aureus spent media or the same volume of media as a control.…”

Section: Resultsmentioning

confidence: 99%

Systematic identification of molecular mediators underlying sensing ofStaphylococcus aureusbyPseudomonas aeruginosa

Zarrella

Khare

2021

Preprint

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Bacteria typically exist in dynamic, multispecies communities where polymicrobial interactions influence fitness. Elucidating the molecular mechanisms underlying these interactions is critical for understanding and modulating bacterial behavior in natural environments. While bacterial responses to foreign species are frequently characterized at the molecular and phenotypic level, the exogenous molecules that elicit these responses are understudied. Here we outline a systematic strategy based on transcriptomics combined with genetic and biochemical screens of promoter-reporters to identify the molecules from one species that are sensed by another. We utilized this method to study interactions between the pathogens Pseudomonas aeruginosa and Staphylococcus aureus that are frequently found in co-infections. We discovered that P. aeruginosa senses diverse staphylococcal exoproducts including the metallophore staphylopine, intermediate metabolites citrate and acetoin, and multiple molecules that modulate its iron starvation response. Further, we show that staphylopine inhibits biofilm formation and that P. aeruginosa can utilize citrate and acetoin for growth, revealing that these interactions have both antagonistic and beneficial effects. Our screening approach thus identified multiple S. aureus secreted molecules that are sensed by P. aeruginosa and affect its physiology, demonstrating the efficacy of this approach, and yielding new insight into the molecular basis of interactions between these two species.

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From genotype to phenotype: adaptations of Pseudomonas aeruginosa to the cystic fibrosis environment

Cited by 42 publications

References 169 publications

The Gut-Lung Axis in Cystic Fibrosis

The Gut-Lung Axis in Cystic Fibrosis

Sequence diversity of the Pseudomonas aeruginosa population in loci that undergo microevolution in cystic fibrosis airways

Systematic identification of molecular mediators underlying sensing ofStaphylococcus aureusbyPseudomonas aeruginosa

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