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Case Reports
. 2021 Mar 1;203(5):637-640.
doi: 10.1164/rccm.202007-2735LE.

Cystic Fibrosis Lung Function Decline after Within-Host Evolution Increases Virulence of Infecting Pseudomonas aeruginosa

Peter Jorth  1   2 , Samantha Durfey  1 , Amir Rezayat  1 , Jayanthi Garudathri  1 , Anina Ratjen  1 , Benjamin J Staudinger  1 , Matthew C Radey  1 , Alan Genatossio  3 , Sharon McNamara  3 , David A Cook  4 , Moira L Aitken  1 , Ronald L Gibson  1 , Timothy L Yahr  5 , Pradeep K Singh  1
Affiliations
Case Reports

Cystic Fibrosis Lung Function Decline after Within-Host Evolution Increases Virulence of Infecting Pseudomonas aeruginosa

Peter Jorth et al. Am J Respir Crit Care Med. .
No abstract available

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Figures

Figure 1.
Figure 1.
Patient’s lung function decline is associated with mutations in Pseudomonas aeruginosa (Pa) type III secretion (T3S) regulatory genes. Top: Black points represent FEV1 measurements (including stable and exacerbation periods), and blue dotted line indicates segmented linear regression of FEV1 data. ExsD protein diagram indicates the location of the ExsD mutation, and the attached arrow points to the age when it was first detected. The orange horizontal bar on top of FEV1 graph indicates time period when mutant exsDS164P (that hyperactivates T3S) was present, the magenta horizontal bar indicates time period when mutant exsAQ83* (that inactivates T3S) was present, and the inset bar graphs indicate mutant allele frequencies of exsDS164P (orange bars indicate mutant, blue bars indicate wild type) and exsAQ83* (magenta bars indicates mutant, blue bars indicate wild type) as determined by sputum DNA amplicon sequencing. Red arrows indicate the patient’s first two courses of meropenem (Mp) treatment (Mp treatment 1 and Mp treatment 2), and the magenta arrow indicates the when Pa Mp resistance was first reported by the clinical microbiology laboratory. Bottom: Genome map shows genes affected by missense and nonsense mutations, insertions, or deletions present at 100% frequency in the Pa population collected at age 20.4, relative to an isolate collected at age 8.
Figure 2.
Figure 2.
Mutations in type III secretion (T3S) regulatory genes found in patient’s sputum affect T3S. Top: exsA and exsD deletions (ΔexsA and ΔexsD) and the exsDS164P mutation were engineered in the PA103 laboratory strain and T3S toxin secretion was measured by immunoblot, and epithelial cell cytotoxicity was measured by lactate dehydrogenase (LDH) release after 30 minutes. **P < 0.005 and ****P < 0.0001; one-way ANOVA with Dunnet’s correction for multiple comparisons compared with wild type. Bottom: production of T3S toxins (ExoS/T) and the needle protein that inject T3S toxins (PcrV) by Pseudomonas aeruginosa (Pa) with indicated genotypes measured by immunoblot. Isolates were collected from the patient at the onset of lung function decline at age 15.6 (isolates 15.6Ya and b) and during the postdecline stable period at age 20.4 (isolate 20.4Y). WT = wild type.
See this image and copyright information in PMC

References

    1. Burns JL, Gibson RL, McNamara S, Yim D, Emerson J, Rosenfeld M, et al. Longitudinal assessment of Pseudomonas aeruginosa in young children with cystic fibrosis. J Infect Dis. 2001;183:444–452. - PubMed
    1. Williams D, Evans B, Haldenby S, Walshaw MJ, Brockhurst MA, Winstanley C, et al. Divergent, coexisting Pseudomonas aeruginosa lineages in chronic cystic fibrosis lung infections. Am J Respir Crit Care Med. 2015;191:775–785. - PMC - PubMed
    1. Feigelman R, Kahlert CR, Baty F, Rassouli F, Kleiner RL, Kohler P, et al. Sputum DNA sequencing in cystic fibrosis: non-invasive access to the lung microbiome and to pathogen details. Microbiome. 2017;5:20. - PMC - PubMed
    1. Smith EE, Buckley DG, Wu Z, Saenphimmachak C, Hoffman LR, D’Argenio DA, et al. Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc Natl Acad Sci USA. 2006;103:8487–8492. - PMC - PubMed
    1. McCaw ML, Lykken GL, Singh PK, Yahr TL. ExsD is a negative regulator of the Pseudomonas aeruginosa type III secretion regulon. Mol Microbiol. 2002;46:1123–1133. - PubMed

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