The evolution of virulence in Pseudomonas aeruginosa during chronic wound infection
| Autor: | Urvish Trivedi, Jelly Vanderwoude, Derek Fleming, Stephen P. Diggle, Kendra P. Rumbaugh, Sheyda Azimi |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Chronic wound
Evolution Virulence Biology medicine.disease_cause Cystic fibrosis General Biochemistry Genetics and Molecular Biology Microbiology Sepsis Pathogenesis 03 medical and health sciences Mice Antibiotic resistance Serial passage medicine Animals Pseudomonas Infections 030304 developmental biology General Environmental Science 0303 health sciences General Immunology and Microbiology Genetic heterogeneity 030306 microbiology Pseudomonas aeruginosa General Medicine medicine.disease Chronic infection Wound Infection rpoN medicine.symptom General Agricultural and Biological Sciences |
| Zdroj: | Proc Biol Sci Vanderwoude, J, Fleming, D, Azimi, S, Trivedi, U, Rumbaugh, K P & Diggle, S P 2020, ' The evolution of virulence in Pseudomonas aeruginosa during chronic wound infection ', Proceedings of the Royal Society B: Biological Sciences, vol. 287, no. 1937, 20202272 . https://doi.org/10.1098/rspb.2020.2272 |
| Popis: | Opportunistic pathogens are associated with several widespread, recalcitrant chronic infections in humans. As the pipeline for new antibiotics thins, virulence management presents an alternative solution to the rising antimicrobial resistance crisis in treating chronic infections. However, the nature of virulence in opportunists is not fully understood. The trade-off hypothesis has been a popular rationalization for the evolution of parasitic virulence since it was first proposed in the early 1980s, but whether it accurately models the evolutionary trajectories of opportunistic pathogens is still uncertain. Here, we tested the evolution of virulence in the human opportunist Pseudomonas aeruginosa PA14 in a murine chronic wound model. We found that in a serial passage experiment where transmission potential is no longer an epidemiological restriction, virulence does not necessarily increase as is predicted by the trade-off hypothesis, and in fact may evolve in different directions. We also assessed P. aeruginosa adaptations to a chronic wound after ten rounds of selection, and found that phenotypic heterogeneity in P. aeruginosa is limited in chronic wounds compared to heterogeneity seen in cystic fibrosis (CF) infections. Using whole genome sequencing, we found that genes coding for virulence factors thought to be crucial in P. aeruginosa pathogenesis acquired mutations during adaptation in chronic wounds. Our findings highlight that (i) current virulence models do not adequately explain the diverging evolutionary trajectories observed during P. aeruginosa chronic wound infection, (ii) P. aeruginosa phenotypic heterogeneity is less extensive in chronic wounds than in CF lungs, (iii) genes involved in P. aeruginosa virulence acquire mutations in chronic wounds, and (iv) similar adaptations are employed by P. aeruginosa both in a chronic wound and CF lung. |
| Databáze: | OpenAIRE |
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