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Replication of the Ordered, Nonredundant Library of Pseudomonas aeruginosa strain PA14 Transposon Insertion Mutants
Published on: May 4, 2018
High frequency body site translocation of nosocomial Pseudomonas aeruginosa
Lewis W S Fisher1, Harry A Thorpe2, Davide Sassera3,4
1Parasites and Microbes, Wellcome Sanger Institute, Cambridge, UK.
Abstract:
Pseudomonas aeruginosa is an important nosocomial pathogen which can cause serious infections across diverse anatomic locations. Infections can spread within an individual to different body sites, but the rate and directionality of this process is unknown. Here, we explore within-host diversity as well as the body site translocation dynamics using de-convoluted metagenomic P. aeruginosa reads from 256 hospital patients sampled at both respiratory and gut sites. Of the 84 patients where P. aeruginosa genomes could be recovered, there were 27 cases where the same P. aeruginosa clone was detected across multiple body sites. Using a simulation approach, we find that the majority of body site sharing is likely due to within-patient translocation of clones rather than independent acquisition from the hospital environment. Using ancestral reconstruction, we predict that most clones likely occupied a respiratory niche, and that the probable direction of clone transmission is lung-to-gut. Analysis of within-patient variation highlights strong enrichment of mutations in genes associated with antimicrobial resistance, irrespective of sample type. We report significantly more translocation than has been previously reported and highlight that lower respiratory tract infections can result in persistent gut colonisation of P. aeruginosa, a major risk factor for sepsis in vulnerable patients.
Insights
Pseudomonas aeruginosa infections spread within patients, primarily from the lungs to the gut. This translocation, not hospital acquisition, explains clone sharing and drives antimicrobial resistance.
Area of Science:
- Microbiology
- Genomics
- Infectious Diseases
Background:
- Pseudomonas aeruginosa is a significant nosocomial pathogen causing diverse infections.
- Understanding within-host spread and body site translocation is crucial for infection control.
Purpose of the Study:
- To investigate the dynamics of Pseudomonas aeruginosa body site translocation within individual patients.
- To determine the primary source of P. aeruginosa clone sharing across different body sites.
Main Methods:
- Analysis of de-convoluted metagenomic P. aeruginosa reads from respiratory and gut samples of 256 hospital patients.
- Genomic recovery from 84 patients, identifying shared clones across body sites.
- Simulation and ancestral reconstruction to infer translocation directionality and origins.
Main Results:
- Identified 27 cases with the same P. aeruginosa clone across multiple body sites.
- Simulation results indicate within-patient translocation is the main driver of clone sharing, not environmental acquisition.
- Ancestral reconstruction suggests a lung-to-gut transmission direction for most clones.
- Observed significant enrichment of antimicrobial resistance mutations within patients.
Conclusions:
- Lower respiratory tract infections with P. aeruginosa can lead to persistent gut colonization.
- This lung-to-gut translocation is a significant factor in P. aeruginosa spread within hospitals.
- Findings highlight the importance of understanding within-host dynamics for managing P. aeruginosa infections and sepsis risk.
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