Genomic virulence markers are associated with severe outcomes in patients with Pseudomonas aeruginosa bloodstream infection
Abstract Background Pseudomonas aeruginosa (PA) bloodstream infection (BSI) is a common healthcare-associated complication linked to antimicrobial resistance and high mortality. Ongoing clinical trials are exploring novel anti-virulence agents, yet studies on how bacterial virulence affects PA infec...
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Nature Portfolio
2024-12-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-024-00696-4 |
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| author | John Karlsson Valik Christian G. Giske Badrul Hasan Mónica Gozalo-Margüello Luis Martínez-Martínez Manica Mueller Premru Žiga Martinčič Bojana Beović Sofia Maraki Maria Zacharioudaki Diamantis Kofteridis Kate McCarthy David Paterson Marina de Cueto Isabel Morales Leonard Leibovici Tanya Babich Fredrik Granath Jesús Rodríguez-Baño Antonio Oliver Dafna Yahav Pontus Nauclér |
| author_facet | John Karlsson Valik Christian G. Giske Badrul Hasan Mónica Gozalo-Margüello Luis Martínez-Martínez Manica Mueller Premru Žiga Martinčič Bojana Beović Sofia Maraki Maria Zacharioudaki Diamantis Kofteridis Kate McCarthy David Paterson Marina de Cueto Isabel Morales Leonard Leibovici Tanya Babich Fredrik Granath Jesús Rodríguez-Baño Antonio Oliver Dafna Yahav Pontus Nauclér |
| author_sort | John Karlsson Valik |
| collection | DOAJ |
| description | Abstract Background Pseudomonas aeruginosa (PA) bloodstream infection (BSI) is a common healthcare-associated complication linked to antimicrobial resistance and high mortality. Ongoing clinical trials are exploring novel anti-virulence agents, yet studies on how bacterial virulence affects PA infection outcomes is conflicting and data from real-world clinical populations is limited. Methods We studied a multicentre cohort of 773 adult patients with PA BSI consecutively collected during 7-years from sites in Europe and Australia. Comprehensive clinical data and whole-genome sequencing of all bacterial strains were obtained. Results Based on the virulence genotype, we identify several virulence clusters, each showing varying proportions of multidrug-resistant phenotypes. Genes tied to biofilm synthesis and epidemic clones ST175 and ST235 are associated with mortality, while the type III secretion system is associated with septic shock. Adding genomic biomarkers to machine learning models based on clinical data indicates improved prediction of severe outcomes in PA BSI patients. Conclusions These findings suggest that virulence markers provide prognostic information with potential applications in guiding adjuvant sepsis treatments. |
| format | Article |
| id | doaj-art-60f9a45c77c340d79f1ba94f12d0e8c5 |
| institution | OA Journals |
| issn | 2730-664X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj-art-60f9a45c77c340d79f1ba94f12d0e8c52025-08-20T01:56:42ZengNature PortfolioCommunications Medicine2730-664X2024-12-014111410.1038/s43856-024-00696-4Genomic virulence markers are associated with severe outcomes in patients with Pseudomonas aeruginosa bloodstream infectionJohn Karlsson Valik0Christian G. Giske1Badrul Hasan2Mónica Gozalo-Margüello3Luis Martínez-Martínez4Manica Mueller Premru5Žiga Martinčič6Bojana Beović7Sofia Maraki8Maria Zacharioudaki9Diamantis Kofteridis10Kate McCarthy11David Paterson12Marina de Cueto13Isabel Morales14Leonard Leibovici15Tanya Babich16Fredrik Granath17Jesús Rodríguez-Baño18Antonio Oliver19Dafna Yahav20Pontus Nauclér21Department of Medicine, Solna, Division of Infectious Diseases, Karolinska InstitutetDepartment of Laboratory Medicine, Karolinska InstitutetDepartment of Laboratory Medicine, Karolinska InstitutetService of Microbiology. Hospital Universitario Marqués de Valdecilla. Instituto de Investigación Marqués de Valdecilla (IDIVAL)Unit of Microbiology, University Hospital Reina SofíaFaculty of Medicine, University of LjubljanaDepartment of Infectious Diseases, University Medical Centre LjubljanaFaculty of Medicine, University of LjubljanaDepartment of Internal Medicine, University Hospital of HeraklionDepartment of Internal Medicine, University Hospital of HeraklionDepartment of Internal Medicine, University Hospital of HeraklionPathology Queensland, Royal Brisbane and Woman’s HospitalUniversity of Queensland Centre for Clinical ResearchUnidad Clínica de Enfermedades Infecciosas y Microbiología, Instituto de Biomedicina de Sevilla (IBiS)/CSIC, Hospital Universitario Virgen Macarena / Departamentos de Medicina y Microbiología, Universidad de SevillaServicio de Urgencias, Hospital Universitario Virgen MacarenaResearch Authority, Rabin Medical Center, Beilinson hospitalResearch Authority, Rabin Medical Center, Beilinson hospitalDepartment of Medicine, Solna, Division of Clinical Epidemiology, Karolinska InstitutetUnidad Clínica de Enfermedades Infecciosas y Microbiología, Instituto de Biomedicina de Sevilla (IBiS)/CSIC, Hospital Universitario Virgen Macarena / Departamentos de Medicina y Microbiología, Universidad de SevillaServicio de Microbiología, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria Illes Balears (IdISBa), CIBERINFECInfectious Diseases Unit, Sheba Medical CenterDepartment of Medicine, Solna, Division of Infectious Diseases, Karolinska InstitutetAbstract Background Pseudomonas aeruginosa (PA) bloodstream infection (BSI) is a common healthcare-associated complication linked to antimicrobial resistance and high mortality. Ongoing clinical trials are exploring novel anti-virulence agents, yet studies on how bacterial virulence affects PA infection outcomes is conflicting and data from real-world clinical populations is limited. Methods We studied a multicentre cohort of 773 adult patients with PA BSI consecutively collected during 7-years from sites in Europe and Australia. Comprehensive clinical data and whole-genome sequencing of all bacterial strains were obtained. Results Based on the virulence genotype, we identify several virulence clusters, each showing varying proportions of multidrug-resistant phenotypes. Genes tied to biofilm synthesis and epidemic clones ST175 and ST235 are associated with mortality, while the type III secretion system is associated with septic shock. Adding genomic biomarkers to machine learning models based on clinical data indicates improved prediction of severe outcomes in PA BSI patients. Conclusions These findings suggest that virulence markers provide prognostic information with potential applications in guiding adjuvant sepsis treatments.https://doi.org/10.1038/s43856-024-00696-4 |
| spellingShingle | John Karlsson Valik Christian G. Giske Badrul Hasan Mónica Gozalo-Margüello Luis Martínez-Martínez Manica Mueller Premru Žiga Martinčič Bojana Beović Sofia Maraki Maria Zacharioudaki Diamantis Kofteridis Kate McCarthy David Paterson Marina de Cueto Isabel Morales Leonard Leibovici Tanya Babich Fredrik Granath Jesús Rodríguez-Baño Antonio Oliver Dafna Yahav Pontus Nauclér Genomic virulence markers are associated with severe outcomes in patients with Pseudomonas aeruginosa bloodstream infection Communications Medicine |
| title | Genomic virulence markers are associated with severe outcomes in patients with Pseudomonas aeruginosa bloodstream infection |
| title_full | Genomic virulence markers are associated with severe outcomes in patients with Pseudomonas aeruginosa bloodstream infection |
| title_fullStr | Genomic virulence markers are associated with severe outcomes in patients with Pseudomonas aeruginosa bloodstream infection |
| title_full_unstemmed | Genomic virulence markers are associated with severe outcomes in patients with Pseudomonas aeruginosa bloodstream infection |
| title_short | Genomic virulence markers are associated with severe outcomes in patients with Pseudomonas aeruginosa bloodstream infection |
| title_sort | genomic virulence markers are associated with severe outcomes in patients with pseudomonas aeruginosa bloodstream infection |
| url | https://doi.org/10.1038/s43856-024-00696-4 |
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