Evidence map›Paper›PMID 39052750›Full record

ArticleThe Journal of infectious diseases2024

In Vivo Evolution of a Klebsiella pneumoniae Capsule Defect With wcaJ Mutation Promotes Complement-Mediated Opsonophagocytosis During Recurrent Infection.

William Bain, Brian Ahn, Hernán F Peñaloza, Christi L McElheny, Nathanial Tolman, Rick van der Geest, Shekina Gonzalez-Ferrer, Nathalie Chen, Xiaojing An, Ria Hosuru and 19 more

Abstract read
In one paragraph

Article in The Journal of infectious diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed.

  1. Article
  2. Article
  3. Differential virulence potential of different clades of multidrug-resistantmedRxiv : the preprint server for health sciences · 2026
    Article
  4. Connections betweenInfection and immunity · 2026
    Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. mBio · 2025
    Article
  12. Review
  13. Prevalence and features of hypervirulentInfection and immunity · 2025
    Review
  14. Virulence · 2024
    Review
  15. Co-occurrence of ST412mSystems · 2024
    Article
  16. Editorial: Immune response to gram-negative bacteria in the lungs.Frontiers in cellular and infection microbiology · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors.

William BainDivision of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh.ORCID 0000-0001-8506-0552
Brian AhnDivision of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus School of Medicine, Denver.
Hernán F PeñalozaDivision of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh.
Christi L McElhenyDivision of Infectious Diseases, Department of Medicine.
Nathanial TolmanDivision of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh.
Rick van der GeestDivision of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh.
Shekina Gonzalez-FerrerDivision of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh.
Nathalie ChenDivision of Infectious Diseases, Department of Medicine.
Xiaojing AnDivision of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh.
Ria HosuruDivision of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh.
Mohammadreza TabaryDivision of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh.
Erin PapkeDivision of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh.
Naina KohliDivision of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh.
Nauman FarooqDepartment of Critical Care Medicine.
William BachmanDivision of Infectious Diseases, Department of Medicine.
Tolani F OlonisakinDivision of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh.
Zeyu XiongDivision of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh.
Marissa P GriffithDivision of Infectious Diseases, Department of Medicine.
Mara SullivanCenter for Biologic Imaging, Department of Cell Biology.
Jonathan FranksCenter for Biologic Imaging, Department of Cell Biology.
Mustapha M MustaphaDivision of Infectious Diseases, Department of Medicine.
Alina IovlevaDivision of Infectious Diseases, Department of Medicine.
Tomeka SuberDivision of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh.
Robert Q ShanksDepartment of Ophthalmology, University of Pittsburgh, Pennsylvania.ORCID 0000-0002-7699-5396
Viviana P FerreiraDepartment of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Ohio.ORCID 0000-0001-8923-5671
Donna B StolzCenter for Biologic Imaging, Department of Cell Biology.ORCID 0000-0002-1833-7010
Daria Van TyneDivision of Infectious Diseases, Department of Medicine.ORCID 0000-0001-7284-0103
Yohei DoiDivision of Infectious Diseases, Department of Medicine.ORCID 0000-0002-9620-2525
Janet S LeeDivision of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh.ORCID 0000-0002-6812-6043

Funding

Regulation of Cardiolin Byosynthesis in Epithelial InjuryP01HL114453 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MALLAMPALLI, RAMA K · 2014 to 2023
$21.3M
Mechanisms of host protection against pathogen-secreted proteases in acute lung injuryR01HL136143 · NHLBI · WASHINGTON UNIVERSITY · PI LEE, JANET SOJUNG · 2017 to 2024
$4.4M
The role of ACOD1 in immunomodulation in intrapulmonary Klebsiella pneumoniae infectionR01HL142084 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHEN, KONG · 2018 to 2021
$2.4M
Pittsburgh Innovation in Collaborative Training of Residents AllianceR38HL150207 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Charles S Dela Cruz, Corrine R Kliment · 2020 to 2026
$2.1M
Spatiotemporal control of early matricellular events in the injured lungR01HL177904 · NHLBI · WASHINGTON UNIVERSITY · PI Jaehyung Cho, Janet Sojung Lee · 2025 to 2026
$1.5M
Patient-Oriented Research in Acute Lung Injury and Host Defense in the ICUK24HL143285 · NHLBI · WASHINGTON UNIVERSITY · PI LEE, JANET SOJUNG · 2019 to 2023
$579k
Platelet factors attenuate alveolar injury during severe pneumoniaIK2BX004886 · VA · VETERANS HEALTH ADMINISTRATION · PI BAIN, WILLIAM G · 2020 to 2024
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BLRD VA IK2 BX004886NHLBI NIH HHS K24 HL143285NHLBI NIH HHS P01 HL114453NHLBI NIH HHS R01 HL136143NHLBI NIH HHS R01 HL142084NHLBI NIH HHS R01 HL177904NHLBI NIH HHS R38 HL150207NIH HHSVA
6 · The paper itself

Abstract

backgroundKlebsiella pneumoniae carbapenemase-producing K pneumoniae (KPC-Kp) bloodstream infections are associated with high mortality. We studied clinical bloodstream KPC-Kp isolates to investigate mechanisms of resistance to complement, a key host defense against bloodstream infection.

methodsWe tested growth of KPC-Kp isolates in human serum. In serial isolates from a single patient, we performed whole genome sequencing and tested for complement resistance and binding by mixing study, direct enzyme-linked immunosorbent assay, flow cytometry, and electron microscopy. We utilized an isogenic deletion mutant in phagocytosis assays and an acute lung infection model.

resultsWe found serum resistance in 16 of 59 (27%) KPC-Kp clinical bloodstream isolates. In 5 genetically related bloodstream isolates from a single patient, we noted a loss-of-function mutation in the capsule biosynthesis gene, wcaJ. Disruption of wcaJ was associated with decreased polysaccharide capsule, resistance to complement-mediated killing, and surprisingly, increased binding of complement proteins. Furthermore, an isogenic wcaJ deletion mutant exhibited increased opsonophagocytosis in vitro and impaired in vivo control in the lung after airspace macrophage depletion in mice.

conclusionsLoss of function in wcaJ led to increased complement resistance, complement binding, and opsonophagocytosis, which may promote KPC-Kp persistence by enabling coexistence of increased bloodstream fitness and reduced tissue virulence.

Indexed as

Bacterial CapsulesComplement System ProteinsKlebsiella InfectionsKlebsiella pneumoniaePhagocytosisAnimalsBacteremiaBacterial ProteinsFemaleHumansMiceMutationReinfectionWhole Genome SequencingBacterial ProteinsComplement System ProteinscapsulecarbapenemasecomplementKlebsiella pneumoniaewcaJ

Identifiers

PMID39052750
PMCPMC11272070

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.