Klebsiella pneumoniae induces host metabolic stress that promotes tolerance to pulmonary infection

Lung, Tania Wong Fok; Charytonowicz, Daniel; Beaumont, Kristin G.; Shah, Shivang S.; Sridhar, Shwetha Hara; Gorrie, Claire L.; Mu, Andre; Hofstaedter, Casey E.; Varisco, David J.; McConville, Thomas H.; Drikic, Marija; Fowler, Brandon; Urso, Andreacarola; We, Shi; Fucich, Dario; Annavajhala, Medini K.; Khan, Ibrahim N.; Oussenko, Irina; Francoeur, Nancy; Smith, Melissa; Stockwell, Brent R.; Lewis, Ian A.; Hachani, Abderrahman; Baskota, Swikrity Upadhyay; Uhlemann, Anne‐Catrin; Ahn, Danielle; Ernst, Robert K.; Howden, Benjamin P; Sebra, Robert; Prince, Alice

doi:10.1016/j.cmet.2022.03.009

Cited by 49 publications

(67 citation statements)

References 86 publications

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“…In the context of infection, itaconate reduces the TLR-triggered secretion of inflammatory cytokines ( Li et al., 2013 ). Specifically, in mouse models of pneumonia, itaconate was identified as a common molecule in the airway metabolome contributing to bacterial pathogenesis ( Riquelme et al., 2020 ; Tomlinson et al., 2021 ; Wong Fok Lung et al., 2022 ).…”

Section: Itaconate Participates In Anti-inflammatory Cascadesmentioning

confidence: 99%

“…Even organisms that do not metabolize itaconate can benefit from its presence by altering their own metabolic activity to thwart immune clearance. The expression of Irg1 by myeloid cells is also a major component of the anti-inflammatory milieu leading to infection tolerance ( Wong Fok Lung et al., 2022 ). Metabolically active K. pneumoniae ST258 strains induce ROS-generating pathways, myeloid-derived suppressor cell (MDSCs) recruitment, and abundant itaconate release in the airway ( Ahn et al., 2016 ; Wong Fok Lung et al., 2022 ).…”

Section: Itaconate Participates In Anti-inflammatory Cascadesmentioning

confidence: 99%

“…The expression of Irg1 by myeloid cells is also a major component of the anti-inflammatory milieu leading to infection tolerance ( Wong Fok Lung et al., 2022 ). Metabolically active K. pneumoniae ST258 strains induce ROS-generating pathways, myeloid-derived suppressor cell (MDSCs) recruitment, and abundant itaconate release in the airway ( Ahn et al., 2016 ; Wong Fok Lung et al., 2022 ). Itaconate helps to control K. pneumoniae infection, as there is a significantly increased bacterial burden in Irg1 -/– mice ( Wong Fok Lung et al., 2022 ).…”

Section: Itaconate Participates In Anti-inflammatory Cascadesmentioning

confidence: 99%

“…Metabolically active K. pneumoniae ST258 strains induce ROS-generating pathways, myeloid-derived suppressor cell (MDSCs) recruitment, and abundant itaconate release in the airway ( Ahn et al., 2016 ; Wong Fok Lung et al., 2022 ). Itaconate helps to control K. pneumoniae infection, as there is a significantly increased bacterial burden in Irg1 -/– mice ( Wong Fok Lung et al., 2022 ). However, the presence of itaconate enables the infected mice to tolerate remarkably high levels of infection ( Wong Fok Lung et al., 2022 ).…”

Section: Itaconate Participates In Anti-inflammatory Cascadesmentioning

confidence: 99%

“…The release of anti-inflammatory metabolites at the site of infection can affect pathogenesis in two major ways: It can alter the function of host immune cells and it can drive changes in bacterial metabolic activity, selecting for the variants that are optimally fit to persist. This creates a setting of tissue tolerance, in which the host-adapted pathogen and the locally immunosuppressed host generate a state of persistent infection ( Schneider and Ayres, 2008 ; Wong Fok Lung et al., 2022 ), as found in TB, COPD, cystic fibrosis and other common infections.…”

Section: Introductionmentioning

confidence: 99%

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Anti-Inflammatory Metabolites in the Pathogenesis of Bacterial Infection

Urso

Prince

2022

Front. Cell. Infect. Microbiol.

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Host and pathogen metabolism have a major impact on the outcome of infection. The microenvironment consisting of immune and stromal cells drives bacterial proliferation and adaptation, while also shaping the activity of the immune system. The abundant metabolites itaconate and adenosine are classified as anti-inflammatory, as they help to contain the local damage associated with inflammation, oxidants and proteases. A growing literature details the many roles of these immunometabolites in the pathogenesis of infection and their diverse functions in specific tissues. Some bacteria, notably P. aeruginosa, actively metabolize these compounds, others, such as S. aureus respond by altering their own metabolic programs selecting for optimal fitness. For most of the model systems studied to date, these immunometabolites promote a milieu of tolerance, limiting local immune clearance mechanisms, along with promoting bacterial adaptation. The generation of metabolites such as adenosine and itaconate can be host protective. In the setting of acute inflammation, these compounds also represent potential therapeutic targets to prevent infection.

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Section: Itaconate Participates In Anti-inflammatory Cascadesmentioning

confidence: 99%

Section: Itaconate Participates In Anti-inflammatory Cascadesmentioning

confidence: 99%

Section: Itaconate Participates In Anti-inflammatory Cascadesmentioning

confidence: 99%

Section: Itaconate Participates In Anti-inflammatory Cascadesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Anti-Inflammatory Metabolites in the Pathogenesis of Bacterial Infection

Urso

Prince

2022

Front. Cell. Infect. Microbiol.

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Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2021–2022

Harvey

2024

Mass Spectrometry Reviews

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The use of matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry for the analysis of carbohydrates and glycoconjugates is a well‐established technique and this review is the 12th update of the original article published in 1999 and brings coverage of the literature to the end of 2022. As with previous review, this review also includes a few papers that describe methods appropriate to analysis by MALDI, such as sample preparation, even though the ionization method is not MALDI. The review follows the same format as previous reviews. It is divided into three sections: (1) general aspects such as theory of the MALDI process, matrices, derivatization, MALDI imaging, fragmentation, quantification and the use of computer software for structural identification. (2) Applications to various structural types such as oligo‐ and polysaccharides, glycoproteins, glycolipids, glycosides and biopharmaceuticals, and (3) other general areas such as medicine, industrial processes, natural products and glycan synthesis where MALDI is extensively used. Much of the material relating to applications is presented in tabular form. MALDI is still an ideal technique for carbohydrate analysis, particularly in its ability to produce single ions from each analyte and advancements in the technique and range of applications show little sign of diminishing.

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Synergistic Effects of Baicalin and Levofloxacin Against Hypervirulent Klebsiella pneumoniae Biofilm In Vitro

Han

Luo

et al. 2023

Curr Microbiol

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Klebsiella pneumoniae induces host metabolic stress that promotes tolerance to pulmonary infection

Cited by 49 publications

References 86 publications

Anti-Inflammatory Metabolites in the Pathogenesis of Bacterial Infection

Anti-Inflammatory Metabolites in the Pathogenesis of Bacterial Infection

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2021–2022

Synergistic Effects of Baicalin and Levofloxacin Against Hypervirulent Klebsiella pneumoniae Biofilm In Vitro

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