Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Disruption of staphylococcal aggregation protects against lethal lung injury
Jaime L. Hook, … , Sunita Bhattacharya, Jahar Bhattacharya
Jaime L. Hook, … , Sunita Bhattacharya, Jahar Bhattacharya
Published February 12, 2018
Citation Information: J Clin Invest. 2018;128(3):1074-1086. https://doi.org/10.1172/JCI95823.
View: Text | PDF
Research Article Cell biology Pulmonology Article has an altmetric score of 4

Disruption of staphylococcal aggregation protects against lethal lung injury

  • Text
  • PDF
Abstract

Infection by Staphylococcus aureus strain USA300 causes tissue injury, multiorgan failure, and high mortality. However, the mechanisms by which the bacteria adhere to, then stabilize on, mucosal surfaces before causing injury remain unclear. We addressed these issues through the first real-time determinations of USA300-alveolar interactions in live lungs. We found that within minutes, inhaled USA300 established stable, self-associated microaggregates in niches at curved, but not at flat, regions of the alveolar wall. The microaggregates released α-hemolysin toxin, causing localized alveolar injury, as indicated by epithelial dye loss, mitochondrial depolarization, and cytosolic Ca2+ increase. Spread of cytosolic Ca2+ through intercellular gap junctions to adjoining, uninfected alveoli caused pulmonary edema. Systemic pretreatment with vancomycin, a USA300-cidal antibiotic, failed to protect mice infected with inhaled WT USA300. However, vancomycin pretreatment markedly abrogated mortality in mice infected with mutant USA300 that lacked the aggregation-promoting factor PhnD. We interpret USA300-induced mortality as having resulted from rapid bacterial aggregation in alveolar niches. These findings indicate, for the first time to our knowledge, that alveolar microanatomy is critical in promoting the aggregation and, hence, in causing USA300-induced alveolar injury. We propose that in addition to antibiotics, strategies for bacterial disaggregation may constitute novel therapy against USA300-induced lung injury.

Authors

Jaime L. Hook, Mohammad N. Islam, Dane Parker, Alice S. Prince, Sunita Bhattacharya, Jahar Bhattacharya

×

Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 Total
Citations: 2 4 4 6 4 4 8 32
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2021 (4)

Title and authors Publication Year
Actin fence therapy with exogenous V12Rac1 protects against Acute Lung Injury
Galina A Gusarova, Shonit Das, Mohammad Naimul Islam, Kristin Westphalen, Guangchun Jin, Igor O Shmarakov, Li Li, Sunita Bhattacharya, Jahar Bhattacharya
JCI Insight 2021
Acute respiratory distress syndrome
NJ Meyer, L Gattinoni, CS Calfee
Lancet 2021
IL-33–mediated Eosinophilia Protects against Acute Lung Injury
PA Krishack, MK Hollinger, TG Kuzel, TS Decker, TJ Louviere, CL Hrusch, AI Sperling, PA Verhoef
American journal of respiratory cell and molecular biology 2021
Staphylococcus aureus Arsenal To Conquer the Lower Respiratory Tract
M Pivard, K Moreau, F Vandenesch, PD Fey
mSphere 2021

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Posted by 5 X users
On 4 Facebook pages
46 readers on Mendeley
See more details