Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Treatment With a Neutrophil Elastase Inhibitor and Ofloxacin Reduces P. Aeruginosa Burden in a Mouse Model of Chronic Suppurative Otitis Media Publisher Pubmed



Khomtchouk KM1 ; Joseph LI1 ; Khomtchouk BB2 ; Kouhi A3 ; Massa S1 ; Xia A1 ; Koliesnik I4 ; Pletzer D5 ; Bollyky PL4 ; Santa Maria PL1
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Otolaryngology, Head and Neck Surgery, Stanford University, Stanford, CA, United States
  2. 2. Department of Medicine, Section of Computational Biomedicine and Biomedical Data Science, University of Chicago, Chicago, IL, United States
  3. 3. Department of Otolaryngology, Head and Neck Surgery, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Medicine, Infectious Diseases, Stanford University, Stanford, CA, United States
  5. 5. Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand

Source: npj Biofilms and Microbiomes Published:2021


Abstract

Chronic suppurative otitis media (CSOM) is a widespread, debilitating problem with poorly understood immunology. Here, we assess the host response to middle ear infection over the course of a month post-infection in a mouse model of CSOM and in human subjects with the disease. Using multiparameter flow cytometry and a binomial generalized linear machine learning model, we identified Ly6G, a surface marker of mature neutrophils, as the most informative factor of host response driving disease in the CSOM mouse model. Consistent with this, neutrophils were the most abundant cell type in infected mice and Ly6G expression tracked with the course of infection. Moreover, neutrophil-specific immunomodulatory treatment using the neutrophil elastase inhibitor GW 311616A significantly reduces bacterial burden relative to ofloxacin-only treated animals in this model. The levels of dsDNA in middle ear effusion samples are elevated in both humans and mice with CSOM and decreased during treatment, suggesting that dsDNA may serve as a molecular biomarker of treatment response. Together these data strongly implicate neutrophils in the ineffective immune response to P. aeruginosa infection in CSOM and suggest that immunomodulatory strategies may benefit drug-tolerant infections for chronic biofilm-mediated disease. © 2021, The Author(s).
Related Docs
1. A Novel Mouse Model of Chronic Suppurative Otitis Media and Its Use in Preclinical Antibiotic Evaluation, Science Advances (2020)
2. Cinnamomum: The New Therapeutic Agents for Inhibition of Bacterial and Fungal Biofilm-Associated Infection, Frontiers in Cellular and Infection Microbiology (2022)
3. The Biofilm-Associated Bacterial Infections Unrelated to Indwelling Devices, IUBMB Life (2020)
4. Minimally Invasive Trans-Tympanic Eustachian Tube Occlusion Animal Model, International Journal of Pediatric Otorhinolaryngology (2022)
5. Advanced Strategies for Combating Bacterial Biofilms, Journal of Cellular Physiology (2019)
Experts (# of related papers)
Ali Kouhi (2)