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Broad-spectrum suppression of bacterial pneumonia by aminoglycoside-propagated Acinetobacter baumannii

Antimicrobial resistance is increasing in pathogenic bacteria. Yet, the effect of antibiotic exposure on resistant bacteria has been underexplored and may affect pathogenesis. Here we describe the discovery that propagation of the human pathogen Acinetobacter baumannii in an aminoglycoside antibioti...

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Autores principales: Hood-Pishchany, M. Indriati, Pham, Ly, Wijers, Christiaan D., Burns, William J., Boyd, Kelli L., Palmer, Lauren D., Skaar, Eric P., Noto, Michael J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094866/
https://www.ncbi.nlm.nih.gov/pubmed/32168364
http://dx.doi.org/10.1371/journal.ppat.1008374
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author Hood-Pishchany, M. Indriati
Pham, Ly
Wijers, Christiaan D.
Burns, William J.
Boyd, Kelli L.
Palmer, Lauren D.
Skaar, Eric P.
Noto, Michael J.
author_facet Hood-Pishchany, M. Indriati
Pham, Ly
Wijers, Christiaan D.
Burns, William J.
Boyd, Kelli L.
Palmer, Lauren D.
Skaar, Eric P.
Noto, Michael J.
author_sort Hood-Pishchany, M. Indriati
collection PubMed
description Antimicrobial resistance is increasing in pathogenic bacteria. Yet, the effect of antibiotic exposure on resistant bacteria has been underexplored and may affect pathogenesis. Here we describe the discovery that propagation of the human pathogen Acinetobacter baumannii in an aminoglycoside antibiotic results in alterations to the bacterium that interact with lung innate immunity resulting in enhanced bacterial clearance. Co-inoculation of mice with A. baumannii grown in the presence and absence of the aminoglycoside, kanamycin, induces enhanced clearance of a non-kanamycin-propagated strain. This finding can be replicated when kanamycin-propagated A. baumannii is killed prior to co-inoculation of mice, indicating the enhanced bacterial clearance results from interactions with innate host defenses in the lung. Infection with kanamycin-propagated A. baumannii alters the kinetics of phagocyte recruitment to the lung and reduces pro- and anti-inflammatory cytokine and chemokine production in the lung and blood. This culminates in reduced histopathologic evidence of lung injury during infection despite enhanced bacterial clearance. Further, the antibacterial response induced by killed aminoglycoside-propagated A. baumannii enhances the clearance of multiple clinically relevant Gram-negative pathogens from the lungs of infected mice. Together, these findings exemplify cooperation between antibiotics and the host immune system that affords protection against multiple antibiotic-resistant bacterial pathogens. Further, these findings highlight the potential for the development of a broad-spectrum therapeutic that exploits a similar mechanism to that described here and acts as an innate immunity modulator.
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spelling pubmed-70948662020-04-03 Broad-spectrum suppression of bacterial pneumonia by aminoglycoside-propagated Acinetobacter baumannii Hood-Pishchany, M. Indriati Pham, Ly Wijers, Christiaan D. Burns, William J. Boyd, Kelli L. Palmer, Lauren D. Skaar, Eric P. Noto, Michael J. PLoS Pathog Research Article Antimicrobial resistance is increasing in pathogenic bacteria. Yet, the effect of antibiotic exposure on resistant bacteria has been underexplored and may affect pathogenesis. Here we describe the discovery that propagation of the human pathogen Acinetobacter baumannii in an aminoglycoside antibiotic results in alterations to the bacterium that interact with lung innate immunity resulting in enhanced bacterial clearance. Co-inoculation of mice with A. baumannii grown in the presence and absence of the aminoglycoside, kanamycin, induces enhanced clearance of a non-kanamycin-propagated strain. This finding can be replicated when kanamycin-propagated A. baumannii is killed prior to co-inoculation of mice, indicating the enhanced bacterial clearance results from interactions with innate host defenses in the lung. Infection with kanamycin-propagated A. baumannii alters the kinetics of phagocyte recruitment to the lung and reduces pro- and anti-inflammatory cytokine and chemokine production in the lung and blood. This culminates in reduced histopathologic evidence of lung injury during infection despite enhanced bacterial clearance. Further, the antibacterial response induced by killed aminoglycoside-propagated A. baumannii enhances the clearance of multiple clinically relevant Gram-negative pathogens from the lungs of infected mice. Together, these findings exemplify cooperation between antibiotics and the host immune system that affords protection against multiple antibiotic-resistant bacterial pathogens. Further, these findings highlight the potential for the development of a broad-spectrum therapeutic that exploits a similar mechanism to that described here and acts as an innate immunity modulator. Public Library of Science 2020-03-13 /pmc/articles/PMC7094866/ /pubmed/32168364 http://dx.doi.org/10.1371/journal.ppat.1008374 Text en © 2020 Hood-Pishchany et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hood-Pishchany, M. Indriati
Pham, Ly
Wijers, Christiaan D.
Burns, William J.
Boyd, Kelli L.
Palmer, Lauren D.
Skaar, Eric P.
Noto, Michael J.
Broad-spectrum suppression of bacterial pneumonia by aminoglycoside-propagated Acinetobacter baumannii
title Broad-spectrum suppression of bacterial pneumonia by aminoglycoside-propagated Acinetobacter baumannii
title_full Broad-spectrum suppression of bacterial pneumonia by aminoglycoside-propagated Acinetobacter baumannii
title_fullStr Broad-spectrum suppression of bacterial pneumonia by aminoglycoside-propagated Acinetobacter baumannii
title_full_unstemmed Broad-spectrum suppression of bacterial pneumonia by aminoglycoside-propagated Acinetobacter baumannii
title_short Broad-spectrum suppression of bacterial pneumonia by aminoglycoside-propagated Acinetobacter baumannii
title_sort broad-spectrum suppression of bacterial pneumonia by aminoglycoside-propagated acinetobacter baumannii
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094866/
https://www.ncbi.nlm.nih.gov/pubmed/32168364
http://dx.doi.org/10.1371/journal.ppat.1008374
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