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Monoclonal antibodies against lipopolysaccharide protect against Pseudomonas aeruginosa challenge in mice
Pseudomonas aeruginosa is a common cause of hospital-acquired infections, including central line-associated bloodstream infections and ventilator-associated pneumonia. Unfortunately, effective control of these infections can be difficult, in part due to the prevalence of multi-drug resistant strains...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326049/ https://www.ncbi.nlm.nih.gov/pubmed/37424774 http://dx.doi.org/10.3389/fcimb.2023.1191806 |
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author | Kang, Jason Mateu-Borrás, Margalida Monroe, Hunter L. Sen-Kilic, Emel Miller, Sarah Jo Dublin, Spencer R. Huckaby, Annalisa B. Yang, Evita Pyles, Gage M. Nunley, Mason A. Chapman, Josh A. Amin, Md Shahrier Damron, F. Heath Barbier, Mariette |
author_facet | Kang, Jason Mateu-Borrás, Margalida Monroe, Hunter L. Sen-Kilic, Emel Miller, Sarah Jo Dublin, Spencer R. Huckaby, Annalisa B. Yang, Evita Pyles, Gage M. Nunley, Mason A. Chapman, Josh A. Amin, Md Shahrier Damron, F. Heath Barbier, Mariette |
author_sort | Kang, Jason |
collection | PubMed |
description | Pseudomonas aeruginosa is a common cause of hospital-acquired infections, including central line-associated bloodstream infections and ventilator-associated pneumonia. Unfortunately, effective control of these infections can be difficult, in part due to the prevalence of multi-drug resistant strains of P. aeruginosa. There remains a need for novel therapeutic interventions against P. aeruginosa, and the use of monoclonal antibodies (mAb) is a promising alternative strategy to current standard of care treatments such as antibiotics. To develop mAbs against P. aeruginosa, we utilized ammonium metavanadate, which induces cell envelope stress responses and upregulates polysaccharide expression. Mice were immunized with P. aeruginosa grown with ammonium metavanadate and we developed two IgG2b mAbs, WVDC-0357 and WVDC-0496, directed against the O-antigen lipopolysaccharide of P. aeruginosa. Functional assays revealed that WVDC-0357 and WVDC-0496 directly reduced the viability of P. aeruginosa and mediated bacterial agglutination. In a lethal sepsis model of infection, prophylactic treatment of mice with WVDC-0357 and WVDC-0496 at doses as low as 15 mg/kg conferred 100% survival against challenge. In both sepsis and acute pneumonia models of infection, treatment with WVDC-0357 and WVDC-0496 significantly reduced bacterial burden and inflammatory cytokine production post-challenge. Furthermore, histopathological examination of the lungs revealed that WVDC-0357 and WVDC-0496 reduced inflammatory cell infiltration. Overall, our results indicate that mAbs directed against lipopolysaccharide are a promising therapy for the treatment and prevention of P. aeruginosa infections. |
format | Online Article Text |
id | pubmed-10326049 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103260492023-07-08 Monoclonal antibodies against lipopolysaccharide protect against Pseudomonas aeruginosa challenge in mice Kang, Jason Mateu-Borrás, Margalida Monroe, Hunter L. Sen-Kilic, Emel Miller, Sarah Jo Dublin, Spencer R. Huckaby, Annalisa B. Yang, Evita Pyles, Gage M. Nunley, Mason A. Chapman, Josh A. Amin, Md Shahrier Damron, F. Heath Barbier, Mariette Front Cell Infect Microbiol Cellular and Infection Microbiology Pseudomonas aeruginosa is a common cause of hospital-acquired infections, including central line-associated bloodstream infections and ventilator-associated pneumonia. Unfortunately, effective control of these infections can be difficult, in part due to the prevalence of multi-drug resistant strains of P. aeruginosa. There remains a need for novel therapeutic interventions against P. aeruginosa, and the use of monoclonal antibodies (mAb) is a promising alternative strategy to current standard of care treatments such as antibiotics. To develop mAbs against P. aeruginosa, we utilized ammonium metavanadate, which induces cell envelope stress responses and upregulates polysaccharide expression. Mice were immunized with P. aeruginosa grown with ammonium metavanadate and we developed two IgG2b mAbs, WVDC-0357 and WVDC-0496, directed against the O-antigen lipopolysaccharide of P. aeruginosa. Functional assays revealed that WVDC-0357 and WVDC-0496 directly reduced the viability of P. aeruginosa and mediated bacterial agglutination. In a lethal sepsis model of infection, prophylactic treatment of mice with WVDC-0357 and WVDC-0496 at doses as low as 15 mg/kg conferred 100% survival against challenge. In both sepsis and acute pneumonia models of infection, treatment with WVDC-0357 and WVDC-0496 significantly reduced bacterial burden and inflammatory cytokine production post-challenge. Furthermore, histopathological examination of the lungs revealed that WVDC-0357 and WVDC-0496 reduced inflammatory cell infiltration. Overall, our results indicate that mAbs directed against lipopolysaccharide are a promising therapy for the treatment and prevention of P. aeruginosa infections. Frontiers Media S.A. 2023-06-22 /pmc/articles/PMC10326049/ /pubmed/37424774 http://dx.doi.org/10.3389/fcimb.2023.1191806 Text en Copyright © 2023 Kang, Mateu-Borrás, Monroe, Sen-Kilic, Miller, Dublin, Huckaby, Yang, Pyles, Nunley, Chapman, Amin, Damron and Barbier https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cellular and Infection Microbiology Kang, Jason Mateu-Borrás, Margalida Monroe, Hunter L. Sen-Kilic, Emel Miller, Sarah Jo Dublin, Spencer R. Huckaby, Annalisa B. Yang, Evita Pyles, Gage M. Nunley, Mason A. Chapman, Josh A. Amin, Md Shahrier Damron, F. Heath Barbier, Mariette Monoclonal antibodies against lipopolysaccharide protect against Pseudomonas aeruginosa challenge in mice |
title | Monoclonal antibodies against lipopolysaccharide protect against Pseudomonas aeruginosa challenge in mice |
title_full | Monoclonal antibodies against lipopolysaccharide protect against Pseudomonas aeruginosa challenge in mice |
title_fullStr | Monoclonal antibodies against lipopolysaccharide protect against Pseudomonas aeruginosa challenge in mice |
title_full_unstemmed | Monoclonal antibodies against lipopolysaccharide protect against Pseudomonas aeruginosa challenge in mice |
title_short | Monoclonal antibodies against lipopolysaccharide protect against Pseudomonas aeruginosa challenge in mice |
title_sort | monoclonal antibodies against lipopolysaccharide protect against pseudomonas aeruginosa challenge in mice |
topic | Cellular and Infection Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326049/ https://www.ncbi.nlm.nih.gov/pubmed/37424774 http://dx.doi.org/10.3389/fcimb.2023.1191806 |
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