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A dual-therapy approach for the treatment of biofilm-mediated Salmonella gallbladder carriage

Asymptomatic carriage of Salmonella Typhi continues to facilitate the transmission of typhoid fever, resulting in 14 million new infections and 136,000 fatalities each year. Asymptomatic chronic carriage of S. Typhi is facilitated by the formation of biofilms on gallstones that protect the bacteria...

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Autores principales: Sandala, Jenna L., Eichar, Bradley W., Kuo, Laura G., Hahn, Mark M., Basak, Akash K., Huggins, William M., Woolard, Katherine, Melander, Christian, Gunn, John S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793255/
https://www.ncbi.nlm.nih.gov/pubmed/33370414
http://dx.doi.org/10.1371/journal.ppat.1009192
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author Sandala, Jenna L.
Eichar, Bradley W.
Kuo, Laura G.
Hahn, Mark M.
Basak, Akash K.
Huggins, William M.
Woolard, Katherine
Melander, Christian
Gunn, John S.
author_facet Sandala, Jenna L.
Eichar, Bradley W.
Kuo, Laura G.
Hahn, Mark M.
Basak, Akash K.
Huggins, William M.
Woolard, Katherine
Melander, Christian
Gunn, John S.
author_sort Sandala, Jenna L.
collection PubMed
description Asymptomatic carriage of Salmonella Typhi continues to facilitate the transmission of typhoid fever, resulting in 14 million new infections and 136,000 fatalities each year. Asymptomatic chronic carriage of S. Typhi is facilitated by the formation of biofilms on gallstones that protect the bacteria from environmental insults and immune system clearance. Here, we identified two unique small molecules capable of both inhibiting Salmonella biofilm growth and disrupting pre-formed biofilm structures without affecting bacterial viability. In a mouse model of chronic gallbladder Salmonella carriage, treatment with either compound reduced bacterial burden in the gallbladder by 1–2 logs resulting in bacterial dissemination to peripheral organs that was associated with increased mortality. Co-administration of either compound with ciprofloxacin not only enhanced compound efficacy in the gallbladder by a further 1–1.5 logs for a total of 3–4.5 log reduction, but also prevented bacterial dissemination to peripheral organs. These data suggest a dual-therapy approach targeting both biofilm and planktonic populations can be further developed as a safe and efficient treatment of biofilm-mediated chronic S. Typhi infections.
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spelling pubmed-77932552021-01-27 A dual-therapy approach for the treatment of biofilm-mediated Salmonella gallbladder carriage Sandala, Jenna L. Eichar, Bradley W. Kuo, Laura G. Hahn, Mark M. Basak, Akash K. Huggins, William M. Woolard, Katherine Melander, Christian Gunn, John S. PLoS Pathog Research Article Asymptomatic carriage of Salmonella Typhi continues to facilitate the transmission of typhoid fever, resulting in 14 million new infections and 136,000 fatalities each year. Asymptomatic chronic carriage of S. Typhi is facilitated by the formation of biofilms on gallstones that protect the bacteria from environmental insults and immune system clearance. Here, we identified two unique small molecules capable of both inhibiting Salmonella biofilm growth and disrupting pre-formed biofilm structures without affecting bacterial viability. In a mouse model of chronic gallbladder Salmonella carriage, treatment with either compound reduced bacterial burden in the gallbladder by 1–2 logs resulting in bacterial dissemination to peripheral organs that was associated with increased mortality. Co-administration of either compound with ciprofloxacin not only enhanced compound efficacy in the gallbladder by a further 1–1.5 logs for a total of 3–4.5 log reduction, but also prevented bacterial dissemination to peripheral organs. These data suggest a dual-therapy approach targeting both biofilm and planktonic populations can be further developed as a safe and efficient treatment of biofilm-mediated chronic S. Typhi infections. Public Library of Science 2020-12-28 /pmc/articles/PMC7793255/ /pubmed/33370414 http://dx.doi.org/10.1371/journal.ppat.1009192 Text en © 2020 Sandala 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
Sandala, Jenna L.
Eichar, Bradley W.
Kuo, Laura G.
Hahn, Mark M.
Basak, Akash K.
Huggins, William M.
Woolard, Katherine
Melander, Christian
Gunn, John S.
A dual-therapy approach for the treatment of biofilm-mediated Salmonella gallbladder carriage
title A dual-therapy approach for the treatment of biofilm-mediated Salmonella gallbladder carriage
title_full A dual-therapy approach for the treatment of biofilm-mediated Salmonella gallbladder carriage
title_fullStr A dual-therapy approach for the treatment of biofilm-mediated Salmonella gallbladder carriage
title_full_unstemmed A dual-therapy approach for the treatment of biofilm-mediated Salmonella gallbladder carriage
title_short A dual-therapy approach for the treatment of biofilm-mediated Salmonella gallbladder carriage
title_sort dual-therapy approach for the treatment of biofilm-mediated salmonella gallbladder carriage
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793255/
https://www.ncbi.nlm.nih.gov/pubmed/33370414
http://dx.doi.org/10.1371/journal.ppat.1009192
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