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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-12-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1009192 |
| _version_ | 1819017200470589440 |
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| author | Jenna L Sandala Bradley W Eichar Laura G Kuo Mark M Hahn Akash K Basak William M Huggins Katherine Woolard Christian Melander John S Gunn |
| author_facet | Jenna L Sandala Bradley W Eichar Laura G Kuo Mark M Hahn Akash K Basak William M Huggins Katherine Woolard Christian Melander John S Gunn |
| author_sort | Jenna L Sandala |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-21T02:59:45Z |
| format | Article |
| id | doaj.art-6987b1dfdd31401380798923c2b8d863 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-21T02:59:45Z |
| publishDate | 2020-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-6987b1dfdd31401380798923c2b8d8632022-12-21T19:18:13ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742020-12-011612e100919210.1371/journal.ppat.1009192A dual-therapy approach for the treatment of biofilm-mediated Salmonella gallbladder carriage.Jenna L SandalaBradley W EicharLaura G KuoMark M HahnAkash K BasakWilliam M HugginsKatherine WoolardChristian MelanderJohn S GunnAsymptomatic 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.https://doi.org/10.1371/journal.ppat.1009192 |
| spellingShingle | Jenna L Sandala Bradley W Eichar Laura G Kuo Mark M Hahn Akash K Basak William M Huggins Katherine Woolard Christian Melander John S Gunn A dual-therapy approach for the treatment of biofilm-mediated Salmonella gallbladder carriage. PLoS Pathogens |
| 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 |
| url | https://doi.org/10.1371/journal.ppat.1009192 |
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