Tissue compartmentalization enables; Salmonella; persistence during chemotherapy

Li, Jiagui and Claudi, Beatrice and Fanous, Joseph and Chicherova, Natalia and Cianfanelli, Francesca Romana and Campbell, Robert A. A. and Bumann, Dirk. (2021) Tissue compartmentalization enables; Salmonella; persistence during chemotherapy. Proceedings of the National Academy of Sciences of the United States of America, 118 (51). e2113951118.

[img] PDF - Published Version
Available under License CC BY-NC-ND (Attribution-NonCommercial-NoDerivatives).


Official URL: https://edoc.unibas.ch/87038/

Downloads: Statistics Overview


Antimicrobial chemotherapy can fail to eradicate the pathogen, even in the absence of antimicrobial resistance. Persisting pathogens can subsequently cause relapsing diseases. In vitro studies suggest various mechanisms of antibiotic persistence, but their in vivo relevance remains unclear because of the difficulty of studying scarce pathogen survivors in complex host tissues. Here, we localized and characterized rare surviving; Salmonella; in mouse spleen using high-resolution whole-organ tomography. Chemotherapy cleared >99.5% of the; Salmonella; but was inefficient against a small; Salmonella; subset in the white pulp. Previous models could not explain these findings: drug exposure was adequate,; Salmonella; continued to replicate, and host stresses induced only limited; Salmonella; drug tolerance. Instead, antimicrobial clearance required support of; Salmonella; -killing neutrophils and monocytes, and the density of such cells was lower in the white pulp than in other spleen compartments containing higher; Salmonella; loads. Neutrophil densities declined further during treatment in response to receding; Salmonella; loads, resulting in insufficient support for; Salmonella; clearance from the white pulp and eradication failure. However, adjunctive therapies sustaining inflammatory support enabled effective clearance. These results identify uneven; Salmonella; tissue colonization and spatiotemporal inflammation dynamics as main causes of; Salmonella; persistence and establish a powerful approach to investigate scarce but impactful pathogen subsets in complex host environments.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Bumann)
UniBasel Contributors:Bumann, Dirk
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
edoc DOI:
Last Modified:07 Mar 2022 09:06
Deposited On:07 Mar 2022 09:06

Repository Staff Only: item control page