Tissue compartmentalization enables <i>Salmonella</i> persistence during chemotherapy
Jiagui Li, Beatrice Claudi, Joseph Fanous, Natalia Chicherova, Francesca Romana Cianfanelli, Robert A. A. Campbell, Dirk Bumann
Abstract
Significance Some infections are exceedingly difficult to cure, even with adequate antimicrobial chemotherapy. How pathogens can survive exposure to antimicrobials in tissues remains poorly understood. Using three-dimensional whole-organ tomography, we show that Salmonella colonization of the mouse spleen is uneven. Low Salmonella density in the white pulp triggers only limited local infiltration by inflammatory cells that are crucial for supporting antimicrobial Salmonella clearance. Inflammatory cell density declines further during treatment in response to receding Salmonella loads, resulting in insufficient support for clearance and eradication failure. However, sustaining inflammation during antimicrobial chemotherapy enables effective clearance. Our findings identify heterogeneous host–pathogen interactions in compartmentalized tissues as a main mechanism underlying the antibiotic persistence of Salmonella .