Dietary restriction of iron availability attenuates UPEC pathogenesis in a mouse model of urinary tract infection

Author:

Bauckman Kyle A.1,Matsuda Rina1,Higgins Cassandra B.2,DeBosch Brian J.2,Wang Caihong13,Mysorekar Indira U.143

Affiliation:

1. Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri

2. Department of Pediatrics, Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri

3. Centre for Reproductive Health Sciences, Washington University School of Medicine, St. Louis, Missouri

4. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri

Abstract

Iron is a critical nutrient required by hosts and pathogens. Uropathogenic Escherichia coli (UPEC), the principal causative agent of urinary tract infections (UTIs), chelate iron for their survival and persistence. Here, we demonstrate that dietary modulation of iron availability limits UPEC burden in a mouse model of UTI. Mice on a low-iron diet exhibit reduced systemic and bladder mucosal iron availability and harbor significantly lower bacterial burden, concomitant with dampened inflammation. Hepcidin is a master regulator of iron that controls iron-dependent UPEC intracellular growth. Hepcidin-deficient mice ( Hamp1−/−) exhibit accumulation of iron deposits, persistent bacterial burden in the bladder, and a heightened inflammatory response to UTI. However, a low-iron dietary regimen reversed the iron overload and increased bacterial burden phenotypes in Hamp1−/− mice. Thus modulation of iron levels via diet can reduce UPEC infection and persistence, which may have significant implications for clinical management of UTI.

Funder

NIH

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publisher

American Physiological Society

Subject

Physiology

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