image: This image shows E. coli bacteria infecting a mouse bladder. We found that urinary tract infections caused by this E. coli strain can provoke a protective immune response that prevents recurrent infections, whereas another E. coli strain could hide from the immune system and cause recurrent infections. view more
Credit: Valerie P. O'Brien and Washington University Center for Cellular Imaging
Genetically diverse bacterial strains that cause urinary tract infections differ in their ability to trigger protective immune responses in mice, potentially explaining why these infections frequently recur in many patients, according to a study published December 13 in the open-access journal PLOS Pathogens by Thomas Hannan and Scott Hultgren of Washington University School of Medicine, and colleagues. As noted by the authors, the study suggests that the development of a broad-spectrum vaccine should take into account the genetically diverse pathogens that women encounter in the community.
Many patients suffer from highly recurrent urinary tract infections caused by Escherichia coli, which are genetically diverse bacteria. Recurrent episodes are often caused by the same E. coli strain that caused the first infection, suggesting that some patients may not develop a protective immune response. A better understanding of host-pathogen interactions is urgently needed for effective drug and vaccine development in the era of increasing antibiotic resistance. To address this gap in knowledge, Hannan and Hultgren used a mouse model to compare the effects of two E. coli strains that cause urinary tract infections.
They found that one strain, UTI89, could infect the bladder indefinitely, whereas strain CFT073 was always cleared within eight weeks. After mice had a CFT073 infection and antibiotic treatment, they were protected from a CFT073 challenge infection, but were susceptible to a UTI89 challenge infection. By contrast, mice with a UTI89 infection and antibiotics were susceptible to recurrent urinary tract infections when challenged with either strain. Depleting T cells, immune cells important for developing protection against infection, prevented mice from clearing their CFT073 infections and made them susceptible to recurrent CFT073 urinary tract infections. The findings show that infection with one E. coli strain could trigger a protective immune response, while another strain sidestepped this response. According to the authors, the results shed new light on immune responses to urinary tract infections and may be important for drug and vaccine development.
The authors conclude, "This study shows that some bacteria hide from the immune system to cause urinary tract infections again and again."
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Research Article
Funding: This work was supported by the National Institutes of Health and Office of Research on Women's Health Specialized Center of Research (P50 DK64540 and R01 DK51406 to SJH; U01 AI95542 to SJH), URL: https://orwh.od.nih.gov; the National Institutes of Health Mucosal Immunology Studies Team consortium (U01 AI095776 Young Investigator Award and Mentored Clinical Scientist Research Career Development Award K08 AI083746 to TJH), URL: https://www.mucosal.org/; and the National Science Foundation (Graduate Research Fellowship #DGE -114395 to VPO), URL: https://www.nsfgrfp.org/. As well, scanning electron microscopy sample preparation was conducted at the Washington University Research Center for Auditory and Vestibular Studies, which is supported by the National Institutes of Health NIDCD Grant P30DC04665; and sample preparation and imaging was conducted at the Washington University Center for Cellular Imaging (WUCCI), which is supported by the Washington University School of Medicine, The Children's Discovery Institute of Washington University and St. Louis Children's Hospital (CDI-CORE-2015-505) and the Foundation for Barnes-Jewish Hospital (3770). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Citation: O'Brien VP, Dorsey DA, Hannan TJ, Hultgren SJ (2018) Host restriction of Escherichia coli recurrent urinary tract infection occurs in a bacterial strain-specific manner. PLoS Pathog 14(12): e1007457. https://doi.org/10.1371/journal.ppat.1007457
Author Affiliations:
Department of Molecular Microbiology and Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, Missouri, United States of America
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America
In your coverage please use this URL to provide access to the freely available paper: http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007457
Journal
PLoS Pathogens