P1-76 The Lack of Toll-like Receptor 11 Expression in Mice Does Not Allow for Colonization by Shiga Toxin-producing Escherichia coli

Monday, July 10, 2017
Exhibit Hall (Tampa Convention Center)
Lisa Harrison , CFSAN , Laurel , MD
Prabha Kc , CFSAN , Laurel , MD
Monika Proszkowiec-Weglarz , CFSAN , Laurel , MD
Uma Babu , CFSAN , Laurel , MD
Andrew Do , CFSAN , Laurel , MD
Mohammad Alam , U.S. Food and Drug Administration, CFSAN , Laurel , MD
Kristina Williams , CFSAN , Laurel , MD
Kannan Balan , U.S. Food and Drug Administration, CFSAN , Laurel , MD
Introduction:  Shiga toxin-producing Escherichia coli (STEC) continue to be an important public health problem in the United States as they have serious foodborne disease outcomes, including acute renal failure and death. Currently, characterization of STEC is performed using molecular methods and in vitro models due to the lack of suitable animal models.

Purpose:  STEC do not cause disease in wild-type (WT) mice, possibly due to several differences between mouse and human intestines. One such difference is the presence of the innate immune receptor Toll-like receptor 11 (TLR11) in mice. In order to determine whether TLR11 prevents STEC colonization and infection in mice, we used TLR11-knockout (KO) mice in STEC challenges.

Methods:  WT or TLR11-KO mice were orally gavaged with 109 CFU STEC (Ampicillin-resistant O26:H11 strain EC1649) and observed for signs of disease and bacterial shedding. Eight to ten days postchallenge, small intestines, large intestines, ceca, kidneys, spleens, and livers were harvested, homogenized, and plated on ampicillin plates for colony counts.

Results: Both TLR11-KO mice and WT mice showed no signs of distress or disease postchallenge. However, WT mice continued to shed STEC longer than TLR11-KO mice. Organs of TLR11-KO mice contained no detectable STEC, while a few WT mice had low levels of STEC in their large intestines and ceca.

Significance:  FDA’s food safety mission requires research tools to characterize microbial contaminants in our food supply in order to distinguish between pathogenic and nonpathogenic bacteria. The identification of an animal model for STEC is critical for characterization of disease outcome, elucidating infectious dose of different STEC serotypes, confirming molecular and in vitro methods, and for traceback analyses. This investigation demonstrated that TLR11-KO mice are not a suitable animal model for STEC. It is useful to present negative outcomes so that animal challenges are not unnecessarily repeated.