In Vivo Bioluminescence Imaging for Targeting Acute Hypoxic/Ischemic Small Intestine with Engineered Salmonella typhimurium

Chung-Man Moon; Jin Hai Zheng; Jung-Joon Min; Yong Yeon Jeong; Suk-Hee Heo; Sang-Soo Shin

doi:10.1016/j.omtm.2020.06.021

In Vivo Bioluminescence Imaging for Targeting Acute Hypoxic/Ischemic Small Intestine with Engineered Salmonella typhimurium

Mol Ther Methods Clin Dev. 2020 Jun 25:18:484-492. doi: 10.1016/j.omtm.2020.06.021. eCollection 2020 Sep 11.

Authors

Chung-Man Moon^{1

2}, Jin Hai Zheng^{3

4}, Jung-Joon Min⁵, Yong Yeon Jeong⁶, Suk-Hee Heo⁶, Sang-Soo Shin⁷

Affiliations

¹ Quantitative Medical Imaging Section, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.
² Research Institute of Medical Sciences, Chonnam National University, Gwangju, Republic of Korea.
³ College of Biology, Hunan University, Changsha, Hunan, China.
⁴ Laboratory of In Vivo Molecular Imaging, Institute for Molecular Imaging and Theranostics, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
⁵ Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Republic of Korea.
⁶ Department of Radiology, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
⁷ Department of Radiology, Chonnam National University Medical School and Chonnam National University Hospital, Gwangju, Republic of Korea.

Abstract

This study aimed at investigating the feasibility of bioluminescence imaging (BLI) with engineered Salmonella typhimurium (ΔppGpp S. typhimurium) for visualizing acute hypoxic/ischemic bowels. At the start of 12- or 24-h reperfusion, ΔppGpp S. typhimurium was injected into the lateral tail veins of rats in which three segments of the small intestine were respectively subjected to 2, 3, and 4 h of ischemia. BLI and magnetic resonance imaging were performed at each reperfusion time point. Bioluminescence was exclusively detected in the hypoxic/ischemic segment of the intestine, showing the ability of ΔppGpp S. typhimurium to specifically target and proliferate in a hypoxic/ischemic area. Serial monitoring of these rat models revealed a progressive increase in bacterial bioluminescence in the ischemic intestines in conjunction with viable bacterial counts. The viable bacterial counts were positively correlated with lactate dehydrogenase levels after 24 h of reperfusion following 3 or 4 h of ischemia as well as interleukin-6 levels after 24 h of reperfusion following 4 h of ischemia. Our findings demonstrated that BLI was able to detect the acute hypoxic/ischemic bowel via monitoring of the distribution, internalization, and activity of administered ΔppGpp S. typhimurium. These findings may be useful for the early diagnosis of ischemic bowel disease.

Keywords: Salmonella typhimurium; acute mesenteric ischemia; bioluminescence imaging.