Potentials of organic tellurium-containing compound AS101 to overcome carbapenemase-producing Escherichia coli

Tsung-Ying Yang; Wei-Chun Hung; Tsung-Han Tsai; Po-Liang Lu; Sheng-Fan Wang; Liang-Chun Wang; Yu-Tzu Lin; Sung-Pin Tseng

doi:10.1016/j.jmii.2023.07.002

Potentials of organic tellurium-containing compound AS101 to overcome carbapenemase-producing Escherichia coli

J Microbiol Immunol Infect. 2023 Oct;56(5):1016-1025. doi: 10.1016/j.jmii.2023.07.002. Epub 2023 Jul 16.

Authors

Tsung-Ying Yang¹, Wei-Chun Hung², Tsung-Han Tsai³, Po-Liang Lu⁴, Sheng-Fan Wang³, Liang-Chun Wang⁵, Yu-Tzu Lin⁶, Sung-Pin Tseng⁷

Affiliations

¹ Department of Medical Laboratory Science, I-Shou University, Kaohsiung, Taiwan; Research Organization for Nano and Life Innovation, Future Innovation Institute, Waseda University, Japan; Research Institute for Science and Engineering, Waseda University, Japan; School of Education, Waseda University, Japan.
² Department of Microbiology and Immunology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
³ Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁴ Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
⁵ Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan.
⁶ Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan. Electronic address: yutzulin@mail.cmu.edu.tw.
⁷ Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan; Graduate Institute of Animal Vaccine Technology, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, Taiwan; Center for Tropical Medicine and Infectious Disease Research, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: tsengsp@kmu.edu.tw.

PMID: 37516546
DOI: 10.1016/j.jmii.2023.07.002

Abstract

Background: The issue of carbapenem-resistant Escherichia coli was aggravated yearly. The previous studies reported the varied but critical epidemiology of carbapenem-resistant E. coli among which the carbapenemase-producing strains were regarded as one of the most notorious issues. AS101, an organic tellurium-containing compound undergoing clinical trials, was revealed with antibacterial activities. However, little is known about the antibacterial effect of AS101 against carbapenemase-producing E. coli (CPEC).

Materials and methods: The minimum inhibitory concentration (MIC) of AS101 against the 15 isolates was examined using a broth microdilution method. The scanning electron microscopy, pharmaceutical manipulations, reactive oxygen species level, and DNA fragmentation assay were carried out to investigate the antibacterial mechanism. The sepsis mouse model was employed to assess the in vivo treatment effect.

Results: The bla_NDM (33.3%) was revealed as the dominant carbapenemase gene among the 15 CPEC isolates, followed by the bla_KPC gene (26.7%). The MICs of AS101 against the 15 isolates ranged from 0.5 to 32 μg/ml, and 99.9% of bacterial eradication was observed at 8 h, 4 h, and 2 h for 1×, 2×, and 4 × MIC, respectively. The mechanistic investigations suggest that AS101 would enter the bacterial cell, and induce ROS generation, leading to DNA fragmentation. The in vivo study exhibited that AS101 possessed a steady treatment effect in a sepsis mouse model, with an up to 83.3% of survival rate.

Conclusion: The in vitro activities, mechanisms, and in vivo study of AS101 against CPEC were unveiled. Our finding provided further evidence for the antibiotic development of AS101.

Keywords: AS101; Carbapenem resistance; Escherichia coli; Mouse sepsis model.