Demonstrate

Appropriate attribution is half of success.

Proof Of Concept
Background
Abstract
Reference

Proof Of Concept
Background
Abstract
Reference

Background

Bacteria are the main pathogen of human communicable disease during the past years. In 14 century, The Black Death plague caused by Yersinia pestis led over 75 million people death in the world, and Cholera caused by Vibrio cholera became global pandemic for eight times. In 1907, Typhoid bacillus was found the the arch-criminal of Typhoid Mary event. However, the table was turned by the discovery of penicillin in 1928. And new category of antibiotics had been discovered rapidly during the following years. Antibiotic therapy has saved countless lives.

But for the abuse of antibiotics, in 21th century, a spreading of drug resistance appears. When the antibiotics kill pathogenic bacteria, some of them mutating and developing the "drug-resistance". Drug resistant bacteria flourish in the absence of diminished competition, and the resistance can be transferred among the bacteria, which made their infections considerable mortality and morbidity [1]. Furthermore, the prevalence of the infections is still increasing by abused antibiotics and resistance spreading. It is predicted that 10 million people would be killed for the drug-resistant pathogen infections each year by 2050 [2]. Multidrug-resistant (MDR) pathogens has been identified as one of the top three threats to human health by the World Health Organization (WHO) [3].

Bacteria develop clinically significant resistance in a period of just months to years. The new antimicrobials or modifications of current arsenal may not address the trends in resistance effectively [3]. Combination therapies for the treatment are needed urgently [1].

Abstract

Our team supposed to construct programmable bacteria for combating specific pathogens. Following the theory of “input to render-loop to output”, we designed two models. Model 1 can be divided into four parts: sensor, killer, toggle switch and lysis. We performed it by constructing a gene circuit which can detect the gram-negative bacteria and release toxins to kill the target bacteria. Model 2 was composed of three parts: sensor, killer and self-destruction switch. We built one circuit for the model examination, by which the engineered bacterium can lyse synchronously and release M13 phages. Multiple functional components of each model lead varies functions of the whole circuit when the three parts assembled.

Reference

[1] Brooks, B. D., & Brooks, A. E. (2014). Therapeutic strategies to combat antibiotic resistance. Advanced Drug Delivery Reviews, 78(C), 14–27.
[2] McCullough, A. R., Parekh, S., Rathbone, J., Del Mar, C. B., & Hoffmann, T. C. (2016). A systematic review of the public's knowledge and beliefs about antibiotic resistance. Journal o Antimicrobial Chemotherapy, 71(1), 27–33.
[3] Worthington, R. J., & Melander, C. (2013). Combination approaches to combat multidrug-resistant bacteria. Trends in Biotechnology, 31(3), 179–186.