Team:Tec-Monterrey/Description

DESCRIPTION

Problematic

Many people think that we are at the beginning of the post-antibiotic era due to antimicrobial resistance, which has become a serious problem all around the world in the last decades. This resistance reduces the effectiveness of medications and bacterial infections become more frequent, long-lasting and harder to attack. Bacterial resistance has reached such an uncontrolled level that now bacteria like Acinetobacter and Pseudomonas have become super-resistant [5]. This means that they are almost immune to all antibiotics used to fight them and are especially dangerous in hospitals and health care centers.

Project focus

To raise awareness about the great impact that antibiotic resistance has on the life quality of people, we decided to focus our project on a disease in which super-bacteria have severe repercussions. This disease is Cystic Fibrosis (CF) and about 80% of deaths are caused by these microorganisms [3]. CF is the most common hereditary disease affecting white people of northern European ancestry, having 1 in 2000–3000 births [3].

Diagnosed patients experience an accumulation of viscous mucus within their lungs, pancreas and digestive tract, giving place to an approximate life expectancy of 37.5 years (18, in Mexico). [1] CF patients are especially susceptible to bacterial infections, mainly those caused by Pseudomonas aeruginosa, because the mucus provides the perfect environment for their proliferation and prevents them from being easily expelled.

What is Cystic Fibrosis?

Cystic Fibrosis is a disease caused by a mutation in the CFTR gene, which encodes the information for the synthesis of an ion channel, which keeps the osmotic balance between chloride ions, influencing the movement of water between tissues. The most common mutation is a deletion of a phenylalanine, impairing the function of the channel, producing an unusable protein that lacks the ability to efficiently transport chloride ions, and giving place to a deficiency of water in the mucus [2].

The viscous mucus that is produced by CF patients is considerably different from the one of healthy individuals, due to one of the main components in mucus: mucines. These molecules are glycoproteins that give mucus its viscosity. In addition, patients have shown to possess abnormal glycosylations in their mucins, primarily of sialic acid and fucose. The large concentration of sialic acid has shown to be related to the increment in viscosity [6] and to the increase on the incidence of infections [4].

As a consequence, this produces continuous coughing, masculine infertility, nutritional problems, recurring infections and an overall decrement in life quality, giving place to an approximate life expectancy of 37.5 years (18, in Mexico) [1].

Working plan

Having these concerns in mind, iGEM team Tec-Monterrey 2019 came up with a working plan which consists in the development of a platform that allows us to find new antibiotics for the treatment against Pseudomonas aeruginosa. However, in order for the antibiotic to work properly, it is necessary to contribute to its diffusion through the mucus. Thus, to achieve this objective we propose 5 different whole-cell biosensors that may facilitate the discovery of new antibiotics followed up by a mucolytic that reduces the viscosity of CF patients' mucus.

Main objectives:

Therefore we established two main objectives:

• To produce 5 whole cell biosensors able to detect the mechanism of action of unknown compounds with possible antibiotic properties.
• To produce a recombinant protein able to reduce mucus viscosity in CF patients using a novel method that facilitates the recovery process.

HARDWARE

See the design of our device!!

DESIGN

See the details of our working plan!!

MODEL

Check out our mathematical model!!

References:

1. Davies, J. C., Alton, E. W., & Bush, A. (2007). Cystic fibrosis. BMJ (Clinical research ed.), 335(7632), 1255–1259. doi:10.1136/bmj.39391.713229.AD
2. National Guideline Alliance (UK). Cystic Fibrosis: Diagnosis and management. London: National Institute for Health and Care Excellence (UK); 2017 Oct 25. (NICE Guideline, No. 78.) Available from: https://www.ncbi.nlm.nih.gov/books/NBK464183/
3. Rafeeq, M. M., & Murad, H. A. S. (2017). Cystic fibrosis: current therapeutic targets and future approaches. Journal of translational medicine, 15(1), 84.
4. Venkatakrishnan, V., Thaysen-Andersen, M., Chen, S. C., Nevalainen, H., & Packer, N. H. (2014). Cystic fibrosis and bacterial colonization define the sputum N-glycosylation phenotype. Glycobiology, 25(1), 88-100
5. WHO (2017). Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. World Health Organization. Web site: https://www.who.int/medicines/publications/global-priority-list-antibiotic-resistant-bacteria/en/
6. Zanin, M., Baviskar, P., Webster, R., & Webby, R. (2016). The Interaction between Respiratory Pathogens and Mucus. Cell host & microbe, 19(2), 159–168. doi:10.1016/j.chom.2016.01.001