Team:UPF Barcelona/Description

Team:UPF Barcelona - 2021.igem.org

Project

Description and overview

ARIA team in fighting a highly complex and multifactorial problem with an innovative point of view.

Problem: the silent pandemic of the 21st century

Antibiotic treatment is one of the main approaches of modern medicine used to treat infectious diseases. Its discovery implied a turning point in the history of medicine, and therefore in pharmacology development. After years of misuse of this incredible finding in several spheres as the clinic and food industry, negative selective pressure and the power of evolution have led to a massive landscape of antibiotic resistance genes [1]. Combinations of those genes supply bacteria with the tools to overcome drugs’ pharmacokinetics, which can be achieved via multiple mechanisms such as efflux pump, limitation of the drugs’ uptake, modification of its target structure, or simply by its inactivation [2].

The image shows different mechanisms that can undergo antibiotic resistance. On the bottom left an efflux pump is ejecting the drug out from the cell. On the top left, the drug’s target has been modified blocking the interaction between both. On the bottom right, an alternative enzyme is inactivating the drug. On the top right, an acquired structure is preventing the drug from entering the cell.

Figure 1: Different mechanisms of antibiotic resistance: efflux pump (1), modification of drug’s target (2), limitation of drug’s uptake (3), and drug inactivation (4).

Antibiotic resistance (AR) does occur naturally, but there are few factors that have accelerated the process:

A symbolic diagram represents how the world will end up collapsing due to the crisis caused by antibiotic resistance. The factors contributing to this issue are the following:

Misuse and overuse of antimicrobials in humans, animals and plants.
Inadequate access to clean water, sanitation and hygiene.
Poor infection and disease prevention.
Inequality in vaccine, antimicrobials and diagnostics distribution.
Weak food safety and waste management systems.

Figure 2: Factors accelerating AR. Data provided by No Time to Wait: Securing the future from drug-resistant infections [4].

A recent report (2019) from the Interagency Coordination Group (IACG) [3] on Antimicrobial Resistance showed the following statistics predicting AR impact:

Drug-resistant diseases already cause 700 000 deaths every year. Nowadays, 230 000 of them are from untreatable tuberculosis. That number could increase to 10 million per year by 2050.
The economic damage could be comparable to the 2008 global financial crisis.
In low-income countries, investments are urgently needed to address this issue.

The diagram represents in a schematic way how antibiotic resistance will impact different aspects of our society. Various facts and data are given:

Drug-resistant diseases already cause 700 000 deaths every year. Nowadays, 230 000 of them are from untreatable tuberculosis. That number could increase to 10 million per year by 2050.
The economic damage could be comparable to the 2008 global financial crisis.
In low-income countries, investments are urgently needed to address this issue.

Figure 3: The Antibiotic Resistance impact. Data provided by No Time to Wait: Securing the future from drug-resistant infections [4].

If investments and action are further delayed, the world will have to cope with the disastrous impact of uncontrolled antimicrobial resistance.

— Interagency Coordination Group on Antimicrobial Resistance, 2019

Solution: Antibiotic Resistance Inference Array (ARIA)

To prevent this silent pandemic from collapsing our world in the near future, all of our efforts must be directed towards fighting antimicrobial resistance.

This is where ARIA plays an important role, proposing a key strategy for tackling this multidimensional problem.

We have developed both biotechnological and computational tools that will work synergically in order to offer an integrated solution. Our main aim is to characterize antibiotic resistant strains through three coupled systems: Alpha, Alexandria and Omega. Our proposal starts by seeking personalized bacterial gene configurations to study, then detecting the presence of specific resistances in a biological sample, and ending up with a list of suggested treatments for clinicians. More details about it are available in the project design page.

In the image, the three main systems of ARIA are represented with a graphic symbol. Two arrows represent the complementarity between those.

Figure 4: Complementation between ARIA’s computational and biotechnological systems.

References

[1] Wright G. The antibiotic resistome: the nexus of chemical and genetic diversity. Nat Rev Microbiol. 2007;5:175–186.https://doi.org/10.1038/nrmicro1614

[2] Reygaert WC. An overview of the antimicrobial resistance mechanisms of bacteria. AIMS Microbiol. 2018;4(3):482-501. http://www.aimspress.com/article/10.3934/microbiol.2018.3.482

[3] World Health Organization (WHO). Antibiotic resistance fact sheet. Updated July 5, 2020. https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance

[4] Interagency Coordination Group on Antimicrobial Resistance. No Time to Wait: Securing the future from drug-resistant infections. Report to the Secretary-General of the United Nations. April 2019.