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Peptide Developed to Combat Tuberculosis

Peptide Developed to Combat TuberculosisThere has emerged a Peptide developed to combat Tuberculosis and it is showing interest around the world. Iztli 1, a peptide developed at the Cellular Physiology Institute (IFC) and already patented in Mexico, could become an antibiotic to combat tuberculosis.


It was called Iztli in honor of Tezcatlipoca, a god who carried an obsidian knife, which was the sacred dagger Iztli or Tecpatl, used by the Aztecs in human sacrifices.

The Iztli peptide (IP-1), designed by Gabriel del Río and collaborators, is a molecular missile that (already tested in mice) reduces lung damage caused by tuberculosis and helps the body kill the bacterium Mycobacterium tuberculosis (MTB) .

Peptide Developed to Combat Tuberculosis – What it Means

Ending MTB is a challenge for medicine because the bacterium has evolved to avoid the defense mechanisms of macrophages (a type of immune system cell responsible for protecting the body from harmful bacteria) and has also become resistant to antibiotics in common use.

Iztli or IP-1 is made up of two amino acid sequences. One, created from brewer’s yeast, recognizes the target cells: in this case the Saccharomyces cerevisiae pheromone . The other complements the first to generate a sequence with antimicrobial activity.

It was tested in brewer’s yeast cells because, like human cells, they are eukaryotes and share similar genes with us.

Can TB be Completely Cured?

Del Río discovered that the combination of his two attributes: being a hunter and a murderer at the same time, gives the Iztli 1 peptide other emergent properties. In mammalian cells and microscopic fungi such as yeast, it activates autophagy, a natural process to deal with MTB infection.

Autophagy eliminates damaged parts of the cell and the bacteria that invade its interior. Thus, the Iztli 1 peptide, by activating it, facilitates the natural response of macrophages to MTB infection. At the same time, the peptide is capable of directly killing MTB bacteria, so that even bacteria resistant to antibiotics or to the body’s natural response may be sensitive to this double activity of the peptide.

How long is TB recovery?

As a final result, the MTB dies and the immune system repairs the damage caused by this bacteria.

That IP-1 kills MTB from within the cell while also helping to get rid of the bacteria, leads Del Río and his group to postulate that it could cure not only tuberculosis, but also other antibiotic-resistant infectious diseases. .

Currently, antibiotics that attack microbes or activate the immune system are used in the treatment of infections, but neither is designed for both targets. The Iztli 1 peptide is the first in that class of molecules.

A preclinical study, carried out by Del Río and his group in a mouse model that replicates tuberculosis, showed that Iztli does have this therapeutic activity.

What are the 3 stages of tuberculosis?

When administering IP-1 in rodents, it was observed that it reduces the damage caused by MTB: the bacteria is found in less quantity in the lungs and there are more protective cytokines (proteins of the immune system that act as regulators of the body’s immune response). .

The next phase will be to test the Iztli 1 peptide in humans to check its efficacy against antibiotic-resistant tuberculosis. With this purpose, the collaboration of the health sector is expected to initiate clinical trials.

Meanwhile, Del Río and his group are developing computational tools to design more selective peptides, with emerging properties, that can be applied, at an experimental level, in the treatment of various microbial infections and in conditions associated with aging, such as cancer.

The expectation is that IP-1 (or other molecules capable of inducing autophagy in humans) could also eliminate cell components that accumulate damage during aging, thus reducing the possibility of cancer.

How long can a TB patient live?

3.6 years is the average life expectancy of TB sufferers however some cases can see a longer life.

 The Iztli 1 peptide created at UNAM has its antecedents in the hunter-killer peptides created in the United States for cancer treatment.

Del Río participated in this project, which was carried out at the Buck Institute for Research on Aging (the first institute for aging and associated diseases, created in the United States) between 1999 and 2004.

The hunter-killers are the fusion of two peptides. Hunter , which selectively recognizes a tissue, is coupled with killer , which is a selective antibacterial cationic peptide (SCAP).

The killer , says Del Río, kills the cell by damaging the activity of the mitochondria, which is for the cell like the Federal Electricity Commission for Mexico: generator of energy.

In humans, antibacterial peptides (amino acid sequences) function as a protective barrier against infection. “They are our bullets.”

Most are cationic: they have a positive charge, so they prefer to bind to the membrane of bacteria or mitochondria, which is electro-negative.

Is there a vaccine for tuberculosis?

Iztli 1 peptide one is a smaller molecule compared to hunter-killer peptides . That it be a shorter version, emphasizes Del Río, favors its activity and makes its production more economical.

In the multifunctional Iztli peptides project, in addition to postgraduate students with theses under the direction of Del Río, seven groups from UNAM, the Autonomous University of the State of Mexico (UAEM), the National Institute of Medical Sciences and Nutrition Salvador Zubirán (INCMNSZ) and the Mexican Social Security Institute (IMSS).

Measurement of the three-dimensional structure of the Iztli peptide, by crystallography and X-rays: Alfredo Torres (IFC).

Measurement of the secondary structure of peptides with circular dichroism: Georgina Garza (Faculty of Medicine, UNAM).

Determination of non-covalent contacts of peptide amino acid residues by nuclear magnetic resonance: Carlos Amero (UAEM).

Measurement of isolated mitochondria as in whole cells: Antonio Peña and Salvador Uribe (IFC).

Experimental design of genetics and confocal microscopy to validate the activities of Iztli peptides: Roberto Coria (IFC).

Evaluation of autophagy activity: Susana Castro (Institute of Biotechnology, UNAM).

Evaluation of antituberculosis activity in mice: Rogelio Hernández Pando (INCMNSZ) and Bruno Rivas (IMSS).