TOfrom scorpion venom Diplocentrus melicioriginally from Veracruz, Lourival Possani Postay, a researcher at the Institute of Biotechnology, Morelos campus, UNAM – in collaboration with Rogelio Hernández Pando, from the National Institute of Medical Sciences and Nutrition Salvador Zubirán (INCMNSZ), and Richard Zare, from Stanford University, in California, United States –, managed to develop two new antibiotics that have proven to be quite effective against Mycobacterium tuberculosisbacteria that cause tuberculosis, and Stahaphylococcus aureusa pathogen that can cause everything from skin infections to pneumonia, septicemia, meningitis, endocarditis and osteomyelitis, especially in hospital environments.

“From the venom of the scorpion Diplocentrus melici We managed to isolate two colorless molecules, called benzoquinones, which when in contact with air oxidize and change color: one turns blue and the other red, as well as we managed to determine their structure and synthesize them. The blue acts against Mycobacterium tuberculosis and the red against Stahaphylococcus aureus” indicates Possani Postay.

The part that had to do with Mycobacterium tuberculosis and the disease it causes in humans was addressed by Hernández Pando, who is a recognized pathologist, in his INCMNSZ laboratory.

“As Dr. Hernández Pando has the possibility of inducing tuberculosis in a murine model, he was able to analyze the effect of benzoquinone blue and concluded that it is a very good antibiotic against this disease. Later, at the Institute of Biotechnology, we continued the study and discovered that it can also kill other bacteria such as Acinetobacter baumannii”, adds the university researcher.

And to determine the structure of both molecules and synthesize them, Possani Postay turned to Dr. Zare, a renowned chemist at Stanford University.

“This was because in my laboratory at the Institute of Biotechnology we can only determine the structure of proteins and peptides, not that of benzoquinones, which are heterocyclic compounds that do not contain amino acids,” he explains.

Medical tests and financial support

According to the World Health Organization (WHO), internationally tuberculosis is the leading cause of death from an infectious pathogen, one of the top ten causes of mortality and one of the leading causes of deaths related to antimicrobial resistance.

Although this condition is preventable and curable, it is present in all countries and age groups. It is estimated that in 2024, 10.7 million people worldwide contracted it (5.8 million men, 3.7 million women and 1.2 million children) and that 1.23 million died as a result of it (150 thousand had the human immunodeficiency virus).

Mycobacterium tuberculosis It usually affects the lungs and is transmitted through the air with the coughs, sneezes or spitting of a sick person.

For the WHO, the so-called drug-resistant tuberculosis has unleashed a public health crisis and already represents a threat to health security (what’s more, it classifies M. tuberculosis as a critical priority bacteria).

Regarding conditions caused by Stahaphylococcus aureusare acquired more frequently by people with a compromised or weakened immune system (because this bacteria has also developed resistance to conventional antibiotics, the WHO considers it a high priority).

Now, Hernández Pando is testing different types of nanoparticles to better stabilize and protect the two new antibiotics and, in this way, introduce them into the body. Furthermore, both molecules already have a patent in Mexico and South Africa.

“What follows is to carry out the clinical trials; however, these involve great expense. Hopefully a Mexican pharmaceutical company will help us to carry them out and mass produce the two new antibiotics,” concludes Possani Postay.

Spicy, but… benign

Pseudomonas aeruginosa It is an opportunistic bacteria that causes havoc in patients admitted to hospitals and in people with weakened immune systems, that is, with cystic fibrosis, burns, chronic obstructive pulmonary disease (COPD), cancer, acquired immunodeficiency syndrome (AIDS)…

Infections caused by this bacteria (pneumonia, sepsis, and urinary tract, ear, eye, skin, and wound infections) can be very serious and potentially fatal.

Because Pseudomonas aeruginosa has developed resistance to conventional antibiotics, the World Health Organization considers it a high priority bacteria.

Fortunately, a group of researchers from the Department of Molecular Medicine and Bioprocesses of the Institute of Biotechnology, Morelos campus, UNAM, led by Gerardo Corzo Burguete – in collaboration with Georgina Estrada Tapia, from the Yucatán Scientific Research Center (CICY) – discovered, in the habanero chile (Capsicum chinense Jacq.), a peptide called defensin J1-1, from which he invented a biotechnological process to obtain a new antibiotic, XisHar J1-1, very effective against Pseudomonas aeruginosa (It could also be against fungi).

First, a genetically modified bacteria is obtained that generates defensin J1-1, then this bacteria is grown in submerged fermentation, a technique used in industry to produce compounds in large quantities, and finally defensin J1-1 is extracted and purified.

“In our tests we do not use a strain of Pseudomonas aeruginosa resistant to conventional antibiotics and extracted from patients, but one that is used to characterize antimicrobial peptides… Furthermore, defensin J1-1 and some variants of it, all produced synthetically, already have a Mexican patent,” says Estrada Tapia.

The challenges

The next step is to test the antibiotic XisHar J1-1 now on a strain of Pseudomonas aeruginosa resistant to conventional antibiotics and extracted from patients.

“If we are successful in this, and I believe we will be because both strains, although different, are of the same species, preclinical trials would come in an authorized laboratory; and then, clinical trials with patients,” says Iván Arenas Sosa, a member of Corzo Burguete’s team at the UNAM Institute of Biotechnology.

There are still other challenges for researchers, because defensin J1-1 and its variants may be susceptible to degradation in different organisms.

“That is why it is very important to continue investigating which is the most appropriate form of this molecule to carry out preclinical trials,” says Estrada Tapia.

In Arenas Sosa’s opinion, with this molecule, formulations could also be made to treat some skin wounds infected with Pseudomonas aeruginosa and other bacteria.

“We still have a long way to go. We hope that the technological transfer of defensin J1-1 will be carried out soon,” he adds.

“The problem of antibiotic-resistant bacteria has increased in recent years and will continue to do so in the future. Hence, it is essential to support research projects focused on the discovery of new molecules or the application of new useful treatments to combat antimicrobial resistance,” he concludes.