Antibiotic resistance: a global threat that still has a solution

Tec de Monterrey student proposes in a scientific study a strategy to reduce the phenomenon of antimicrobial resistance, a serious public health problem worldwide.

By Michael Ramírez 
 

In the year 2055, a dystopian future, Fernanda is in labor, but the situation is complicated and doctors must perform a cesarean section. This surgery, which decades ago was a routine intervention and even a low risk, is now a death sentence, since the usual antibiotics that were previously used to reduce the risk of infections in wounds, today have ceased to have an effect on the human being.

The anecdote is evidently fictitious, but the phenomenon is real: it is called antimicrobial resistance (AMR), and occurs when microorganisms, such as bacteria, are no longer affected by an antibiotic and acquire the ability to resist its effects.

World Health Organization notes in an official bulletin, “Since antibiotics began to be used, scientists have warned that, if careful management of the use of these potent drugs is not carried out, pathogens can create defenses against them in a short time.”

Resistance to all antimicrobials is spreading faster than ever. For this reason, WHO considers this phenomenon as a serious public health problem worldwide.

 

A TEC STUDY TO REDUCE RESISTANCE

Motivated by the seriousness of this situation and its future repercussions on Mexicans and on the whole of humanity, Jaime Iván Castillo Silva, a student of Medicine at the School of Medicine and Health Sciences, and member of the American Society for Microbiology, developed a research and published the scientific article Antimicrobial synergy between mRNA targeted peptide nucleic acid and antibiotics in E. coli, where the high effectiveness of an original antimicrobial strategy, aimed at multi-resistant bacteria, and capable of reducing the emergence of the AMR.

Tecnológico de Monterrey
Jaime Iván Castillo Silva, student of the career of Medicine at the School of Medicine and Health Sciences, of the Tec de Monterrey. 
 

“This strategy consists in the development of synergistic combinatorial therapies between conventional antibiotics and antisense agents directed to bacterial RNA. The starting point was the effectiveness of traditional combinatorial therapies between conventional antibiotics, but the originality lies in the incorporation of an antimicrobial genomic technology: peptide nucleic acids”, Jaime explained in an interview for Transferencia Tec.

The foregoing means that antisense agents (synthetic polypeptides similar to DNA and RNA) were used to develop the study, which have the characteristic of attacking the bacteria by silencing their essential genes, modifying their genetic material and preventing some infections from continuing to attack.

“The synergistic therapies that we propose reduce the emergence of resistance due to two essential factors: its antigenic component and its combinatorial nature. In addition, they are able to reduce 87% of the minimum concentration of agents needed to inhibit the bacteria”, said the student.

He explained that this reduction in concentration could translate into considerably lower treatment costs than current ones, making it possible to implement them in developing countries, where the growth projections of antimicrobial resistance are more concerning.

“The results of the research allowed us to identify that the antibiotics Polymyxin B and Trimethoprim achieve synergy in combination with the PNA Anti-acpP molecule. By transferring this formula to pathological strains, the results were confirmed.

“The analyzes for both combinations (Polymyxin B – PNA Anti-acpP and Trimethoprim – PNA Anti-acpP) reported an index of fractional inhibitory concentration (FIC) of 0.375, value classified as highly synergistic even in the most conservative standardized scales”, is explained in the scientific article.

 

PASSION FOR BACTERIA

Tecnológico de Monterrey The young man from Tijuana discovered his passion for bacteria in 2014, when he was just 16 years old during a research stay at the University of Warsaw – one of the most prestigious institutions in Poland where a professor invited him to participate in one of his projects.

“That was my first contact with the subject of bacteria, and it was very cool because I learned to approach the bacteria from the most interesting part it has: its genetics. I went into the subject of the manipulation of its genes, and now I think I have a proper understanding of bacterial genetics, of their ability to produce genes and with them become resistant to antibiotics”, he recalled.

He says that it was in Warsaw where he met the “serious problem” of antimicrobial resistance, particularly antibiotics.

“Bacteria are the oldest organisms that have lived on our planet – way after human beings appeared. Therefore, they are very mature organisms, with a lot of experience, that have adapted and mutated. They are capable of transmitting genetic information horizontally and have been able to produce resistance genes, largely due to the overuse of antibiotics, so the balance that was there before, no longer exists”, he explained.

Antimicrobial resistance is a critical problem of the future that threatens to return humanity to a pre-antibiotic era, where a simple exposed wound could mean death.

“A future in which a person dies every three seconds due to intractable infections seems apocalyptic. However, it is a reality projected three decades before the threat of AMR”.

review commissioned by the UK government indicates that by 2050, a person will die every 3 seconds because of this problem. Great advances in medicine such as surgeries, organ transplants, cancer therapy or any other condition that exposes the body to bacteria, without antibiotics could be fatal”.

For this reason, the prospective development of his research is exciting. The identification of direct relationships between the mechanisms of action of the antibiotic Polymyxin B and the Anti-acpP agent represents a methodology with great potential for the discovery of new synergistic combinations that increase the possibilities to develop future therapies. In addition, it will allow discovering new mechanisms of action, now unknown, that could broaden the understanding of AMR.

“The solution only exists in the present; to invest now in research aimed at solving this problem is an imminent opportunity to avoid a biological contingency of global magnitude”, he warned.

And not least, Alexander Fleming, the discoverer of the first widely used antibiotic, penicillin, had already warned: “The misuse of antibiotics will make them obsolete”. Humanity has crossed that line and it is time to generate the antimicrobial strategies of tomorrow capable of making human resistance prevail over bacterial resistance, our survival depends on it.

--------------------------------------------------

Jaime Iván Castillo Silva is a student of Medicine, at the School of Medicine and Health Sciences, of Tec de Monterrey. He is a member of the American Society for Microbiology.
His scientific article Antimicrobial synergy between mRNA targeted peptide nucleic acid and antibiotics in E. coli was developed at the Center for New Technologies, University of Warsaw, in Poland, and was published as a student of the Tec de Monterrey in the Bioorganic and Medicinal Chemistry journal, in October 2018
For this research he was recognized as Citizen of the Year in Baja California and Young Researcher in the Walk of Fame of Tijuana, two initiatives that reward his great talents.