A team of Superior Council of Scientific Investigations (CSIC), through the Institute of Advanced Chemistry of Catalonia (IQAC), has designed a monoclonal antibody capable of neutralizing the toxin the most dangerous of one of the hospital bacteria that most concern the World Health Organization: Pseudomonas aeruginosaThis bacterium, very common in healthcare settings, has earned the label of "superbug" due to its ability to resist most available antibiotics.
The new antibody, called mAb122It does not seek to destroy the microorganism directly, but block pyocyanina key toxin that weakens the patient's defenses and promotes serious infections. This approach, known as an antivirulence strategy, is being considered as a possible way to reduce antibiotic use classics and curb the emergence of new resistances, a problem that has been raising alarms in hospitals in Spain and throughout Europe for years.
A bacterium prioritized by the WHO and a change in strategy
La Pseudomonas aeruginosa It is listed by the WHO as one of the most problematic pathogens globally due to its extraordinary capacity for adaptation and can lead to multidrug resistance. It is associated with respiratory, urinary, or surgical wound infections, especially in people with weakened immune systems or those hospitalized for extended periods.
In this context, the toxin pyocyanin plays a central role: this molecule damages cells of the immune systemIt alters the inflammatory response and allows the infection to persist and worsen. Neutralizing this toxin is therefore an indirect way to reduce the bacteria's potency without directly attacking it, something that traditional antibiotic treatments do and which, in the long run, promotes the selection of even more resistant strains.
The researcher from IQAC-CSIC Lluïsa Vilaplana Remember that the great adaptability of these superbugs makes it urgent to "promote new therapeutic strategies" that allow reduce multi-resistant strains and to slow the progression of infections. This priority is especially evident in intensive care units and other hospital services where vulnerable patients are concentrated.
The work, published in the journal ACS Pharmacology and Translational Science, it fits perfectly into this paradigm shift: an approach of antivirulence The aim is not to eliminate the bacteria, but to disable its main weapons of attack. This reduces the selective pressure associated with the intensive use of antibiotics, which is one of the driving forces behind the global antibiotic resistance crisis.
How the monoclonal antibody mAb122 works
The Nanobiotechnology for Diagnosis group of the IQAC-CSIC has generated in experimental mouse models a specific monoclonal antibody, named as mAb122A monoclonal antibody is a protein produced in the laboratory which recognizes with great precision a single target molecule; in this case, pyocyanin. This precision allows for highly selective blocking of its toxic effect.
Once obtained, the antibody was tested on macrophage culturesmAb122, a key type of immune system cell, was exposed to different concentrations of the bacterial toxin. The results indicate that mAb122 reduces cell damage caused by pyocyanin and significantly improves the survival of these defensive cells.
Furthermore, when the antibody was administered in the absence of toxin, no toxic effects were observed These effects are attributable to mAb122 itself, a relevant finding for future preclinical and clinical trials. This lack of toxicity is one of the essential requirements before proceeding to studies in complete animal models and, subsequently, in humans.
The researcher Pilar MarcoThe head of the team that led the study insists that the idea is not to kill the bacteria, but deactivate its virulence mechanismsBy "disarming" it in this way, the patient is protected and, at the same time, the strong evolutionary pressure exerted by broad-spectrum antibiotics, where the most resistant variants survive, is avoided.
Advantages of antivirulence over classic antibiotics
Antivirulence therapies, such as the one proposed with the mAb122 antibodyThey differ from conventional treatments because They do not affect the viability of the bacteriaInstead, they target specific virulence factors, in this case the pyocyanin toxin. By not attempting to eradicate the microorganism, the biological incentive for the bacteria to develop mutations that protect it against the drug is reduced.
This type of approach has several potential clinical advantagesOn the one hand, it could allow antibiotics to be used only when absolutely necessary, or in lower dosesThis reduces the risks associated with long and intensive treatments. Furthermore, it decreases the likelihood of generating new ones. multidrug-resistant strains, one of the biggest public health fears in Europe.
In practice, a treatment based on mAb122 would be considered as a companion tool rather than as a complete replacement for antibiotics. The goal would be to protect immune cells and keep the virulence of the infection under control, giving the patient's immune system—and, when necessary, other drugs—time to manage the clinical picture.
The authors of the study emphasize that this type of therapy could be especially useful in hospitalized patients with a high risk of infection by Pseudomonas aeruginosa, such as people with chronic respiratory diseases, cancer patients, or people undergoing complex surgical procedures.
Effects on the inflammatory response and next steps
In addition to analyzing the direct damage to immune cells, the IQAC-CSIC team evaluated how the antibody affected them. mAb122 to the inflammatory responsePyocyanin alters the production of various cytokines, molecules that regulate communication between cells of the immune system and the intensity of inflammation.
The tests showed that the antibody modified some of these levels of cytokines, suggesting that blocking the toxin could have a significant impact on how the body manages inflammation during infection. However, the researchers emphasize that further studies are needed to fully understand these variations and determine whether it is possible to adjust this inflammatory response in a beneficial way.
For now, the results obtained are in a phase vitroThat is, in cell cultures and experimental laboratory models. The next step will be to transfer this strategy to studies in vivo in animal models, essential to assess both the safety and efficacy of the antibody in whole organisms before considering human trials.
If the data are confirmed, the mAb122 approach could become established as a complementary therapeutic approach in the face of infections caused by multidrug-resistant bacteria, something especially relevant for European health systems, which have been warning for years about the increase in cases of resistant pathogens in the hospital environment.
With this development, the Nanobiotechnology for Diagnostics group at IQAC-CSIC contributes another piece to the puzzle in the fight against superbugs: a monoclonal antibody designed in Spain which, by deactivating the pyocyanin toxin of Pseudomonas aeruginosaIt aims to strengthen the patient's defenses, allow for a more rational use of antibiotics, and open the door to more specific and safe therapies against infections that currently pose a serious headache in hospitals.