A monoclonal antibody created by the Nanobiotechnology for Diagnostics group (Nb4D) at the Institute of Advanced Chemistry of Catalonia (IQAC), part of the Spanish National Research Council (CSIC), has demonstrated in cell cultures that it can neutralize the toxin pyocyanin produced by the bacterium Pseudomonas aeruginosa, which the World Health Organization considers highly dangerous due to its strong resistance to nearly all antibiotics and its prevalence in hospital settings.
In this study, published in the journal ACS Pharmacology and Translational Science, the researchers followed an "anti-virulence" strategy. Unlike current treatments that target the bacterium itself, this approach focuses on inhibiting the toxin pyocyanin, with the added advantage that it would not promote antibiotic resistance.
Pseudomonas aeruginosa is regarded as one of the most concerning pathogens worldwide because of its ability to adapt and develop resistance to most available antibiotics, causing thousands of deaths each year among vulnerable patients. Its toxin, pyocyanin, plays a key role in its harmful capacity, as it kills immune system cells and disrupts the body's inflammatory response. Neutralizing this toxin represents an alternative therapeutic strategy with the potential to reduce the need for antibiotics and the risk of new resistances emerging.
Lluïsa Vilaplana, IQAC-CSIC researcher and lead author of the study, stresses the urgency of finding innovative treatments against this type of bacterium. "Due to its high adaptability, this bacterium has developed strong resistance to conventional antibiotics, which has driven the development of new therapeutic strategies to reduce multidrug-resistant strains and minimize infection progression," she explains. This extreme resistance makes the search for alternatives a top priority challenge.
Monoclonal antibody
With this objective, the researchers at IQAC developed, in mouse models, a monoclonal antibody named mAb122, designed to specifically bind to pyocyanin and prevent its action. A monoclonal antibody is a laboratory-generated protein that recognizes a single molecule with very high precision, allowing its effect to be selectively blocked. After its production, the antibody was evaluated in macrophages exposed to different concentrations of the toxin. The results showed that mAb122 reduces the cellular damage caused by pyocyanin and significantly increases the survival of immune cells. Moreover, when administered alone, it showed no toxic effects, an essential aspect for considering its further development.
IQAC researcher Pilar Marco, head of the Nanobiotechnology for Diagnostics group, which led the study, highlights the potential of this therapeutic approach. "Unlike conventional antibiotics, this strategy does not aim to directly eliminate the microorganism, but rather to neutralize one of its main virulence mechanisms. With this type of anti-virulence therapy, selective pressure that favors the emergence of resistance is reduced." This form of intervention seeks to disarm the bacterium instead of killing it, thereby decreasing the likelihood of antibiotic-resistance mutations.
The study proposes an innovative and promising therapeutic approach aimed at minimizing antibiotic use and allowing lower doses. By not acting on bacterial viability but on one of its main virulence mechanisms, the antibody does not exert selective pressure, reducing the probability of new resistances emerging.
The study also analyzed how the antibody affected the inflammatory response, as pyocyanin alters the production of various cytokines involved in immune regulation. Although the antibody modified some of these levels, the results indicate that its impact on inflammation will need to be studied more thoroughly, and it will be necessary to determine whether it can be appropriately modulated in future research stages.
Neutralization of pyocyanin through antibodies therefore represents a promising strategy to protect, at the cellular level, the body's defensive cells against one of the main virulence factors of Pseudomonas aeruginosa. This approach does not seek to eliminate the bacterium, but rather to reduce its ability to cause damage and facilitate the action of the immune system, which could be decisive in preventing severe infections without increasing antibiotic use.
Although the work is still at an early stage, the in vitro results pave the way for future in vivo studies, which are necessary to evaluate safety and efficacy in whole organisms. If these investigations confirm the findings, this approach could become a more specific and safer therapeutic tool to combat infections caused by multidrug-resistant bacteria, especially in hospital settings. The next step will be to evaluate its protective effect in animal models and determine whether unwanted inflammatory responses can be avoided.
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