Publication: El potencial de los péptidos antimicrobianos de artrópodos como sustitutos de los antibióticos
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Date
2025-10-13
Authors
Cutillas Dólera, Pedro
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Escuelas::Escuela Internacional de Doctorado
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Galián Albadalejo, José ; Corrales Romero, Juan Carlos
Publisher
Universidad de Murcia
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DOI
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info:eu-repo/semantics/doctoralThesis
Description
Abstract
La resistencia bacteriana a los antibióticos se ha consolidado como una de las amenazas más serias para la salud pública global, al comprometer la eficacia de los tratamientos convencionales y provocar un aumento alarmante de la morbilidad, la mortalidad y los costes sanitarios. Esta situación se ha visto agravada por el uso indiscriminado de antibióticos tanto en medicina humana como veterinaria, la automedicación sin control médico, y la capacidad de las bacterias para intercambiar genes de resistencia mediante mecanismos de transferencia horizontal. Frente a este panorama, se ha intensificado la búsqueda de nuevas estrategias terapéuticas, entre las que destacan los péptidos antimicrobianos (AMPs) como una alternativa viable y prometedora.
Los AMPs son pequeñas proteínas que presentan actividad frente a una amplia variedad de patógenos, incluyendo bacterias, hongos, virus e incluso células tumorales. Estas moléculas destacan por ser termoestables, poco tóxicas para células eucariotas y por actuar mediante mecanismos distintos a los antibióticos tradicionales, lo que reduce significativamente la probabilidad de aparición de resistencias. Aunque se han identificado AMPs en diversos grupos de organismos, los artrópodos se presentan como una fuente especialmente interesante debido a su diversidad biológica y a su constante exposición a entornos microbianos hostiles.
El presente trabajo comenzó con el análisis de la microbiota intestinal de dos especies de insectos: Periplaneta americana y Zophobas morio, criadas en el insectario de la Universidad de Murcia y en la empresa spin-off Arthropotech SL. El objetivo fue detectar comunidades bacterianas con perfiles de multirresistencia. Los resultados revelaron una elevada presencia de comunidades bacterianas resistentes a múltiples antibióticos, algunas de las cuales podrían tener implicaciones para la salud humana, dada su proximidad ecológica a entornos urbanos y domésticos. Este hallazgo motivó la búsqueda de nuevas estrategias terapéuticas alternativas.
A partir de estos hallazgos, se dirigieron los esfuerzos hacia la identificación y validación experimental de AMPs en distintos artrópodos. En el escarabajo tigre Calomera littoralis se identificaron péptidos como CliCecB2 y Clit-Def, que mostraron eficacia frente a bacterias Gram + y Gram -. Paralelamente, se realizaron estudios bioinformáticos sobre los genomas de Tuta absoluta y Hermetia illucens, que permitieron predecir nuevas secuencias candidatas a AMPs. Estas fueron posteriormente sintetizadas y evaluadas in vitro, confirmando su capacidad para inhibir el crecimiento de bacterias multirresistentes.
Además, se exploró el potencial terapéutico del veneno de escorpiones, tradicionalmente asociado con toxicidad. Se centró la atención en péptidos sin puentes disulfuro (NDBP), los cuales fueron sintetizados y sometidos a ensayos in vitro frente a cepas bacterianas resistentes. Los resultados mostraron una actividad antimicrobiana destacada.
En conjunto, este trabajo ofrece una visión integral del problema de la multirresistencia bacteriana y de los esfuerzos experimentales realizados para identificar soluciones innovadoras. Los resultados obtenidos respaldan el uso de artrópodos como una fuente prometedora de compuestos antimicrobianos, y posicionan a los AMPs derivados de insectos y escorpiones como herramientas valiosas para afrontar uno de los principales desafíos de la medicina actual.
Bacterial resistance to antibiotics has emerged as one of the most serious threats to global public health, as it compromises the effectiveness of conventional treatments and leads to an alarming increase in morbidity, mortality, and healthcare costs. This situation has been exacerbated by the indiscriminate use of antibiotics in both human and veterinary medicine, self-medication without medical supervision, and the ability of bacteria to exchange resistance genes through horizontal gene transfer mechanisms. In response to this scenario, the search for new therapeutic strategies has intensified, with antimicrobial peptides (AMPs) standing out as a viable and promising alternative. AMPs are small proteins with activity against a wide variety of pathogens, including bacteria, fungi, viruses, and even tumor cells. These molecules are notable for being thermostable, minimally toxic to eukaryotic cells, and for acting through mechanisms different from traditional antibiotics, which significantly reduces the likelihood of resistance emerging. Although AMPs have been identified in various groups of organisms, arthropods represent an especially interesting source due to their biological diversity and constant exposure to hostile microbial environments. This study began with the analysis of the gut microbiota of two insect species: Periplaneta americana and Zophobas morio, reared at the insectary of the University of Murcia and the spin-off company Arthropotech SL. The aim was to detect bacterial communities with multidrug resistance profiles. The results revealed a high presence of bacterial communities resistant to multiple antibiotics, some of which could have implications for human health due to their ecological proximity to urban and domestic environments. This finding motivated the search for alternative therapeutic strategies. Based on these findings, efforts were directed toward the identification and experimental validation of AMPs in different arthropods. In the tiger beetle Calomera littoralis, peptides such as CliCecB2 and Clit-Def were identified, showing efficacy against both Gram-positive and Gram-negative bacteria. In parallel, bioinformatic studies were conducted on the genomes of Tuta absoluta and Hermetia illucens, which allowed the prediction of new candidate AMP sequences. These were later synthesized and evaluated in vitro, confirming their ability to inhibit the growth of multidrug-resistant bacteria. In addition, the therapeutic potential of scorpion venom, traditionally associated with toxicity, was explored. Attention was focused on non-disulfide-bridged peptides (NDBPs), which were synthesized and subjected to in vitro assays against resistant bacterial strains. The results showed remarkable antimicrobial activity. Overall, this work provides a comprehensive view of the problem of bacterial multidrug resistance and the experimental efforts made to identify innovative solutions. The results support the use of arthropods as a promising source of antimicrobial compounds and position AMPs derived from insects and scorpions as valuable tools to address one of the main challenges in modern medicine.
Bacterial resistance to antibiotics has emerged as one of the most serious threats to global public health, as it compromises the effectiveness of conventional treatments and leads to an alarming increase in morbidity, mortality, and healthcare costs. This situation has been exacerbated by the indiscriminate use of antibiotics in both human and veterinary medicine, self-medication without medical supervision, and the ability of bacteria to exchange resistance genes through horizontal gene transfer mechanisms. In response to this scenario, the search for new therapeutic strategies has intensified, with antimicrobial peptides (AMPs) standing out as a viable and promising alternative. AMPs are small proteins with activity against a wide variety of pathogens, including bacteria, fungi, viruses, and even tumor cells. These molecules are notable for being thermostable, minimally toxic to eukaryotic cells, and for acting through mechanisms different from traditional antibiotics, which significantly reduces the likelihood of resistance emerging. Although AMPs have been identified in various groups of organisms, arthropods represent an especially interesting source due to their biological diversity and constant exposure to hostile microbial environments. This study began with the analysis of the gut microbiota of two insect species: Periplaneta americana and Zophobas morio, reared at the insectary of the University of Murcia and the spin-off company Arthropotech SL. The aim was to detect bacterial communities with multidrug resistance profiles. The results revealed a high presence of bacterial communities resistant to multiple antibiotics, some of which could have implications for human health due to their ecological proximity to urban and domestic environments. This finding motivated the search for alternative therapeutic strategies. Based on these findings, efforts were directed toward the identification and experimental validation of AMPs in different arthropods. In the tiger beetle Calomera littoralis, peptides such as CliCecB2 and Clit-Def were identified, showing efficacy against both Gram-positive and Gram-negative bacteria. In parallel, bioinformatic studies were conducted on the genomes of Tuta absoluta and Hermetia illucens, which allowed the prediction of new candidate AMP sequences. These were later synthesized and evaluated in vitro, confirming their ability to inhibit the growth of multidrug-resistant bacteria. In addition, the therapeutic potential of scorpion venom, traditionally associated with toxicity, was explored. Attention was focused on non-disulfide-bridged peptides (NDBPs), which were synthesized and subjected to in vitro assays against resistant bacterial strains. The results showed remarkable antimicrobial activity. Overall, this work provides a comprehensive view of the problem of bacterial multidrug resistance and the experimental efforts made to identify innovative solutions. The results support the use of arthropods as a promising source of antimicrobial compounds and position AMPs derived from insects and scorpions as valuable tools to address one of the main challenges in modern medicine.
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