Person:
Maffia, Paulo César

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1976
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Laboratorio de Aplicaciones Biotecnológicas y Microbiología (LAByM)
El Laboratorio de Aplicaciones Biotecnológicas y Microbiología (LABYM) está especializado en cannabis y sus aplicaciones para combatir bacterias y virus. Líneas de investigación 1. Obtención y caracterización de nuevos péptidos antimicrobianos y antivirales 2. Cannabis medicinal: evaluación de cannabidiol como antimicrobiano. 3. Desarrollo y obtención de nuevas moléculas bioactivas a partir de plantas medicinales y aromáticas utilizando plataformas biotecnológicas (Mejoramiento y Micropropagación de Cannabis sativa). 4. Desarrollo de biofertilizantes para promoción del crecimiento y salud de la Cannabis sativa.
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Investigador
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Maffia
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Paulo César
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    Publication
    On the Offensive: The Role of Outer Membrane Vesicles in the Successful Dissemination of New Delhi Metallo-b-lactamase (NDM-1)
    (American Society for Microbiology, 2021-09) Martínez, Melina María Belén; Bonomo, Robert A.; Vila, Alejandro José; González, Lisandro Javier; Maffia, Paulo César
    The emergence and worldwide dissemination of carbapenemase-producing Gram-negative bacteria are a major public health threat. Metallo-b-lactamases (MBLs) represent the largest family of carbapenemases. Regrettably, these resistance determinants are spreading worldwide. Among them, the New Delhi metallo-b-lactamase (NDM-1) is experiencing the fastest and largest geographical spread. NDM-1 b-lactamase is anchored to the bacterial outer membrane, while most MBLs are soluble, periplasmic enzymes. This unique cellular localization favors the selective secretion of active NDM-1 into outer membrane vesicles (OMVs). Here, we advance the idea that NDM-containing vesicles serve as vehicles for the local dissemination of NDM-1. We show that OMVs with NDM-1 can protect a carbapenem-susceptible strain of Escherichia coli upon treatment with meropenem in a Galleria mellonella infection model. Survival curves of G. mellonella revealed that vesicle encapsulation enhances the action of NDM-1, prolonging and favoring bacterial protection against meropenem inside the larva hemolymph. We also demonstrate that E. coli cells expressing NDM-1 protect a susceptible Pseudomonas aeruginosa strain within the larvae in the presence of meropenem. By using E. coli variants engineered to secrete variable amounts of NDM-1, we demonstrate that the protective effect correlates with the amount of NDM-1 secreted into vesicles. We conclude that secretion of NDM-1 into OMVs contributes to the survival of otherwise susceptible nearby bacteria at infection sites. These results disclose that OMVs play a role in the establishment of bacterial communities, in addition to traditional horizontal gene transfer mechanisms. IMPORTANCE Resistance to carbapenems, last-resort antibiotics, is spreading worldwide, raising great concern. NDM-1 is one of the most potent and widely disseminated carbapenem-hydrolyzing enzymes spread among many bacteria and is secreted to the extracellular medium within outer membrane vesicles. We show that vesicles carrying NDM-1 can protect carbapenem-susceptible strains of E. coli and P. aeruginosa upon treatment with meropenem in a live infection model. These vesicles act as nanoparticles that encapsulate and transport NDM-1, prolonging and favoring its action against meropenem inside a living organism. Secretion of NDM-1 into vesicles contributes to the survival of otherwise susceptible nearby bacteria at infection sites. We propose that vesicles play a role in the establishment of bacterial communities and the dissemination of antibiotic resistance, in addition to traditional horizontal gene transfer mechanisms.
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    Publication
    Review of antiviral peptides for use against zoonotic and selected non-zoonotic viruses
    (Elsevier Science, 2021) Hollmann, Axel; Cardoso, Nancy Patricia; Espeche, Juan Carlos; Maffia, Paulo César
    Viruses remain one of the leading causes of animal and human disease. Some animal viral infections spread sporadically to human populations, posing a serious health risk. Particularly the emerging viral zoonotic diseases such as the novel, zoonotic coronavirus represent an actual challenge for the scientific and medical community. Besides human health risks, some animal viral infections, although still not zoonotic, represent important economic loses to the livestock industry. Viral infections pose a genuine concern for which there has been an increasing interest for new antiviral molecules. Among these novel compounds, antiviral peptides have been proposed as promising therapeutic options, not only for the growing body of evidence showing hopeful results but also due to the many adverse effects of chemical-based drugs. Here we review the current progress, key targets and considerations for the development of antiviral peptides (AVPs). The review summarizes the state of the art of the AVPs tested in zoonotic (coronaviruses, Rift Valley fever viruses, Eastern Equine Encephalitis Virus, Dengue and Junín virus) and also non-zoonotic farm animal viruses (avian and cattle viruses). Their molecular target, amino acid sequence and mechanism of action are summarized and reviewed. Antiviral peptides are currently on the cutting edge since they have been reported to display anti-coronavirus activity. Particularly, the review will discuss the specific mode of action of AVPs that specifically inhibit the fusion of viral and host-cell membranes for SARS-CoV-2, showing in detail some important features of the fusion inhibiting peptides that target the spike protein of these risky viruses