Carlos Alberto Guzmán

Spanish National Research Council, Madrid, Madrid, Spain

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Publications (4)31.16 Total impact

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    Article: In vivo gene regulation in Salmonella spp. by a salicylate-dependent control circuit.
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    ABSTRACT: Systems allowing tightly regulated expression of prokaryotic genes in vivo are important for performing functional studies of bacterial genes in host-pathogen interactions and establishing bacteria-based therapies. We integrated a regulatory control circuit activated by acetyl salicylic acid (ASA) in attenuated Salmonella enterica that carries an expression module with a gene of interest under control of the XylS2-dependent Pm promoter. This resulted in 20-150-fold induction ex vivo. The regulatory circuit was also efficiently induced by ASA when the bacteria resided in eukaryotic cells, both in vitro and in vivo. To validate the circuit, we administered Salmonella spp., carrying an expression module encoding the 5-fluorocytosine-converting enzyme cytosine deaminase in the bacterial chromosome or in a plasmid, to mice with tumors. Induction with ASA before 5-fluorocytosine administration resulted in a significant reduction of tumor growth. These results demonstrate the usefulness of the regulatory control circuit to selectively switch on gene expression during bacterial infection.
    Nature Methods 12/2007; 4(11):937-42. · 19.28 Impact Factor
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    Article: Phylogenetic analysis of previously nontypeable hepatitis C virus isolates from Argentina.
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    ABSTRACT: Phylogenetic analysis of hepatitis C virus isolates from Argentina that were previously nontypeable by restriction fragment length polymorphism (RFLP) analysis revealed that they belong to genotype 1a. A substitution at position 107 (G-->A), which is the landmark of these strains, was shown to be distributed among isolates worldwide. The RFLP patterns obtained for these isolates should be added to the ones reported for genotype 1 isolates.
    Journal of Clinical Microbiology 06/2006; 44(6):2229-32. · 4.15 Impact Factor
  • Article: Hepatitis C virus isolates from Argentina disclose a novel genotype 1-associated restriction pattern.
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    ABSTRACT: Hepatitis C virus isolates which disclosed a novel genotype 1-associated restriction pattern by restriction fragment length polymorphism analysis were characterized. Except for a mother and child pair, the patients were unrelated. Sequence analysis showed a G-->A substitution leading to a new RsaI recognition site. Phylogenetic analysis revealed that these isolates constitute a novel genetic lineage within the main cluster of genotype 1 strains.
    Journal of Clinical Microbiology 04/2004; 42(3):1298-301. · 4.15 Impact Factor
  • Article: Genetic immunization: bacteria as DNA vaccine delivery vehicles.
    Pablo Daniel Becker, Miriam Noerder, Carlos Alberto Guzmán
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    ABSTRACT: The so-called DNA vaccination represents one of the most notable tools under development in the field of vaccinology. The concept of administering the gene coding for any given protective antigen and make responsible vaccinee's own cells to produce the protein appeals as too simple to be true. Indeed, the implementation of this approach for mass vaccination should overcome several bottlenecks, such as need of high dosages and poor immunogenicity. In this context, the use of live attenuated bacteria as delivery system for plasmid DNA has emerged as a promising alternative to overcome many of those pitfalls. In addition, this approach is not only amenable for mucosal administration, but allows to specifically target professional antigen presenting cells. This results in their transfection, as well as in their activation and maturation, due to their built-in adjuvant properties resulting from the stimulation of pattern recognition receptors. This chapter discusses the specific features that should be taken into consideration when designing a plasmid vector, current candidate bacterial carriers for DNA delivery and main safety issues.
    Human vaccines 4(3):189-202. · 3.58 Impact Factor