Browsing by Author "Piña-Iturbe, A."

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    An inactivated SARS-CoV-2 vaccine is safe and induces humoral and cellular immunity against virus variants in healthy children and adolescents in Chile
    (2022) Soto, J.A.; Melo-González, F.; Gutierrez-Vera, C.; Schultz, B.M.; Berríos-Rojas, R.V.; Rivera-Pérez, D.; Piña-Iturbe, A.; Hoppe-Elsholz, G.; Duarte, L.F.; Vázquez, Y.; Moreno-Tapia, D.; Ríos, M.; Palacios, P.A.; Garcia-Betancourt, R.; Santibañez, Á.; Mendez, C.; Diethelm-Varela, B.; Astudillo, P.; Calvo, M.; Cárdenas, A.; González, M.; Goldsack, M.; Gutiérrez, V.; Potin, M.; Schilling, A.; Tapia, L.I.; Twele, L.; Villena, R.; Grifoni, A.; Sette, A.; Weiskopf, D.; Fasce, R.A.; Fernández, J.; Mora, J.; Ramírez, E.; Gaete-Argel, A.; Acevedo, M.; Valiente-Echeverría, F.; Soto-Rifo, R.; Retamal-Díaz, A.; Muñoz-Jofré, N.; Meng, X.; Xin, Q.; Alarcón-Bustamante, E.; González-Aramundiz, J.V.; Le Corre, N.; Álvarez, M.J.; González, P.A.; Abarca, K.; Perret, C.; Carreño, L.J.; Kalergis, A.M.; Bueno, S.M.
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    Bioinformatic and experimental characterization of SEN1998: a conserved gene carried by the Enterobacteriaceae-associated ROD21-like family of genomic islands
    (2022) Piña-Iturbe, A.; Hoppe-Elsholz, G.; Fernández, P.A.; Santiviago, C.A.; González, P.A.; Bueno, S.M.
    Genomic islands (GIs) are horizontally transferred elements that shape bacterial genomes and contributes to the adaptation to different environments. Some GIs encode an integrase and a recombination directionality factor (RDF), which are the molecular GI-encoded machinery that promotes the island excision from the chromosome, the first step for the spread of GIs by horizontal transfer. Although less studied, this process can also play a role in the virulence of bacterial pathogens. While the excision of GIs is thought to be similar to that observed in bacteriophages, this mechanism has been only studied in a few families of islands. Here, we aimed to gain a better understanding of the factors involved in the excision of ROD21 a pathogenicity island of the food-borne pathogen Salmonella enterica serovar Enteritidis and the most studied member of the recently described Enterobacteriaceae-associated ROD21-like family of GIs. Using bioinformatic and experimental approaches, we characterized the conserved gene SEN1998, showing that it encodes a protein with the features of an RDF that binds to the regulatory regions involved in the excision of ROD21. While deletion or overexpression of SEN1998 did not alter the expression of the integrase-encoding gene SEN1970, a slight but significant trend was observed in the excision of the island. Surprisingly, we found that the expression of both genes, SEN1998 and SEN1970, were negatively correlated to the excision of ROD21 which showed a growth phase-dependent pattern. Our findings contribute to the growing body of knowledge regarding the excision of GIs, providing insights about ROD21 and the recently described EARL family of genomic islands.
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    Horizontally acquired homologs of xenogeneic silencers: Modulators of gene expression encoded by plasmids, phages and genomic islands
    (2020) Piña-Iturbe, A.; Suazo, I.D.; Hoppe-Elsholz, G.; Ulloa-Allendes, D.; González, P.A.; Kalergis, A.M.; Bueno, S.M.
    Acquisition of mobile elements by horizontal gene transfer can play a major role in bacterial adaptation and genome evolution by providing traits that contribute to bacterial fitness. However, gaining foreign DNA can also impose significant fitness costs to the host bacteria and can even produce detrimental effects. The efficiency of horizontal acquisition of DNA is thought to be improved by the activity of xenogeneic silencers. These molecules are a functionally related group of proteins that possess affinity for the acquired DNA. Binding of xenogeneic silencers suppresses the otherwise uncontrolled expression of genes from the newly acquired nucleic acid, facilitating their integration to the bacterial regulatory networks. Even when the genes encoding for xenogeneic silencers are part of the core genome, homologs encoded by horizontally acquired elements have also been identified and studied. In this article, we discuss the current knowledge about horizontally acquired xenogeneic silencer homologs, focusing on those encoded by genomic islands, highlighting their distribution and the major traits that allow these proteins to become part of the host regulatory networks.
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    Inactivated Vaccine-Induced SARS-CoV-2 Variant-Specific Immunity in Children
    (2022) Soto, J.A.; Melo-González, F.; Gutierrez-Vera, C.; Schultz, B.M.; Berríos-Rojas, R.V.; Rivera-Pérez, D.; Piña-Iturbe, A.; Hoppe-Elsholz, G.; Duarte, L.F.; Vázquez, Y.; Moreno-Tapia, D.; Ríos, M.; Palacios, P.A.; Garcia-Betancourt, R.; Santibañez, Á.; Pacheco, G.A.; Mendez, C.; Andrade, C.A.; Silva, P.H.; Diethelm-Varela, B.; Astudillo, P.; Calvo, M.; Cárdenas, A.; González, M.; Goldsack, M.; Gutiérrez, V.; Potin, M.; Schilling, A.; Tapia, L.I.; Twele, L.; Villena, R.; Grifoni, A.; Sette, A.; Weiskopf, D.; Fasce, R.A.; Fernández, J.; Mora, J.; Ramírez, E.; Gaete-Argel, A.; Acevedo, M.L.; Valiente-Echeverría, F.; Soto-Rifo, R.; Retamal-Díaz, A.; Muñoz-Jofré, N.; Meng, X.; Xin, Q.; Alarcón-Bustamante, E.; González-Aramundiz, J.V.; Le Corre, N.; Álvarez-Figueroa, M.J.; González, P.A.; Abarca, K.; Perret, C.; Carreño, L.J.; Bueno, S.M.; Kalergis, A.M.
    Multiple vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been evaluated in clinical trials. However, trials addressing the immune response in the pediatric population are scarce. The inactivated vaccine CoronaVac has been shown to be safe and immunogenic in a phase 1/2 clinical trial in a pediatric cohort in China. Here, we report interim safety and immunogenicity results of a phase 3 clinical trial for CoronaVac in healthy children and adolescents in Chile. Participants 3 to 17 years old received two doses of CoronaVac in a 4-week interval until 31 December 2021. Local and systemic adverse reactions were registered for volunteers who received one or two doses of CoronaVac. Whole-blood samples were collected from a subgroup of 148 participants for humoral and cellular immunity analyses. The main adverse reaction reported after the first and second doses was pain at the injection site. Four weeks after the second dose, an increase in neutralizing antibody titer was observed in subjects relative to their baseline visit. Similar results were found for activation of specific CD4+ T cells. Neutralizing antibodies were identified against the Delta and Omicron variants. However, these titers were lower than those for the D614G strain. Importantly, comparable CD4+ T cell responses were detected against these variants of concern. Therefore, CoronaVac is safe and immunogenic in subjects 3 to 17 years old, inducing neutralizing antibody secretion and activating CD4+ T cells against SARS-CoV-2 and its variants. (This study has been registered at ClinicalTrials.gov under no. NCT04992260.) IMPORTANCE This work evaluated the immune response induced by two doses of CoronaVac separated by 4 weeks in healthy children and adolescents in Chile. To date, few studies have described the effects of CoronaVac in the pediatric population. Therefore, it is essential to generate knowledge regarding the protection of vaccines in this population. Along these lines, we reported the anti-S humoral response and cellular immune response to several SARS-CoV-2 proteins that have been published and recently studied. Here, we show that a vaccination schedule consisting of two doses separated by 4 weeks induces the secretion of neutralizing antibodies against SARS-CoV-2. Furthermore, CoronaVac induces the activation of CD4+ T cells upon stimulation with peptides from the proteome of SARS-CoV-2. These results indicate that, even though the neutralizing antibody response induced by vaccination decreases against the Delta and Omicron variants, the cellular response against these variants is comparable to the response against the ancestral strain D614G, even being significantly higher against Omicron.
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    L-Arginine Enhances Intracellular Killing of Carbapenem-Resistant Klebsiella pneumoniae ST258 by Murine Neutrophils
    (2020) Peñaloza, H.F.; Ahn, D.; Schultz, B.M.; Piña-Iturbe, A.; González, L.A.; Bueno, S.M.
    Carbapenem-resistant Klebsiella pneumoniae ST258 (CRKP-ST258) are a global concern due to their rapid dissemination, high lethality, antibiotic resistance and resistance to components of the immune response, such as neutrophils. Neutrophils are major host mediators, able to kill well-studied and antibiotic-sensitive laboratory reference strains of K. pneumoniae. However, CRKP-ST258 are able to evade neutrophil phagocytic killing, persisting longer in the host despite robust neutrophil recruitment. Here, we show that neutrophils are unable to clear a CRKP-ST258 isolate (KP35). Compared to the response elicited by a prototypic K. pneumoniae ATCC 43816 (KPPR1), the neutrophil intracellular response against KP35 is characterized by equivalent production of reactive oxygen species (ROS) and myeloperoxidase content, but impaired phagosomal acidification. Our results ruled out that this phenomenon is due to a phagocytosis defect, as we observed similar efficiency of phagocytosis by neutrophils infected with KP35 or KPPR1. Genomic analysis of the cps loci of KPPR1 and KP35 suggest that the capsule composition of KP35 explain the high phagocytosis efficiency by neutrophils. Consistent with other reports, we show that KP35 did not induce DNA release by neutrophils and KPPR1 only induced it at 3 h, when most of the bacteria have already been cleared. l-arginine metabolism has been identified as an important modulator of the host immune response and positively regulate T cells, macrophages and neutrophils in response to microbes. Our data show that l-arginine supplementation improved phagosome acidification, increased ROS production and enhanced nitric oxide consumption by neutrophils in response to KP35. The enhanced intracellular response observed after l-arginine supplementation ultimately improved KP35 clearance in vitro. KP35 was able to dysregulate the intracellular microbicidal machinery of neutrophils to survive in the intracellular environment. This process, however, can be reversed after l-arginine supplementation.